GVN 2020 Special Annual Meeting Executive Summary

A New Era in the Fight Against COVID-19 Pandemic: Forging a “Viral Pandemic Readiness Alliance”

A September 22-23, 2020 Special Meeting of Top Global Experts Launches “Global Virus Network’s Vision for Future Pandemic Preparedness”

We are in the midst of a pandemic that has completely upended the world with major economic, social and psychological impacts. The major threat to public health is not only connected to COVID-19-related mortalities, but also to associated morbidity and, possibly, sequelae; moreover COVID-19 impacts overall population health due to the disorganization of health systems.

We must be very humble, as we cannot predict what the future could hold: seasonal variations? Long term persistence? Or regression? We need to keep in mind that the reason behind the SARS-CoV-1 epidemic’s regression has remained in part mysterious. In fact, eradication of the virus seems impossible, and herd immunity may be very difficult to achieve. Thus, we must learn to live with the virus.

It is increasingly clearer that we are not facing “another health crisis.” We are entering a new era where novel modes of organization must be designed. We cannot wait for the current crisis to conclude to prepare for the next—we must act now!

Despite significant progress in global health following previous epidemics and pandemics (including HIV, Influenza and Ebola), and although we were aware of the potential risk of such new pandemics, we were not sufficiently prepared. There are two immediate consequences for global health policies:

  • The importance of infectious diseases, global and “one health” are only further emphasized.
  • The divergence between politics and health in many countries has led to disastrous decisions. As such, we need to provide governing leaders with science-driven and independent strategies.

The Global Virus Network (GVN) is poised to be an important partner in achieving these objectives. This is a coalition of the foremost virologists worldwide, representing 57 research centers and 10 affiliates in 33 countries, and growing by the day. The GVN coordinates scientific projects and has organized task forces on specific viruses including Zika, Chikungunya, and HTLV-1, and now SARS-CoV-2. The organization also has a major focus on education, training and mentoring others in the field. Globally, there is a lack of critical mass in scientists, medical doctors and public health professionals working on infectious diseases. The GVN plays a significant role in advocacy and providing statements (in particular through its website https://gvn.org/). Science-driven and independent expertise are key drivers of meaningful public health strategies, and through its network of outstanding virologists worldwide, GVN offers national and international institutions, as well as industrial partners, a unique source of information and recommendations.

In this context, the GVN organized a two-day workshop dedicated to COVID-19 and future pandemic preparedness with the aim to evaluate what has been improperly and properly handled during these first eight months of the COVID-19 pandemic spreading. The workshop looked at precisely identifying the challenges ahead, the actions to take and how the GVN can collaborate with the many institutions to meet these needs. The goal of the workshop was not to revisit in detail all topics and known facts.  A video of the full post-meeting press conference, can be found here.

The following summarizes the major issues discussed:

1) Preparedness: We were not prepared, and we need to prepare now; This implies novel organizational modalities.

  • Cooperation and coordination, beyond goodwill and fashionable wordings; too many institutions are still working in silos with self-interest strategies.
  • Leverage technologic innovation and scientific progress to produce diagnostics, vaccines, and therapeutics.
  • Contemplate and implement novel modes of interactions between academics and industrials, and such partnerships have been at the heart of the GVN since its inception.
  • Multi- and transdisciplinary collaborations, including social and behavioral sciences, and perception of communication.
  • International collaborations: one country alone cannot solve the problem. While this seems obvious, most countries have reacted on an isolated basis. A global collaboration network for pandemic preparedness and prevention needs to be implemented immediately.

2) Prediction: Humans are the best sentinels. Is it feasible to predict future pandemics? How to sufficiently organize surveillance?

  • We must recognize that we cannot predict future pandemics, though we can improve our strategies. Yet, we have sufficient technologies and data analysis systems (including artificial intelligence), but we need to establish implementation and global data sharing mechanisms.
  • We know that animal viruses are major risk factors for the next epidemics and pandemics. This is even increasingly at stake. During the meeting scientists emphasized that five of the seven human coronaviruses identified (229E, NL63, OC43, HKU1, SARS-CoV-1, MERS-CoV and SARS-CoV-2) in the last 20 years have emerged from bats. Humans are modifying ecosystems and are in fact accelerating transmission events.
  • Comprehensive sequencing-based analysis of all viruses worldwide (“animal viromes”) provides useful knowledge but does not predict transmission to humans. GVN scientists point to the importance of focusing surveillance efforts to the human populations who interface with animals.

3) Origin: There is no scientific evidence that SARS-CoV-2 was disseminated by human manipulation.

  • GVN scientists all concur on this controversy.
  • The mission to find out the origins of the virus was a true international collaboration and transparent process featuring scientists from China, America, Australia, Japan, France, and the Philippines.
  • There is a 1,200-nucleotide difference between the closest backbone virus and SARS-CoV-2, representing 4 to the power of 1,200 possible combinations. Even if someone had unlimited research funding and all the best virologists in the world, no one could make this virus.
  • An extensive study will be conducted starting in China and through Southeast Asia to identify the origins of the virus and to allow much better surveillance and mitigation for future emerging viruses.

4) Transmission: “Super spreaders” and “super spreading” events are major drivers of pandemics.

  • COVID-19 is a highly contagious respiratory disease with very low mortality directly induced by the virus, thus the ideal condition for a virus to spread. The importance of masks, physical distancing and handwashing is well-known. GVN scientists also emphasize the importance of research on disinfectants, an underappreciated protective measure.
  • As re-emphasized in this workshop, only a handful of those infected seem highly contagious. Thus, transmission is driven by a limited number of individuals who behave as “super spreaders.” Why do some individuals (a.k.a. “super spreaders”) transmit viruses to so many others? Although we know that such individuals show high viral load and are generally, yet not always, younger, this cannot fully account for this spreading. What are the other factors? Thus far, research focused on such individuals is mandatory. The question remains whether we can identify novel biomarkers, though we would need to fully exclude stigmatization.
  • Also, this implies for obvious statistical reasons that large gatherings are major risk factors for being in contact with such rare “super spreaders” and thus contributors to rapid viral wide spreading. Therefore, we should not only speak of “super spreaders” but also of “super spreading” events.
  • Aerosol-related transmission is still a controversial issue. Yet, GVN scientists have emphasized that the impact of short-range aerosol-driven transmission contributes to the dissemination of the virus, particularly in the context of “super spreading” events. Masks are very efficient against large droplets but are unfortunately less efficient against such aerosols.

5) Diagnostic: Efficient and rapid diagnostic testing is the key for controlling an infectious disease, and we have not benefited enough from the huge technology progress in this area.

  • Nothing is needed more than rapid diagnostic tests. We need to trace and follow infected individuals and their contacts. We need to educate the general public. This is absolutely the foundation, and we cannot do anything without it.
  • There is now ample evidence that salivary sampling can be used instead of nasal swabs in both symptomatic and asymptomatic infected individuals. This can overhaul access to testing, in particular but not only in children. Rapid tests, whether molecular or immune-based, are now available at a low cost, and presentations have been made by GVN scientists demonstrating these points. Point-of-care rapid tests should also be available.
  • Important progress has been made regarding serological assays, offering major insights not only on the epidemiology but also defining the neutralization capacity of detected antibodies as novel correlates for protection. These are fully necessary for evaluating protective measures, novel therapies and vaccines. As an example, some presentations showed that the nature of the antibodies to SARS-CoV-2 significantly differs when comparing children and elderly, possibly accounting for variations in disease severity. Yet, we need standardized protocols for neutralizing assays. Also, the protective efficacy of antibodies needs to be further substantiated. GVN scientists have emphasized the need to get access to the cellular immune response for delineating such correlates of protection.
  • Discussions have been focused on how we should provide novel organizational schemes to favor rapid translation from technology-driven research to routine testing, and partnerships between academic and industrial partners should be reinforced in an international context. Institutions such as the Coalition for Epidemic Preparedness and Innovations created for vaccine development are interesting models to get such novel consortia moving faster.

6) Therapeutics: Despite a huge effort made on drug repurposing so far, we have achieved limited results.

  • Drug repurposing must continue to be at the heart of the therapeutic strategy, providing immediate access of well characterized molecules and allowing massive screening for antiviral activities. However, we do not yet have access to drugs that can prevent transmission in high-risk groups or treat early infections. In fact, we are left with combining steroids, Remdesivir (with some but limited efficacy) and anticoagulants for severe infections with pneumonia. Though, several ongoing studies offer hope for novel prophylactic and early treatment molecules.
  • In this context, GVN scientists have emphasized the need for research agencies to fund not only drug repurposing but also drug discovery. Drug discovery will take time to lead to novel accessible molecules – this is a long battle and not a single crisis.
  • Several presentations demonstrated the potential of novel therapeutic avenues, from immunomodulatory to direct antiviral approaches. Antivirals are only meaningful in the early phase of the infection.
  • The trend will be to use drugs targeting multiple pathways and to combine antivirals and immunomodulatory molecules. Additionally, GVN scientist are addressing the possibility of developing broad spectrum antivirals, which could be effective against coronaviruses, influenza and filoviruses (involved in hemorrhagic fevers such as Ebola, Zika etc.).

7) Vaccines: Safety, efficacy and durability are predominant concerns of COVID-19 vaccine development. Nonspecific immunization procedures must be considered along with COVID-19-specific vaccines.

  • Enormous parallel efforts are being made worldwide utilizing innovative approaches to shorten the vaccine development time. There is uncertainty as to when vaccines for COVID-19 will be readily available for mass vaccination and which formula will be the most efficient. Importantly, we need to ensure the safety of vaccines by testing proper animal models and complying with regulatory requirements – we simply cannot incur adverse reactions.
  • We also need second-generation vaccines that are more focused on the cell immune response.
  • Stimulation of the Innate immune response by non-specific immunization, for example: Bacille Calmette-Guérin (BCG), Oral Polio Virus, is extremely important. GVN scientists made important presentations on this topic, illustrating how BCG-based strategies have already allowed in different contexts to decrease the neonates’ overall mortality in Africa and the rate of respiratory infections in elderly. Mechanisms accounting for stimulation of innate immune response in COVID-19 were thoroughly discussed, and ongoing trials on the impact of BCG and Oral Polio Virus-based vaccines on COVID-19 were deliberated. This approach is complementary to specific vaccine development and might offer a bridge before getting an efficient and sufficiently characterized vaccine.

Conclusions:

It is not a crisis – it is a new era. We have major challenges ahead.  We need a new organization and we need it now.  This is where the GVN is very important, and complementary to national and international agencies. This workshop has led GVN to forge a unified and multidisciplinary pandemic response strategy, tentatively named the Viral Pandemic Readiness Alliance (VPRA) by collaborations with university, industry, government and communities to merge the efforts and find solutions together.

  • True international collaborations are essential and go beyond good and fashionable wordings. Global, One Health and VPRA strategy can support future pandemic preparedness with distribution of diagnostics, vaccine and therapeutics and other interventional measures.
  • In a surge of COVID-19 publications and news releases, we need reliable channels for dissemination of scientific knowledge and information sharing. GVN and VPRA can contribute to this global collaboration effort by assisting the UN, WHO, CEPI, Wellcome Trust, the Bill and Melinda Gates Foundation, and other organizations to serve this purpose.

 

GVN 2020 Meeting Press Release

GVN International Press Conference September 24, 2020

GVN’s Top Virus Experts Meet Together To Identify Most Promising Advances To Battle COVID-19 & Strategies To Prepare For Future Pandemics

Rapid Diagnostic Testing, Repurposing Drug Therapies and Vaccines Targeting Innate Immunity, Are Integral Factors in Mitigating COVID-19

Baltimore, Maryland, USA, September 30, 2020: The Global Virus Network (GVN), a coalition of the world’s leading medical and basic virology research centers working to prevent illness and death from viral disease, convened a press conference with attendees from across the globe to discuss key takeaways from the GVN virtual 2020 Special Annual Meeting held September 23-24, 2020.

A video of the full press conference, can be found here.

“We do not know what the future holds for COVID-19 – there may be seasonal variations or chronic infections or maybe a slowdown,” said Dr. Christian Bréchot, GVN President. “However, we know that we have to prepare and that this for now and not after the end of this pandemics; in the spirit of preparation, it is very timely that we used the Special Annual Meeting to band together international experts to identify and analyze what went wrong, what has been properly handled and what recommendations we can confidently make.”

Key findings during the meeting regarding SARS-CoV-2 and COVID-19 research include:

  • “Super-spreaders” and “super-spreading” events are major drivers of the pandemic, indicating that only a handful of those infected seem be exponentially contagious. Further, short-range aerosol-driven transmission contributes to the dissemination of the virus, particularly in the context of the super spreading events.
  • Key pandemic response strategies – the need to take better advantage of the major technology progress in diagnostics, a key driver for the control of infectious diseases; salivary sampling will very much increase our testing capacity, including in school settings; novel rapid and cheap molecular rapid diagnostic tests combined with digital-based transmission of the results, tracing and isolation should be widely emphasized, an understanding of communicability and transmission and, most importantly, the creation of a unified and multidisciplinary response with mechanisms for information sharing among international virologists and independent authorities.
  • An evaluation of vaccine development – timing, an analysis of the candidates, side-effects and managing the world’s expectation for a satisfactory and timely vaccine. Until a classical, effective vaccine is available, vaccines that stimulate the body’s innate immune system, such as the oral polio vaccine and BCG, are integral in protecting against infection.
  • A very strong statement against SARS-CoV-2 being the result of human manipulation.
  • An update on the available and future therapies, emphasizing the need to combine novel antiviral and immunomodulatory molecules as well as the need to contemplate in the future antivirals with broad spectrum against several viruses.

Dr. Bréchot, who also is a professor at the University of South Florida in Tampa, continued, “This is not just a crisis – it is a new era. We have major challenges ahead, we need a new organization and we need it now.  Global collaborations will build a strong foundation. This is where the GVN is very important, and complementary to national and international agencies. The GVN is well positioned to establish with all partners a Viral Pandemic Readiness Alliance to facilitate collaborations with universities, industry, governments and communities to merge efforts and find solutions together.”

“Simple, safe, oral, inexpensive, live vaccines such as the oral polio vaccine (OPV) will have a broad benefit against COVID-19. This can also likely be used in future pandemics, particularly of respiratory viruses, by inducing innate immunity, which is immediate and not as limiting as a specific vaccine,” said Dr. Robert Gallo, co-founder of GVN; The Homer & Martha Gudelsky Distinguished Professor in Medicine, co-founder and director of the Institute of Human Virology at the University of Maryland School of Medicine.

Dr. Gallo, who is most renowned for discovering human retroviruses, co-discovering HIV as the cause of AIDS and developing the HIV blood test continued, “Nothing is needed more than a rapid diagnostic test. Molecular tests that can be done cheaply and at home, within two hours or less time – nothing could be more valuable “We need to be able to trace; we need to be able to follow people; we need to be able to educate. This is absolutely basic, and without it we can do nothing. There is singularly nothing else more important in my mind than having rapid and reliable diagnostics.”

Dr. Bréchot was joined at the press event by presenters from the annual meeting including:

  • Linfa Wang, Duke-NUS Medical School, Singapore
  • Konstantin Chumakov, FDA Office of Vaccines Research and Review, USA
  • Ab Osterhaus, TiHo Hannover, Germany
  • Johan Neyts, Rega Institute, Belgium
  • Raymond Schinazi, Emory University, USA

Next, David Scheer, an advisor and entrepreneur in life sciences with a lifelong career in global public health non-profits, moderated a discussion titled, “From HIV to SARS-CoV-2 and Beyond.” Panelists were Dr. Gallo, Dr. Bréchot and Dr. Eric Rubin, New England Journal of Medicine Editor.  The frank COVID-19 discussion included historical perspectives, the emergence of variant strains of SARS-CoV-2, vaccine development and innate immunity, the use of existing and new drug therapies, pandemic preparedness as it relates to industry, government and academia, and that SARS-CoV-2 is naturally occurring and not manmade.

The meeting program can be found here.

About the Global Virus Network (GVN)

The Global Virus Network (GVN) is essential and critical in the preparedness, defense and first research response to emerging, exiting and unidentified viruses that pose a clear and present threat to public health, working in close coordination with established national and international institutions. It is a coalition comprised of eminent human and animal virologists from 57 Centers of Excellence and 10 Affiliates in 33 countries worldwide, working collaboratively to train the next generation, advance knowledge about how to identify and diagnose pandemic viruses, mitigate and control how such viruses spread and make us sick, as well as develop drugs, vaccines and treatments to combat them. No single institution in the world has expertise in all viral areas other than the GVN, which brings together the finest medical virologists to leverage their individual expertise and coalesce global teams of specialists on the scientific challenges, issues and problems posed by pandemic viruses. The GVN is a non-profit 501(c)(3) organization. For more information, please visit www.gvn.org. Follow us on Twitter @GlobalVirusNews.

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GVN International Press Conference September 24, 2020

GVN 2020 Special Annual Meeting Executive Summary

Global Virus Network (GVN) Presents Doherty Institute Director, University of Melbourne Professor Sharon Lewin with the Robert C. Gallo Award for Scientific Excellence and Leadership in Medical Virology

Baltimore, Maryland, USA, September 22, 2020: The Global Virus Network (GVN), comprising foremost experts around the world in every class of virus-causing disease in humans and some animals, today presented Doherty Institute Director, University of Melbourne Professor Sharon Lewin with the Robert C. Gallo Award for Scientific Excellence and Leadership in Medical Virology  Presented today at the GVN Special Annual Meeting, Professor Lewin was selected for her outstanding clinical virology research and clinical trials, her leadership in Australian medical science as Director of the Doherty Institute, and her leadership in the GVN.

Professor Lewin has an international reputation in the field of HIV latency and eradication and immune reconstitution and HIV-hepatitis B virus co-infection.

In 2020 she has worked tirelessly at the helm of the Doherty Institute which has been at the forefront of Australia’s response to the COVID-19 pandemic.

Professor Lewin said it was an incredible honour to be presented with the Robert Gallo Award.

“The GVN is among other things, dedicated to identifying, research, combatting and preventing current and emerging pandemic viruses, it’s reason for being has never been so relevant. It’s a privilege to receive the Robert Gallo Award, and to be so closely linked as a GVN Center of Excellence Director,” Professor Lewin said.

The Doherty Institute is one of 57 GVN global Centers of Excellence, which Professor Lewin co-leads with Professor Damian Purcell and Professor Peter Revill.

The award is named after GVN Co-Founder and International Scientific Advisor, Professor Robert Gallo, who is most widely known for his co-discovery of HIV as the cause of AIDS and the development of the HIV blood test.

“Sharon Lewin is an international leader in clinical research,” said Professor Robert C. Gallo, co-founder of GVN and the current Director of the Institute of Human Virology at the University of Maryland School of Medicine.  “Additionally, she has been, and will continue to be, a medical science thought leader for the field of clinical virology and a powerful presence in Australia and globally as a scientific leader of the Doherty Institute, quickly establishing this GVN Center as one of excellence. I know all in the GVN are very happy and proud to honor her.”

“I congratulate Sharon Lewin for such a well-deserved award,” said GVN President Professor Christian Bréchot.  “Indeed, this recognizes her major scientific achievements and her full commitment to both the fight against HIV and support for the Global Virus Network.”

About the Global Virus Network (GVN)
The GVN is essential and critical in the preparedness, defense and first research response to emerging, exiting and unidentified viruses that pose a clear and present threat to public health, working in close coordination with established national and international institutions. It is a coalition comprised of eminent human and animal virologists from 57 Centers of Excellence and 10 Affiliates in 33 countries worldwide, working collaboratively to train the next generation, advance knowledge about how to identify and diagnose pandemic viruses, mitigate and control how such viruses spread and make us sick, as well as develop drugs, vaccines and treatments to combat them. No single institution in the world has expertise in all viral areas other than the GVN, which brings together the finest medical virologists to leverage their individual expertise and coalesce global teams of specialists on the scientific challenges, issues and problems posed by pandemic viruses. The GVN is a non-profit 501(c)(3) organization. For more information, please visit www.gvn.org and follow on Twitter @GlobalVirusNews.

Current Status of COVID-19 Vaccine Development

As the COVID-19 pandemic expands, interests in the progress of vaccine development are intensifying. Despite an unprecedented rate of progress, it is still uncertain when a safe, effective vaccine will be available for wide distribution to the public. Successful vaccine development goes through a series of stages, from animal studies for the evaluation of its protective immunogenicity to phase 1 (safety and antibody production), phase 2 (safety and immunogenicity by including a placebo group), and phase 3 (verification of safety, and efficacy in, a large population group) clinical trials. This is obviously a long, drawn out process, yet it is necessary to ensure the efficacy and safety of vaccines. In addition, it takes very high numbers of participants to generate meaningful and significant statistics to prove vaccine protection. This makes these trials expensive and their enrollment process lengthy, but phase 3 trials are clearly necessary, and are the most important step for its approval.

Immunogenicity studies are especially critical because there is not yet a clear understanding of what constitutes a protective immune response. Neutralizing or IgG antibody titers against the spike (S) protein do not seem to correlate inversely with disease severity, although it may be that rapid expression of such antibodies would be protective. Another issue is that neutralizing antibodies may only last a few months. However, immune memory cells may facilitate rapid production of such antibodies after infection. Even less is known about the role or relevance of T cell responses in protection. With all these caveats in mind, we will discuss nine candidate vaccines that are in the most advanced stages of development.  Most, but not all, are focused exclusively on the S protein, in large part because it is the target of neutralizing antibodies.

There are currently two vaccines in the late stage of development that depend upon injection of mRNA encoding the spike protein or portions including the receptor binding domain (RBD) of the S protein. These have an advantage of being easy to produce but have the disadvantage of needing to be stored at 4°C, requiring a cold chain supply, thus presenting difficulties for use in low-income countries. These two vaccines are produced by Moderna and Pfizer/BioNTech. Its limitations associated with the intracellular instability and inefficient delivery of mRNA have been addressed by chemically modifying the RNA and encapsulating it in lipid nanoparticles.

The Moderna vaccine (mRNA-1273) and one of the two Pfizer vaccines (BNT162b2) encode prefusion conformation of the S proteins. The other Pfizer vaccine (BNT162b1) encodes trimerized soluble S protein receptor binding domains on a peptide linker scaffold. The Moderna vaccine was protective in rhesus macaques. Human phase 1 trial results were reported in June by demonstrating its safety and immunogenicity with induction of binding and neutralizing antibodies equivalent to the levels that are seen in natural infection. The antibody levels persisted until at least day 43 post-vaccination. A phase 2 trial with 600 participants was begun in June. Phase 3 trials to determine efficacy and safety were initiated in August and will have 30,000 participants.

Pfizer decided to concentrate on BNT162b2, as it is equally immunogenic to BNT162b1 but generates fewer side effects. There do not appear to be any reports of trials with non-human primates. Three phase 1 trials showed that both vaccines elicited binding and neutralizing antibodies, but lesser side effects led to the selection of BNT162b2 for phase 3 trials (Publication 1, Publication 2). Trials began in August and, as with the Moderna trials, aim to enroll 30,000 participants.

The other nucleic acid-based vaccine, developed by Inovio (INO-4800), is comprised of DNA encoding the S protein. The DNA vaccine, unlike the mRNA vaccines, is stable at room temperature. The DNA is injected intramuscularly and then electroporated into cells by a hand-held device delivering a brief electric pulse.  The vaccine was partially protective in rhesus monkeys against a viral challenge three months after vaccination as judged by a reduction in viral titers. Inovio claims that antibody and/or T cell responses were induced after two doses of the vaccine in 94% of the 40 participants in Phase 1 trials, but they have not yet published the results. They are scheduling Phase 3 trials for September.

The Novavax vaccine candidate, NVX-CoV2373, is a full-length stabilized spike protein produced in insect cells and formulated into a lipid nanoparticle. Reports from a phase 1-2 trial showed that binding and neutralizing antibodies were elicited(1). Antibody levels were greatly increased, and T cell activities (especially Th1) were induced when NVX-CoV2373 was combined with a saponin-based adjuvant. Phase 3 trials are planned for late 2020.

There are currently three late stage vaccines that use adenoviral vectors to deliver their payloads to express the S protein. These include AstraZeneca/University of Oxford, which uses a chimpanzee adenovirus originally isolated from a chimp stool sample, Johnson and Johnson/Janssen (adeno26) and Cansino/Beijing Institute of Biotechnology (adeno5), the two latter of which are human adenoviruses. All three adenoviral vectors have been genetically modified to render them incapable of self-replication. The reasoning behind the use of a chimp adenovirus was to avoid the possibility that vaccinees previously infected by human adenoviruses would mount in an immune response against the vector, thus diminishing the efficacy of the vaccine.

The AstraZeneca vaccine, ChAdOx1 nCoV-19, was shown to partially protect rhesus macaques from viral challenge(2). Out of 6 vaccinated animals, none showed signs of pneumonia or lung pathology, while 3 of 6 controls developed interstitial pneumonia. The vaccine elicited binding and neutralizing antibodies against the S protein as well as Th1 and Th2 responses. Protection was not, however, sterilizing. Vaccinated animals had reduced viral loads in their lower respiratory tracts compared to controls, but viral loads in the nasopharynx were equivalent in both groups. A randomized phase1/2 trial with >1,000 subjects was injected with either ChAdOx1 nCoV-19 or the same vector with an unrelated antigen(3). The vaccine elicited binding and neutralizing anti-S antibodies as well as a T cell response without exhibiting serious adverse events. ChAdOx1 nCoV-19, currently in phase 3 trials, has recently been in the news because of a potential serious adverse reaction that temporarily halted the trials. A vaccinated women developed a severe spinal inflammation (transverse myelitis), which can occasionally develop following viral infections. She has since recovered, and it is not clear whether this is related to the vaccine. Trials have since resumed in Britain, but the Food and Drug Administration (FDA) has not yet approved resumption in the US. There are two ways to view this event. It could be considered to reflect the speed with which these vaccines are being developed and might be a cause for apprehension.

The Johnson and Johnson vaccine, Ad26.COV2.S, expresses a prefusion conformation of S protein (proline-stabilized S protein) in a human adeno 26 vector. In rhesus macaques, vaccinated animals developed high levels of binding and neutralizing anti-S protein antibodies and a Th1 biased T cell response(4). The authors suggested that neutralizing antibodies, but not cell-mediated immune activities, were correlative on protection. All 20 controls were infected and developed minimal disease after intratracheal and intranasal challenge. Five of six vaccinated animals were protected from detectable infection, and the sixth had a 3-4 log reduction in virus loads. Ad26.COV2.S is currently in phase 1/2 trials with 11,000 subjects that was started in June. Phase three trials are scheduled for September with 30,000 participants.

The CanSino vaccine, Ad5-S-nb2, contains a codon-optimized gene expressing the S protein. In rhesus macaques, a single dose elicited neutralizing and S protein binding antibodies and activated cell mediated immune responses after intramuscular inoculation(5). Intranasal inoculation induced antibody production but only weak cellular immunity. In an open label non-randomized trial, the vaccine was immunogenic in humans and generally well tolerated with the main adverse effect of being pain(6).  A phase 2 trial with ~600 participants confirmed immunogenicity and safety(7).

There are three vaccines, developed by Sinovac, Beijing Institute of Biological Products, and Sinopharm, that are based upon chemically inactivated whole SARS-CoV-2. These vaccines, unlike the others, contain all the viral structural proteins, and thus, might be expected to induce a wider T cell response than the other vaccines, which contain only the S protein. The Sinovac candidate, Coronavac, elicited neutralizing and binding antibodies against the S protein(8). The highest vaccine dose protected animals completely against an intratracheal challenge, and lower doses prevented severe interstitial pneumonia and resulted in greatly reduced vial loads. In a phase 1/2 trial, Sinovac claimed that 90% of the volunteers developed neutralizing antibodies and had no serious adverse effects. There was no sign of antibody-dependent enhancement within the time frame reported. Sinovac initiated phase 3 trials in Indonesia and Brazil in August and is planning another trial in Bangladesh. Another inactivated virus vaccine (BBIBP-CorV), developed by the Beijing Institute of Biological Products, induced anti-S protein binding and neutralizing antibodies in rhesus macaques and cynomolgus monkeys and protected rhesus macaques from intratracheal challenge(9). BBIBP-CorV will soon be entering human trials. Two other similarly inactivated whole vaccines, produced by Sinopharm, induced neutralizing antibodies in phase 1 trials and had no serious adverse effects(10). Phase 3 trials with this vaccine were started in July in the UAE. 

The speed of vaccine development with which this has happened is remarkable. The general take home message gleaned from an overview of these vaccines is that they induce neutralizing antibodies, stimulate T cell-mediated activity, and partially or completely protect non-human primates from infection and/or serious disease. None appear to cause an undue level of adverse events. The most pressing question is of course when one or more will be available. However, many uncertainties remain given the lack of robust clinical data. We still need to wait for finalization of phase III trials to confirm the safety and efficacy of the vaccine candidates. In particular, potential induction of antibody-dependent enhancement could be a concern. Immunogenicity of vaccine candidates are focused on the induction of neutralizing antibodies. Furthermore, they are mostly administrated by using the intramuscular route, thus limiting the induction of mucosal immunity. Intranasal immunization approach also needs to be considered. In addition, most vaccine candidates might require two doses (prime and boost vaccinations) to enhance their protective efficacy. For a global vaccination, this poses challenges financially and logistically. Therefore, we also need to consider the non-specific protective effects of live vaccines based on stimulation of innate immunity and trained innate immunity (i.e. epigenetic changes induced by live vaccines).

References

 

  1. C. Keech et al., Phase 1-2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine. N Engl J Med, (2020).
  2. N. van Doremalen et al., ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in rhesus macaques. Nature, (2020).
  3. P. M. Folegatti et al., Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial. Lancet 396, 467-478 (2020).
  4. N. B. Mercado et al., Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques. Nature, (2020).
  5. L. Feng et al., An adenovirus-vectored COVID-19 vaccine confers protection from SARS-COV-2 challenge in rhesus macaques. Nat Commun 11, 4207 (2020).
  6. F. C. Zhu et al., Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial. Lancet 395, 1845-1854 (2020).
  7. F. C. Zhu et al., Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet 396, 479-488 (2020).
  8. Q. Gao et al., Development of an inactivated vaccine candidate for SARS-CoV-2. Science 369, 77-81 (2020).
  9. H. Wang et al., Development of an Inactivated Vaccine Candidate, BBIBP-CorV, with Potent Protection against SARS-CoV-2. Cell 182, 713-721 e719 (2020).
  10. S. Xia et al., Effect of an Inactivated Vaccine Against SARS-CoV-2 on Safety and Immunogenicity Outcomes: Interim Analysis of 2 Randomized Clinical Trials. JAMA, (2020).

 

Global Virus Network Announces 2020 Special Annual Meeting

World-Renowned Scientists Come Together to Address COVID-19, Ramifications for Future Epidemics and Pandemics  at September 22-23 Virtual Meeting

Editors’ note: Media are invited to participate in a virtual press conference on Thursday, September 24 at 9 am ET, which will highlight key outcomes/findings of the meeting. GVN founders and session chairs will present the findings, followed by a QA session for news media. To register or learn more, email [email protected]

Baltimore, Maryland, USA, September 17, 2020: The Global Virus Network (GVN), a coalition of the world’s leading medical virology research centers working to prevent illness and death from viral disease, will hold its 2020 GVN Special Annual Meeting virtually September 22-23, 2020.  The current SARS-CoV-2 (COVID-19) crisis has now been ongoing for more than seven months and it is timely to investigate what went wrong, what went right, and what GVN proposes for future pandemics.  GVN, a partner of international institutions such as the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC), looks forward to providing guidance on lessons learned from this current crisis and future preparedness, particularly as we prepare for a potential second wave of SARS-CoV-2 infections.

Discussion topics will include vaccine development, therapeutics and diagnostics, as well as ensuring that scientific truth and fact prevails. This analysis will examine key pandemic response strategies, including a universal masking policy, creating a consortium to improve diagnostics and vaccines, enhancing peer reviewed processes and establishing reliable channels for information sharing. The invitation-only meeting will bring together experts in virology, epidemiology and public health, including representatives of GVN Centers of Excellence, to facilitate international collaboration and information sharing.

“There could not be a more critical time for our organization to host a special meeting as the world continues to battle the COVID-19 pandemic. We look forward to the collaborative ideas, insights, perspectives and recommendations that our Annual Meetings consistently provide, enlightening our members and the broader global scientific community and world leaders in their work addressing virus-causing diseases,” said GVN President Christian Bréchot, MD, PhD. “And at this critical time, we need shared expertise and strategies as we work together to anticipate the second wave of COVID-19 and future pandemics.”

“If there existed a collaborative, first research response such as the GVN when I was working on AIDS, we would have distributed the fast-moving scientific developments more rapidly and saved countless more lives.  COVID-19 is no different, the world should have been better prepared, and still it is not,” said Dr. Robert C. Gallo, co-founder of GVN and the current Director of the Institute of Human Virology at the University of Maryland School of Medicine. “The GVN Special Annual Meeting will give us the opportunity to determine what we must do to address the impending second wave of COVID-19 and be better prepared for the future epidemics and pandemics to come.”

The conference will include presentations by leading international scientists from nine countries representing 15 GVN Centers of Excellence. In addition to Drs. Gallo and Bréchot, presenters include:

 

  • Sharon Lewin of Doherty Institute, Australia
  • Edward Holmes of University of Sydney, Australia
  • Joaquim Segales of Irta-Cresa, Spain
  • Wim H. M. Van Der Poel of Wageningen University, Netherlands
  • Ben Cowling of the University of Hong Kong, China
  • Raymond Schinazi of Emory University Center, USA
  • David Block of Glinknik, USA
  • John Mellors of the University of Pittsburgh, USA
  • Rabindra M. Tirovanziam of Emory University, USA
  • Franco Buonaguro of the National Cancer Institute, Italy
  • Miguel Luengo-Oroz of Un Global Pulse, USA
  • Linfa Wang of the Duke-NUS Medical School, Singapore
  • Florian Krammer of Mount Sinai, USA
  • Amy Chung of University of Melbourne, Australia
  • Sophie Valkenburg of the University of Hong Kong, China
  • Konstantin Chumakov of the FDA Office of Vaccines Research and Review, USA
  • Marion Gruber of the FDA Office of Vaccines Research and Review, USA
  • Chirstine Stabel Benn of the University of Southern Denmark, Denmark
  • Mihai Netea of Radboud University, Netherlands
  • Gavin Cloherty of Abbott Laboratories, USA
  • David Scheer of Scheer & Company, USA
  • Mark Parrington of Sanofi, USA
  • Ab Osterhaus of TiHo Hannover, Germany
  • Matthew Frieman of the University of Maryland School of Medicine, USA
  • Gene Morse of the University of Buffalo, USA

About the Global Virus Network (GVN)

The Global Virus Network (GVN) is essential and critical in the preparedness, defense and first research response to emerging, exiting and unidentified viruses that pose a clear and present threat to public health, working in close coordination with established national and international institutions. It is a coalition comprised of eminent human and animal virologists from 57 Centers of Excellence and 10 Affiliates in 33 countries worldwide, working collaboratively to train the next generation, advance knowledge about how to identify and diagnose pandemic viruses, mitigate and control how such viruses spread and make us sick, as well as develop drugs, vaccines and treatments to combat them. No single institution in the world has expertise in all viral areas other than the GVN, which brings together the finest medical virologists to leverage their individual expertise and coalesce global teams of specialists on the scientific challenges, issues and problems posed by pandemic viruses. The GVN is a non-profit 501(c)(3) organization. For more information, please visit www.gvn.org. Follow us on Twitter @GlobalVirusNews.

Media Contacts:

Sard Verbinnen & Co
Kelly Kimberly/Kelly Langmesser
[email protected]
+1.212.687.8080

GVN
Nora Samaranayake
410-706-1966
[email protected]

 

 

Abbott partners with the Global Virus Network on a new coalition to prepare for future pandemics

In late 2019, a group of infectious disease experts had an idea— to create a coalition among leaders in the public and private sectors that could help prepare for how the global health community responds to emerging pandemics and collaborate to end major viral pandemics.

As the initial program formed between Abbott and Global Virus Network (GVN) – a global coalition of medical virologists – the group quickly realized they would be developing a blueprint for pandemic preparedness, while in the middle of one.

“We are seeing first-hand the urgent need for collaboration when it comes to a novel virus that becomes a pandemic,” says Christian Bréchot, M.D., Ph.D., and president of the Global Virus Network (GVN). “By having this coalition in place, we are essentially creating the instructional manual for how we respond to emerging pandemics, while also creating the vehicle to do so.”

A global virus coalition

The GVN Corporate Centers of Excellence Coalition was first created in late 2019 as a way to bring together the world’s foremost virologists and prominent companies to catalyze and facilitate the development, evaluation and testing of diagnositcs, therapeutics, treatments and vaccines for viral epidemics and pandemics that pose a threat to public health.

As a leader in infectious disease testing and blood screening, Abbott joined as the inaugural member of the coalition.

“We know that every day matters when it comes to responding to a pandemic, which is why collaboration and preparedness are critical,” said Gavin Cloherty, Ph.D., head of Infectious Disease Research, Diagnostics, Abbott. “With this partnership, we are creating a SWAT team of highly trained scientists to share knowledge, techniques and innovative tests and technologies to better understand both existing and emerging viruses.”

The collaboration with GVN plans to focus on three initial areas:

  • Strengthening preparedness
  • Sharing research on known pathogens and emerging pathogens
  • Providing insights on the potential impact of this research

Collaboration during the COVID-19 pandemic

In the early weeks of the pandemic, Abbott brought together a team of its scientists to develop diagnostic and antibody tests to detect the virus and the antibodies that develop after an infection.

One of the key elements for developing these tests were virus samples to ensure the accuracy of our test. Through the Corporate Centers of Excellence program, Abbott collaborated with GVN to identify additional virus samples in different patient populations and has worked with GVN to determine new locations to conduct research.

The coalition is also developing the framework to collaborate and share research on the COVID-19 (SARS-CoV-2 ) virus. Abbott and GVN are establishing a SARS-CoV-2 biobank – or repository that stores biology samples – to study and validate antibody tests.

Planning for the future

From Smallpox, to HIV or the latest efforts for COVID-19, history has shown the impact infectious diseases can have and the need to stay ahead of emerging viruses.

The Centers of Excellence will take learnings developed for the fight against COVID-19 to prepare for future pandemics.

“In the early days of the pandemic, data-sharing was critical to helping the research community understand the virus. We can take the infrastructure from our SARS-CoV-2 biobank in development and use it as a template for future emerging viruses,” said Cloherty.

By developing an integrated global network of scientists and industry leaders, the healthcare community can work together to help in the fight against our current pandemic and quickly respond to future infectious disease outbreaks.

 

About the Global Virus Network (GVN)

The Global Virus Network (GVN) is essential and critical in the preparedness, defense and first research response to emerging, exiting and unidentified viruses that pose a clear and present threat to public health, working in close coordination with established national and international institutions. It is a coalition comprised of eminent human and animal virologists from 55 Centers of Excellence and 10 Affiliates in 33 countries worldwide, working collaboratively to train the next generation, advance knowledge about how to identify and diagnose pandemic viruses, mitigate and control how such viruses spread and make us sick, as well as develop drugs, vaccines and treatments to combat them. No single institution in the world has expertise in all viral areas other than the GVN, which brings together the finest medical virologists to leverage their individual expertise and coalesce global teams of specialists on the scientific challenges, issues and problems posed by pandemic viruses. The GVN is a non-profit 501(c)(3) organization. For more information, please visit www.gvn.org. Follow us on Twitter @GlobalVirusNews

 

GVN MEDIA CONTACT
Nora Samaranayake
Phone:  410-706-1966
Email:    [email protected]

 

COVID-19 Vs. Influenza: Influenza Vaccination Amid COVID-19 Pandemic

Severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2), a highly contagious virus, emerged in 2019 from Wuhan, China (1). It rapidly spread around the world causing a novel acute respiratory disease, coronavirus disease 2019 (COVID-19). The World Health Organization (WHO) declared COVID-19 a pandemic on March 11, 2020. Consequently, the current COVID-19 pandemic impacts global health and economies to unprecedented levels. As of August 17, 2020, over 21,760,000 cases have been confirmed in more than 188 countries, with over 776,580 deaths, and growing daily. The spectrum of disease with SARS-CoV-2 ranges from asymptomatic infection to severe, often fatal disease. Patients with mild disease (80%) have fever, cough, sore throat, loss of smell, headache, and body aches (2). A surge of COVID-19 patients resulted in enormous challenges for capacity and patient flow in hospitals and health care systems globally. Currently, we have limited interventional strategies in curbing COVID-19, and attention has been focused on the progress in the development of vaccines and therapeutics since the beginning of pandemic. Despite the progress, one cannot exclude that the virus would be continuously circulating as a seasonal virus even after the availability of a vaccination program.

Seasonal influenza is a major cause of morbidity, mortality, resulting in a burden on  healthcare services globally every year. According to the WHO, up to 650,000 deaths are associated with seasonal influenza respiratory infections annually. In the Northern Hemisphere, the 2020-2021 influenza season will coincide with the continued circulation of SARS-CoV-2. The nature of disease similarity between COVID-19 and influenza is cause for great concern. In addition, SARS-CoV-2 and influenza viruses have similar transmission characteristics. The two viruses are spread by contact and airborne transmission. The incubation period for influenza is short, typically 1–2 days, whereas for SARS-CoV-2, it is 4.5–5.8 days (2). The basic reproductive rate (R0, the average number of secondary transmissions from one infected person) for SARS-CoV-2 is estimated to be 2·5 (range 1·8–3·6) compared with 2·0–3·0 for the 1918 influenza pandemic, 1·5 for the 2009 influenza pandemic, and 1.3 for seasonal influenza viruses (3, 4). COVID-19 mortality risk has been highly concentrated at old ages (> 65 years old) and those, in particular, males, with underlying medical conditions (called co-morbidities), including hypertension, diabetes, cardiovascular disease, and immunocompromised states (2). Furthermore, SARS-CoV-2 can also infect younger individuals. In particular, children have shown to be susceptible to infection (5). Although most of the infections run a rather benign course, some children may develop severe primary and unique secondary inflammatory complications of infection, including multisystem inflammatory syndrome of children (6). Indeed, while children comprise 22% of the U.S. population, recent data show that 7.3% of all cases of COVID-19 in the U.S. reported to the Centers for Disease Control and Prevention (CDC) were among children (as of August 3rd, 2020). The number and rate of cases in children in the U.S. have been steadily increasing from March to July 2020, even though the incidence of SARS-CoV-2 infection in children is known to be underrated due to a lack of widespread testing. Opening schools in many locations might change a dynamic of transmission of SARS-CoV-2 and COVID-19 cases among children. Similar to COVID-19, influenza-associated excess mortality in elderly individuals related to a range of other chronic health conditions, including cardiovascular causes, diabetes, neoplasms and renal disease (2). In contrast to COVID-19, children are believed to have the highest rates of infection and complications arising from influenza, thus leading to high rates of excess outpatient visits, hospital admissions and antibiotic prescriptions (7). Infections among children can also drive influenza epidemics due to their increased susceptibility to infection and greater contribution to the spread of virus in the community.

Vaccination can be the most efficient and effective measures in controlling the current COVID-19 pandemics. Researchers are developing more than 170 vaccines against the coronavirus, and 47 vaccines are in human trials. In contrast, annual influenza vaccination is available with inactivated influenza vaccines, recombinant influenza vaccine, and live attenuated influenza vaccine. This the main public health intervention in reducing the burden of disease (8). The WHO has recognized some priority target groups for annual influenza vaccination, including pregnant women, children aged 6 months to 5 years, the elderly, subjects with specific chronic conditions, healthcare workers, and international travelers (9). However, influenza vaccination rates among children aged 6 months to 17 years remain low compared with other routinely recommended childhood vaccines. In-plan vaccination coverage during the 2016–17 season was 67.7% in infants (born 2015), 49.5% in toddlers (born 2012–2014), 35.0% in school-aged children (born 2004–2011), and 22.3% in teenagers (born 1999–2003) (10). Like vaccination coverage, vaccination opportunities decreased with age. Along with continued efforts to reduce missed opportunities, effective strategies to bring children to their doctor for annual influenza vaccination are needed, particularly for older children. Among adults, influenza vaccination coverage (≥18 years) was 45.3% in the U.S. during 2018–19 influenza season (11).

The information regarding COVID‐19 and influenza coinfection is limited. Unless screening patients with COVID‐19, the coinfection remains undiagnosed and underestimated. The severity of disease resulting from the co-infections varies by causing a more severe course with a fatal outcome or mild illness (12). Although this needs to be further evaluated, influenza immunization for high-risk groups can reduce the possibility of influenza infection and co-infection with SARS-CoV-2 and complications associated with diagnostics and antiviral treatment. A COVID-19 infection prediction model has also shown that influenza vaccines could reduce COVID-19 infection risk (13). This will also alleviate burden on the health care system by avoiding an overload of health services and hospitals associated with influenza infections (i.e., outpatient illnesses, hospitalizations, and intensive care unit admissions). Influenza vaccine is safe for elderly and children with a proven record over the past 50 years (7). Therefore, influenza vaccination can be a critical component of response to the COVID-19 pandemic. However, there has been a prediction that the COVID-19 pandemic could decrease influenza vaccination, since the pandemic resulted in a 38 percent drop in consumer spending on health care and loss of health insurance (14). In response, CDC already arranged for an additional 9.3 million doses of low-cost flu vaccine for uninsured adults, up from 500,000. The agency expanded plans to reach out to minority communities. It is uncertain how this upcoming influenza season will evolve under the current circumstance. In general, taking an influenza vaccine can be a good preventive strategy for public health.

 

Readers’ Comments are Welcome

 

References

  1. 2020. Rolling updates on coronavirus disease (COVID-19). July 31, 2020. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/events-as-they-happen.
  2. Subbarao K, Mahanty S. Respiratory Virus Infections: Understanding COVID-19. Immunity. 2020;52(6):905-909. doi:10.1016/j.immuni.2020.05.004.
  3. Petersen E, Koopmans M, Go U, Hamer DH, Petrosillo N, Castelli F, Storgaard M, Al Khalili S, Simonsen L. Comparing SARS-CoV-2 with SARS-CoV and influenza pandemics. Lancet Infect Dis. 2020 Jul 3;20(9):e238–44. doi: 10.1016/S1473-3099(20)30484-9.
  4. Biggerstaff, M., Cauchemez, S., Reed, C. et al. Estimates of the reproduction number for seasonal, pandemic, and zoonotic influenza: a systematic review of the literature. BMC Infect Dis 14, 480 (2014). https://doi.org/10.1186/1471-2334-14-480
  5. Han MS, Choi  EH, Chang  SH,  et al.  Clinical characteristics and viral RNA detection in children with coronavirus disease 2019 in the Republic of Korea.   JAMA Pediatr. Published online August 21, 2020. doi:10.1001/jamapediatrics.2020.3988.
  6. Feldstein LR, Rose  EB, Horwitz  SM,  et al; Overcoming COVID-19 Investigators and the CDC COVID-19 Response Team.  Multisystem inflammatory syndrome in U.S. children and adolescents. N Engl J Med. 2020;383(4):334-346. doi:10.1056/NEJMoa2021680.
  7. Sullivan SG, Price OH, Regan AK. Burden, effectiveness and safety of influenza vaccines in elderly, paediatric and pregnant populations. Ther Adv Vaccines Immunother. 2019 Feb 7;7:2515135519826481. doi: 10.1177/2515135519826481. PMID: 30793097; PMCID: PMC6376509.
  8. Grohskopf LA, Alyanak E, Broder KR, et al. Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices – United States, 2020-21 Influenza Season. MMWR Recomm Rep. 2020;69(8):1-24. Published 2020 Aug 21. doi:10.15585/mmwr.rr6908a1.
  9. World Health Organization (WHO). Vaccines against influenza WHO position paper – November 2012. Wkly. Epidemiol. Rec. 2012, 87, 461–476.
  10. Fangjun Zhou, Megan C. Lindley, Variability in influenza vaccination opportunities and coverage among privately insured children, Vaccine, 2020, ISSN 0264-410X, https://doi.org/10.1016/j.vaccine.2020.07.061.
  11. 2019. Flu vaccination coverage, United States, 2018–19 influenza season. https://www.cdc.gov/flu/fluvaxview/coverage-1819estimates.htm#:~:text=Flu%20vaccination%20coverage%20among%20adults,than%20the%202016%E2%80%9317%20season.
  12. Co-infection with COVID-19 and influenza A virus in two died patients with acute respiratory syndrome, Bojnurd S.A. Hashemi, S. Safamanesh, M. Ghafouri, M.R. Taghavi, M.S. Mohajer Zadeh Heydari, H. Namdar Ahmadabad et al. Iran. J Med Virol (2020), 10.1002/jmv.26014
  13. Jehi L, Ji X, Milinovich A, Erzurum S, Rubin B, Gordon S, Young J, Kattan MW. Individualizing risk prediction for positive COVID-19 testing: results from 11,672 patients. Chest. 2020 Jun 10:S0012-3692(20)31654-8. doi: 10.1016/j.chest.2020.05.580.
  14. Health System Tracker. 2020. How have healthcare utilization and spending changed so far during the coronavirus pandemic? https://www.healthsystemtracker.org/chart-collection/how-have-healthcare-utilization-and-spending-changed-so-far-during-the-coronavirus-pandemic/#item-start

Prominent Australian and Russian Research Institutions Join Global Virus Network to Combat Viral Diseases

Center for Emerging Viruses, Inflammation and Therapeutics of the Menzies Health Institute Queensland (MHIQ) at Griffith University, Australia and the Chumakov Federal Scientific Center for Research and Development of Immune and Biological Products of the Russian Academy of Sciences Join GVN at Critical Time for Information Sharing

Baltimore, Maryland, USA, September 8, 2020: The Global Virus Network (GVN), comprising foremost experts around the world in every class of virus-causing disease in humans and some animals, , today announced the addition of the Center for Emerging Viruses, Inflammation and Therapeutics (EVIT) of the Menzies Health Institute Queensland at Griffith University, Australia and the Chumakov Federal Scientific Center for Research and Development of Immune and Biological Products of the Russian Academy of Sciences as its newest Centers of Excellence. The two new institutions bring GVN’s total number of Centers of Excellence to 57, along with 10 affiliates in 33 countries.

“We are pleased to have these premier institutions join us from Australia and Russia at this critical time in the global pandemic,” said Christian Bréchot, MD, PhD, who is President of the GVN and Professor at the University of South Florida.  “EVIT will strengthen our depth and collaborative network in arbovirology, particularly in the Asia-Pacific region, Southeast Asia, India, South America and South Africa. The Chumakov Center has unique expertise in varying areas of virology with many global connections, making it Russia’s leading research organization in the field of virology.”

EVIT, as part of the Menzies Health Institute Queensland, provides a critical mass of scientists and clinicians with distinct areas of expertise in emerging arbovirus diseases. The Center has excellent knowledge of viral pathogenesis and related inflammatory diseases and strong capabilities in developing treatments for emerging viruses such as chikungunya (CHIKV), Ross River (RRV), dengue, Zika (ZIKV), Japanese encephalitis (JEV) and West Nile (WNV) viruses.  Additionally, EVIT focuses on emerging viruses such as Hendra and SARS-CoV-2, and established viruses such as influenza virus and respiratory syncytial virus. The Center has a strong emphasis on both basic and translational research, which has led to several major breakthroughs in understanding how viruses cause disease. The GVN Center is led by Suresh Mahalingam, PhD, FASM, FAAM, Professor and Director, Emerging Viruses, Inflammation and Therapeutics Group, Principal Research Leader and NHMRC Senior Research Fellow at EVIT.

“GVN has the ability to contribute to the activities of major players in world health such as CEPI and GAVI, which will open up additional opportunities for our research center to establish new collaborations,” said Dr. Mahalingam. “Further, through our GVN membership, we look forward to enhancing our leadership of arbovirus research and disease preparedness in the Asia-Pacific region; establishing new collaborations with fellow GVN members; facilitating advanced training of students and researchers from the Asia-Pacific region; and, enhancing technology and knowledge transfer within the GVN.”

The Chumakov Center conducts a broad range of studies of different human and animal viruses and manufactures polio, rabies and tick-borne encephalitis vaccines, supplying up to 70% of national demand in these products. Yellow fever vaccines produced at the Chumakov Center cover more than a half of UNICEF’s Eliminating Yellow Fever Epidemics (EYE) Strategy, supporting immunization in more than 50 countries.  The Chumakov Center contains the World Health Organization’s (WHO) regional reference laboratory for polio preforming epidemiological surveillance of acute flaccid paralysis and polio as a part of Global Polio Laboratory Network for Global Polio Eradication Initiative. The Center also acts as a WHO Collaborative Center for Poliomyelitis and Enterovirus Surveillance and Research. The Center is led by Aydar Ishmukhametov, MD, DSc, Director General of the Chumakov Center and a member of the Russian Academy of Sciences.

“Our expertise in research, preclinical and clinical development and manufacturing of antiviral vaccines will be useful for GVN members.,” said Dr. Ishmukhametov.  “We look forward to collaborating with the world’s leading virology experts and for participation of our younger scientists in virology training programs through the GVN.”

About the Global Virus Network (GVN)

The Global Virus Network (GVN) is essential and critical in the preparedness, defense and first research response to emerging, exiting and unidentified viruses that pose a clear and present threat to public health, working in close coordination with established national and international institutions. It is a coalition comprised of eminent human and animal virologists from 57 Centers of Excellence and 10 Affiliates in 33 countries worldwide, working collaboratively to train the next generation, advance knowledge about how to identify and diagnose pandemic viruses, mitigate and control how such viruses spread and make us sick, as well as develop drugs, vaccines and treatments to combat them. No single institution in the world has expertise in all viral areas other than the GVN, which brings together the finest medical virologists to leverage their individual expertise and coalesce global teams of specialists on the scientific challenges, issues and problems posed by pandemic viruses. The GVN is a non-profit 501(c)(3) organization. For more information, please visit www.gvn.org. Follow us on Twitter @GlobalVirusNews.

Media Contact:

Nora Samaranayake, GVN
410-706-1966
[email protected]

Will Neutralizing and Therapeutic Antibodies Play a Role in the Treatment of COVID-19?

Interest has increasingly been focused on the potential of virus-neutralizing monoclonal antibodies (mAbs) to treat COVID-19 by passive immunization. These antibodies generally target the viral spike protein to prevent infection by blocking ACE2 receptor binding to its receptor binding domain (RBD). There are several issues, however, that need to be addressed to determine when and how they might be used. First, the levels of neutralizing antibodies present in COVID-19 patients do not always correlate to the severity of the disease, and the mean time for seroconversion in SARS patients is known to be about 2 weeks after disease onset. It is possible that timing is critical; i.e., perhaps lack of such antibodies early in infection allow vigorous viral replication, and high levels of antibody production after the development of symptom can be too late to do much good. It may be that the T cell response also plays an important role in the course of infection. Second, although immune serum from recovered patients has been touted as a potential therapy with some successful cases, evidence of its effectiveness is at best contradictory (1).

Another consideration is the nature of the antibodies themselves. This is challenging because protective immunity against SARS-CoV-2 remains unknown. Specifically, the levels and types of antibodies required for the protection need to be defined. Neutralizing antibodies against SARS-CoV-2 appear to have two sets of targets. Some bind the RBD, while others bind the spike protein outside the RBD. Some antibodies bind to the spike protein but do not neutralize the virus (non-neutralizing antibodies). Yet another consideration is that some neutralizing antibodies can lead to antibody-dependent enhancement (we have covered this in an earlier GVN Perspectives) when they are at sub-optimal concentrations. It is obvious that great care must be taken in selecting mAbs for therapeutic development. It also seems intuitive that a mixture of mAbs targeting different epitopes would provide an extra measure of protection. In clinical use, successful treatment will depend critically upon the time of mAbs administration, doses, levels of concentrations, and duration of treatment.

The general approach to identify effective antibodies has been to identify infected patients with high titers of neutralizing antibodies, sort and recover their memory B cells, sequence the heavy and light chain of mRNAs from single sorted cells to characterize the antibody produced by each cell, synthesize their mRNAs with codon optimization for high levels of expression, clone them into expression vectors and express them in transfected cells, and then screen the resultant antibody library. This has become a standardized approach to generate recombinant neutralizing antibodies (2-8). In general, they fall into two categories. The primary group of antibodies, as might be expected, targets the receptor binding domain (RBD) of the spike protein, presumably blocking its binding to the ACE2 receptor. Others bind the N-terminal domain (NTB) of the spike protein. It is not clear how these NTB antibodies neutralize SARS-CoV-2. Presumably, this is by causing allosteric changes in the tertiary or quarternary structure of the spike trimer. Currently identified neutralizing antibodies against SARS-CoV-2 are closely related to germline sequences and do not show signs of hypermutation. This indicates that neutralizing antibodies have been derived with relatively few changes from germline sequences and is a favorable sign for successful vaccine development. It would likely be best for mAb therapeutic use to include antibodies targeting both the RBD and the NTD domains of the spike protein. It should be pointed out that most neutralization assays were done with Vero (monkey kidney) cells, which are not infected by the same pathway as human airway cells(9), although ACE2 binding is required for both pathways.

Importantly, administration of neutralizing mAbs have proven to be protective in several animal models of COVID-19, including rhesus macaques, hamsters, and mice expressing human ACE2(3, 6, 8, 10-12). It is important to note that the mAbs were administered prior to or shortly after challenge. Thus, the results apply to prophylactic or early therapeutic use, but not necessarily to general therapeutic use.

As with other antivirals, it will likely be critical to administer mAbs early in disease, or as a prophylactic. Many patients with serious disease already have high levels of neutralizing antibodies, but these do not appear to ameliorate disease severity, presumably because dysregulated immune responses are driving pathogenesis in these settings. It will also be important to determine what constitutes an effective dose as well as the biologic half-life of any protective effect.

We should mention some recently described “dark horses” for prophylactic passive immunization. These are engineered single chain single domain antibody-like proteins, called nanobodies, that are derived from camelid species (llamas, alpacas). Camelids make normal antibodies, but they also make antibodies comprised of a single heavy chain containing constant and hinge domains linked to a variable region capable of binding antigens. Interestingly, the variable domain alone is also capable of binding antigens. The variable domain is about 1/10th the size of normal antibodies; hence the name nanobody. Because of this, they are far more stable than normal antibodies, allowing them to be lyophilized, heated, and aerosolized. Their small size makes them able to penetrate tissue more readily than do normal antibodies. And they are easy to produce, which makes them scalable.

Nanobodies that are able to bind the SARS-CoV-2 spike protein (both within the RBD and outside the RBD) were identified from a yeast library of synthetic nanobody sequences. Their tiny size allowed them to be trimerized with gly-ser linkers, thus yielding a multivalent molecule with greatly increased potency.  They were then subjected to saturation mutagenesis and affinity maturation, yielding at least one nanobody with picomolar neutralization potency and sub-picomolar affinity. Similar nanobodies have been isolated from a llama immunized with stabilized SARS-CoV-2 spike protein(13). Potency was increased by creating a bivalent molecule with two linked nanobodies.

Because of their size and stability, nanobodies are easily produced and stable to aerosolization. This should make it feasible to package them in inhalers. Introduction to airway tissue would be direct to potential sites of infection. They might, thus, serve as an effective prophylactic, since it would be simple to self-administer them daily. If so, they could be a game changer, but as with other potential therapeutic possibilities, the proof will be in the results.

More than 70 antibody therapies are being developed for the treatment of COVID-19. There has been anticipation that monoclonal antibodies may provide short-term protection from SARS-CoV-2 and could serve as important components of the COVID-19 pandemic response until vaccines become available. Two Phase 3 clinical trials are currently underway in the US. In general, mass-produced antibodies are complex to manufacture and are expensive. Therefore, their availability in low- and middle-income countries can be very limited. It will be also important to have a breakthrough to produce cost-effective, large quantities of antibodies.

 

 

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