So Will and When Will We Have a Vaccine?

Just to cut to the chase, we just do not know; but we may hope for one year and a half to two years, maybe less. And that will be great, but we have to distinguish between getting early evidence of efficacy and getting a vaccine ready for mass vaccination. But let’s consider background material that suggests it is likely we will indeed have a vaccine.

First, it is helpful to consider different mechanisms of immunity. There are two general types of immunity, innate and adaptive. The innate system is quick and dirty and recognizes general patterns widely shared by pathogens, such as double stranded RNA or bacterial lipopolysaccharides, but not normally present. It is mediated through the activity of cytokines and involves inflammation. The other mechanism, the adaptive immune system, is slower to respond but more precise and is mediated through antibodies and cytotoxic T cells.

Second, there are several kinds of immunization. Transfusion of immune serum or of purified antibodies, called passive immunization, can protect temporarily against infection and disease. This is currently being tried in patients.  Another type of immunization may induce a general innate immune response. Administration of some vaccines appear to induce a temporary immunity against viruses other than their targets, probably through stimulation of innate immunity. In theory, they should be able to protect against a relatively broad array of targets, which might include SARS-CoV2. This is likely the basis for the activities of BCG, which is used as immunotherapy against bladder cancer, for example. Phase 3 trials are currently enrolling subjects in Australia (BRACE) and the Netherlands (BCG-CORONA). More recently, Dr. Konstantin Chumakov (Food and Drug Administration, Office of Vaccines Research and Review) and Dr. Robert Gallo (Institute of Human Virology, University of Maryland School of Medicine, Baltimore) of the Global Virus Network have suggested repurposing polio vaccine for use against SARS-CoV2 through its induction of innate immunity. Finally, targeted vaccines can stimulate both innate and adaptive immunity. Targeted vaccines are the most commonly used vaccines, as they are the most specific and can provide durable protection.

Is a targeted vaccine for SARS-CoV2 possible? Several lines of evidence suggest the answer is yes. Worry number one is whether immune responses to the virus will be protective. Sera from infected rhesus monkeys and infected people can neutralize the virus, indicating it is possible to generate an effective response given an appropriate stimulus.  A second concern is that the virus will mutate rapidly and escape the immunity induced by vaccines. However, available sequence data suggest the overall genetic variability might be low. The virus has an RNA proofreading mechanism that reduces its mutation rate. A hopeful finding is that immune sera from people infected with the SARS1 virus (which is only 79% related at the whole genome level) neutralizes the SARS2 virus, suggesting elicited immunity will be broadly reactive. Similarly, a monoclonal antibody has been reported that neutralizes both SARS-CoV1 and SARS-CoV2.

There are many antibody-based passive immunization approaches with human and animal serum and recovered antibodies in pre-clinical development. There are also currently more than 200 targeted vaccines in widely various stages of development, including at least seven phase 1 or 2 clinical trials, and there are currently at least eight different approaches to developing a vaccine. One approach is simply to inject one or more of the viral proteins. Two other approaches involve injection and cellular take-up of either RNA or DNA encoding one or more viral proteins. Two other approaches involve vaccination with a heterologous viral vector derived from adenovirus, lentivirus, measles, or influenza virus, which has been engineered to express SARS-CoV2 proteins. These viral vectors can be either replication incompetent or able to replicate to various extents. Another type of vaccine vehicle is a virus-like particle (VLP), made artificially from viral proteins but lacking a viral genome. The SARS-CoV2 protein of interest is attached to the outer surface of the VLP. The other two vaccine approaches use whole SARS-CoV2 virus, either in killed form or attenuated so that its ability to replicate is severely compromised.

Obviously, testing for safety and efficacy is critical. Animal testing provides a way to obtain preliminary safety and efficacy data from candidate vaccines relatively quickly, because animals can be challenged with live virus. Drawbacks are that they may not accurately mimic the pathogenesis in humans and their immune responses may differ from that of humans. A study from China reported that vaccination with inactivated virus protected 8 rhesus macaques from viral challenge, but the numbers are small. The vaccinated macaques also developed antibodies able to neutralize different strains of the virus. They observed no harmful effects, including enhancement, in which a vaccine induces an immune response that makes infection more severe.

The gold standard in vaccine efficacy testing is obviously controlled clinical trials in humans. There are two ways to do this. One is with a large cohort of people from a group that has a high attack rate from the virus. Obvious, the more susceptible the test population, the fewer the numbers and shorter the time period required for a definitive answer. The most straightforward way, however, is to challenge vaccinated and unvaccinated unpaid volunteers with virus. This has the advantage that far fewer numbers are needed than in trials using an unchallenged general population, and results are obtained more quickly. However, such an approach is obviously fraught with ethical concerns.

As mentioned above, there are at least seven phase 1 or 2 trials of targeted vaccines now underway, several of which hope to have a vaccine by fall. An RNA-based vaccine by Moderna (clinical trials ID NCT04283461) has been reviewed by the FDA for phase 2 testing, and it is hoped to start phase 3 trials this summer. A Chinese whole killed virus vaccine candidate by Sinopharm (Chinese Clinical Trial Registry IdentifierChiCTR2000031809) has reached phase 2 status. The Oxford Vaccine Group is conducting a phase 1/2 trial with a vaccine (clinical trials ID NCT04324606) based on a chimp adenoviral vaccine vector that reportedly has shown protection in rhesus macaques.  A vaccine developed by Pfizer and BioNTech, called BNT162, is based on modified RNA (clinical trial ID NCT04368728). A phase 1/2 trial is planned in Germany and the United States. Inovio’s vaccine, called INO4800, is a DNA-based vaccine. They are currently planning a phase 1 trial in the United States and a phase 1/2 trial in South Korea (clinical trials ID NCT04336410). CanSino Biologics has an adenovius 5-based vaccine candidate that the company announced has passed phase 1 trials and are initiating a phase 2 trial (clinical trials ID NCT04313127). Sinovac has initiated phase 1 trials with a vaccine candidate based on inactivated virus plus adjuvant (clinical trials ID NCT04352608).

With the large number of approaches, the relative genetic stability of the virus, and hopeful results from animal trials, it seems likely a vaccine will be successfully developed. The big question, of course, is how soon. The best case seems to be by fall of 2020. Pressure to speed up the schedule may spur further considerations of the ethics of human volunteer challenge studies. The development of better antiviral therapies may influence considerations of these types of trials, as it would make them somewhat safer.

 

Read the June 2, 2020 update here

View All GVN SARS-CoV-2 Perspectives

 

Testing for SARS-COV-2

Testing, Testing, Testing…

The uncertainties about SARS-CoV-2 include critical questions such as what the death rate is for infected people, and what the infection rate is for the general public. This makes testing for infection of critical importance. There are numerous ways to establish the presence of infection. One is recovery of live virus, which in case of SARS-CoV-2 requires culturing the virus in biosafety level 3 containment. Although this would seem to be a gold standard, BSL3 facilities are not widely available, so this type of test is not routinely done. Another is to test for viral proteins, known as antigen testing. This seems to be amenable to high throughput testing, but reliable diagnostic tests have not yet become available. A third is to detect and measure viral RNA, generally done by PCR amplification following reverse transcription of viral RNA. It can be performed relatively readily in high quantity, but it is only an indirect indication of live virus. Even badly fragmented RNA can register as a positive, and positive results simply indicate that virus is being shed from somewhere within a patient, or has been recently. Thus, although recovered patients and asymptomatic people can be viral RNA positive, it is unclear as to what extent they can actually transmit virus without confirming live virus by isolation in a BSL3 facility. Fourth, serologic tests for antibodies to the virus can be performed on a massive scale, but depend critically on what the false positive and false negative rates are for a given test, and these can vary considerably among different test kits. The presence of antibodies means a person has been or is infected but may not still be infected at the time of the test.  Fifth, PCR tests similar to viral RNA tests can detect spliced or subgenomic RNA. In infected cells, full length viral RNA is spliced into a variety of smaller RNAs in order to encode many of the viral proteins. Thus, the presence of spliced subgenomic RNA indicates the presence of currently infected cells somewhere within the test subject. This process is somewhat labor intensive.

  • Of than these types of tests, the two that are amenable to mass testing and currently being used are viral RNA analysis and serologic tests, which are being widely and increasingly employed. To date, by far most testing that has been reported is for viral RNA. RNA is usually quantified based upon how many cycles of polymerase chain reaction are required to generate a detectable signal. These types of tests are highly specific (defined as the rate of false positives), but may lack sensitivity (defined as the rate of false negatives. This is not because of an intrinsic lack of sensitivity, but is because detection depends on the site from which the tested sample is taken. While throat and nasal swabs give reasonable sensitivity, bronchial alveolar lavage would be more sensitive, but collection is probably too onerous to be practicable. Saliva has been suggested as being conveniently obtained, but provides somewhat less sensitivity than nasopharyngeal swabs.(1) Wolfel et al.(2) performed RNA analysis of a number of tissues from moderately sick infected individuals. Swabs, saliva and stool contained viral RNA, although no live virus could be obtained from stool samples. The swabs and saliva contained live virus. Live virus could not be obtained after 8 days, although viral RNA remained positive. Urine and serum samples were never positive for viral RNA. Thus, detection of RNA in a sample is not tantamount to detection of infectious virus in the sample, or even in the tested individual.

Serologic tests for antibodies are becoming widely available and have the potential to make widespread testing much faster. As mentioned above, the presence of antibodies can indicate either that a person is infected or has been infected, and so does not necessarily indicate the presence of live virus. Following infection, IgM is the first antibody class produced, and so is more of an indicator of recent infection than is IgG, which is produced later. IgG tends to persist longer than IgM, and more sensitive to detect than past infections. Some antibody tests detect both classes; others only one. Samples collected include drawn blood or finger pricks. Widespread use of these tests has been hampered somewhat by the large number of tests of varying quality that are available; it is currently somewhat of a Wild West situation.

The specificity and sensitivity of these tests, defined respectively as the rate of false positives and false negatives, is critical for their usefulness, depending on whether they’re used for mass screening or diagnostic purposes. For diagnostic testing, sensitivity and specificity are obviously both important. For mass testing, specificity is absolutely critical.  Let’s consider using a test that is 95% specific for a population of 100 people that is 5% infected. The test will detect the 5 infected people. In addition, ~5 uninfected people will test positive, leading to the conclusion that 10% of the population is infected, even though the true infection rate is only half that. For reference, the test made by Abbot, which will be used in mass testing, has been reported as 100% sensitive, 99.5% specific. The other test that is likely to be used in mass testing is one by Roche. As of this writing, the accuracy and sensitivity data are not available, but will presumably be similarly high. Consideration of specificity should be taken into account when evaluating reports of unexpectedly high seroprevalence such as the study from Santa Clara County. The article can be accessed here, along with a number of critiques. Mass testing in the future should lend a lot more clarity to the true situation. It would be of interest to follow up positive serologic tests with confirmatory tests for RNA.

 

  1. E. Williams, K. Bond, B. Zhang, M. Putland, D. A. Williamson, Saliva as a non-invasive specimen for detection of SARS-CoV-2. J Clin Microbiol, (2020).
  2. R. Wolfel et al., Virological assessment of hospitalized patients with COVID-2019. Nature, (2020).

View All GVN SARS-CoV-2 Perspectives

Antivirals in the Time of Coronavirus

An Evaluation of Remdesivir and Hydroxychloroquine

Many years ago, efforts to contain HIV resulted in the first widespread successful use of antiviral drugs, including deoxynucleotide analogs such as AZT, able to terminate reverse transcription of viral RNA. The current coronavirus pandemic has spurred extensive efforts to identify effective and safe anti-SARS-CoV-2 drugs. Recent reports have excited interest in Gilead’s remdesivir. Remdesivir’s activity is somewhat analogous to AZT, in that it is a nucleotide analog, but it has a 3-OH group and is not therefore a classical RNA chain terminator. Nevertheless, an analysis in vitro shows that it causes termination of transcription of viral RNA by RNA-dependent RNA polymerase RDRP 3 residues after its incorporation. There are some excellent reports characterizing in vitro activity of remdesivir against SARS-CoV-2 RDRP (1-4).

Remdesivir use has some potential issues. It is not orally bioavailable and must be infused. Treatment duration is a question still to be answered. Cost could be an issue. The SARS-CoV-2 has a 5’-3’ exonuclease which potentially could remove inappropriate nucleotide analogs, but at least in vitro with purified RDRP, this does not appear to happen.

Remdesivir (credit: Ulrich Perrey / Pool via Reuters)

The big question is of course is what is its therapeutic value? The recent excitement has come from two reports. One, in the New England Journal of Medicine, reported results from an uncontrolled compassionate use trial(5). Of 53 patients, 68% showed clinical improvement. More dramatic results were reported during a faculty video discussion at University of Chicago. Out of 113 patients with severe disease treated with remdesivir, most were successfully discharged and only two died. Again, however, this amounts to an uncontrolled trial, although the results are quite encouraging. These results represent preliminary findings from a trial sponsored by Gilead with 2,400 severe disease cases and 1600 moderate disease cases which is comparing treatments of five days duration with those of 10 days duration, so there is no true control group. However, further results are eagerly anticipated.

It appears that at the very least, targeting RDRP will be a fruitful approach. The development of an orally bioavailable version of remdesivir seems important. Since the structure of the RDRP is known, design of more powerful inhibitors should be possible. Finally, processing of the viral polyproteins into their functional forms requires a viral protease, called 3CL, for which it should be possible to design inhibitors. Protease inhibitors have proven highly effective in the cases of HIV and hepatitis C virus and could prove a useful alternative or additional target against SARS-CoV-2. Candidates for 3CL inhibitor lead compounds have already been identified(6).

Hydroxychloroquine has also received some attention, although its benefits are not yet clear, and it has some risky cardiac side effects. Although hydroxychloroquine has some activity in vitro against SAR-CoV-2 as well as other coronaviruses, it does not appear to have anti-coronaviral activity in infected animals. There have been several small studies reported in Covid19 patients. One in France, published online, showed a reduction in viral RNA in patients treated with hydroxychloroquine ± azithromycin.  However, this was not a randomized trial, had small numbers of patients, and had a number of methodological flaws. The other study, a controlled multicenter trial in China with 75 patients treated and 75 in the control arm. No effect was noted on viral RNA levels, but some clinical benefit was observed. A trial in Brazil was halted due to cardiotoxocity. The effects of hydroxychloroquine have been attributed to alteration of the endosomal compartment, affecting viral entry; alteration of glycosylation of ACE2, the spike protein receptor, reducing affinity; and immunomodulation, lowering an overly active inflammatory response. Its usefulness in Covid19 thus remains unsettled.  More recently, a larger but still non-controlled study was reported by the Veterans Administration with 368 patients (hydroxychloroquine alone, n=97; hydroxychloroquine plus azithromycin, n=113; and no hydroxychloroquine, n=158).   No benefit was observed; deaths were higher in the hydroxychloroquine group. The benefit/risk ratio of hydroxychloroquine is still unclear. Novartis is initiating a large clinical trial in the US to determine efficacy that could help answer this question.

  1. Y. Gao et al., Structure of the RNA-dependent RNA polymerase from COVID-19 virus. Science, (2020).
  2. C. J. Gordon et al., Remdesivir is a direct-acting antiviral that inhibits RNA-dependent RNA polymerase from severe acute respiratory syndrome coronavirus 2 with high potency. J Biol Chem, (2020).
  3. A. Shannon et al., Remdesivir and SARS-CoV-2: structural requirements at both nsp12 RdRp and nsp14 Exonuclease active-sites. Antiviral Res, 104793 (2020).
  4. T. P. Sheahan et al., An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice. Sci Transl Med, (2020).
  5. J. Grein et al., Compassionate Use of Remdesivir for Patients with Severe Covid-19. N Engl J Med, (2020).
  6. Z. Jin et al., Structure of M(pro) from COVID-19 virus and discovery of its inhibitors. Nature, (2020).

 

View All GVN SARS-CoV-2 Perspectives

Dr. Robert Gallo Exclusive Broadcast Interview with Walter Isaacson of Amanpour & Co.

Can an Oral Polio Vaccine Help Stop COVID-19? 

Please see this just released Associated Press article, “Could old vaccines for other germs protect against COVID-19?” with Dr. Robert Gallo (Institute of Human Virology at the University of Maryland School of Medicine) and Dr. Konstantin Chumakov (U.S. Food and Drug Administration), both of the Global Virus Network (GVN).

Also, watch tonight on PBS at 11 pm EDT and subsequently on CNN International an exclusive broadcast interview by Amanpour & Co: Can an oral polio vaccine help stop the coronavirus? Renowned HIV/AIDS biomedical scientist @DrRobertCGallo explains to @WalterIsaacson why he believes it can be used as emergency, short-term protection. @AmanpourCoPBS

UPDATE: Watch full interview between Amanpour & Co.’s Walter Isaacson and Dr. Robert Gallo here.

You can find additional, recent articles on our GVN SARS-CoV-2 page.

Media Contact:

Nora Samaranayake
Public Relations Senior Advisor
Global Virus Network (GVN)
725 West Lombard St.
Baltimore, MD 21201
443-823-0613
nsamaranayake@gvn.org (email is preferable)

Global Virus Network’s Institute of Human Virology and Italian Scientists Identify Unique Mutations in SARS-CoV-2 Found in Europe and North America

BALTIMORE, MD, April 9, 2020: The Institute of Human Virology (IHV) at the University of Maryland School of Medicine, a Global Virus Network (GVN) Center of Excellence, and scientists from Trieste, Italy announced today the characterization of a novel mutation in the RNA polymerase of certain viral strains of SARS-CoV-2 carried by patients located in Europe and North America. In addition, different patterns of mutations were identified in viral strains corresponding to different geographical areas. The data were obtained by analyzing more than 200 widespread full-length genomic sequences from the National Center for Biotechnology Information (NCBI) and the Global Initiative on Sharing All Influenza Data (GISAID) databases from December 2019 to March 2020.

“We are pleased to collaborate with colleagues in Trieste, and work within the framework of the Global Virus Network, to identify SARS-CoV-2 mutations and their implications in the pandemic, and to advise for therapeutics and vaccine development,” said Robert Gallo, MD, The Homer & Martha Gudelsky Distinguished Professor in Medicine, Co-Founder and Director, Institute of Human Virology (IHV) at the University of Maryland School of Medicine and Co-Founder and Chairman of the International Scientific Leadership Board of the Global Virus Network (GVN).

The findings show that SARS-CoV-2 is quickly evolving and different European, North American and Asian strains may coexist, however, more research is needed to identify the biological significance of these mutations.

“We need to understand the biological and medical significance of the mutations,” said Davide Zella, PhD, Assistant Professor of Biochemistry and Molecular Biology, Institute of Human Virology at the University of Maryland School of Medicine and member, Global Virus Network. “We will continue to collaborate with our Italian colleagues to identify viral mutations in this region.”

“We are excited by these results as they can be applied to improve diagnostic tools to better detect this virus,” said Rudy Ippodrino, PhD, Chief Scientific Officer of Ulisse Biomed, Trieste, Italy.

The data were submitted to, and preprinted by, the Journal of Translational Medicine.

About the Institute of Human Virology

Formed in 1996 as a partnership between the State of Maryland, the City of Baltimore, the University System of Maryland and the University of Maryland Medical System, IHV is an institute of the University of Maryland School of Medicine and is home to some of the most globally-recognized and world-renowned experts in all of virology. The IHV combines the disciplines of basic research, epidemiology and clinical research in a concerted effort to speed the discovery of diagnostics and therapeutics for a wide variety of chronic and deadly viral and immune disorders – most notably, HIV the virus that causes AIDS. For more information, www.ihv.org and follow us on Twitter @IHVmaryland.

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 53 Centers of Excellence and 9 Affiliates in 32 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
443-823-0613
nsamaranayake@gvn.org

Editorial from Dr. Christian Brechot and Dr. Robert Gallo

The SARS-CoV-2 epidemic is spreading and has become a pandemic with a major impact on national health systems and economics, as well as population behaviors. Delineating the future of the pandemic expansion and the geographical areas which will be hit has important consequences as to the capacity to be prepared and take adequate measures to curb the viral dissemination. The progress of science and in particular of mathematical modeling has now offered this possibility. The Global Virus Network, with its fifty four research centers worldwide, has been supporting such initiative. In the posted article from Dr Mohammad M. Sajadi and Dr. Anthony Amoroso, working at the Institute of Human Virology and Global Virus Network, University of Maryland, and other colleagues, the scientists suggest that weather modeling can explain the spread of the virus until now, and that it may be possible to predict the regions most likely to be at higher risk of significant community spread of COVID-19 in the upcoming weeks. This might allow to better focus the public health efforts on surveillance and containment. Clearly, beside climate variables, there are multiple factors to be considered when dealing with a pandemic, such as human population densities and human factors, viral genetic evolution and pathogenesis. Thus those predictions should be considered with caution. Yet this work exactly illustrates how networking activities and science, as provided by the Global Virus Network, can contribute to curbing the infectious threats.

 

Robert Gallo

Co-Founder & International Scientific Advisor, Global Virus Network

Co-founder & Director, Institute of Human Virology at the University of Maryland School of Medicine

 

Christian Bréchot

President Global Virus network

Professor University of South Florida

ENHANCED MODEL FOR MONITORING ZONES OF INCREASED RISK OF COVID-19 SPREAD

Research By GVN Scientists Establishes Link Between Temperature, Latitude, Spread & Seasonality

Baltimore, MD, March 10, 2020:  Scientists affiliated with the Global Virus Network (GVN), the worldwide coalition of preeminent virologists engaged in the preparedness, defense and first research response to emerging, existing and unidentified viruses that pose a clear and present threat to public health, have determined that temperature and latitude may have a direct link to the spread and seasonality of COVID-19.  The analysis was conducted by Drs. Mohammad M. Sajadi, MD, and Anthony Amoroso, MD, in conjunction with the Institute of Human Virology at the University of Maryland and Global Virus Network.  Their paper (https://bit.ly/3cMhQ43), “Temperature and Latitude Analysis to Predict Potential Spread and Seasonality for COVID-19” has been made publicly available at the Elsevier’s SSRN site (https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3550308).  Researchers from University of Maryland College Park, Shiraz University of Medical Sciences in Shiraz, Iran, and Shaheed Beheshti University of Medical Sciences in Tehran, Iran also participated in this study.

 

Figure. World 1000hPa temperature map March 2019-April 2019 showing at risk zone. Color gradient indicates 1000hPa temperatures in degrees Celsius. Tentative zone at risk for significant community spread in the near-term include land areas within the light green bands, outlined in dark black (showing 5-10°C zone based on 2019 data). Predicted area is up to 11°C (slightly more south, not shown), and will change based on actual average temperatures during this time period. Image from Climate Reanalyzer (https://ClimateReanalyzer.org), Climate Change Institute, University of Maine, USA.

“Through this extensive research, it has been determined that weather modeling could potentially explain the spread of COVID-19, making it possible to predict the regions that are most likely to be at higher risk of significant community spread in the near future,” said Robert C. Gallo, MD, Co-founder & Director, Institute of Human Virology at the University of Maryland School of Medicine and Co-Founder and Chairman of the International Scientific Leadership Board of the GVN.  Dr. Gallo is also The Homer & Martha Gudelsky Distinguished Professor in Medicine and Director, Institute of Human Virology at the University of Maryland School of Medicine, a GVN Center of Excellence.  “In addition to climate variables, there are multiple factors to be considered when dealing with a pandemic, such as human population densities, human factors, viral genetic evolution and pathogenesis.  This work illustrates how collaborative research can contribute to understanding, mitigating and preventing infectious threats.”

To date, COVID-19, caused by SARS-CoV-2, has established significant community spread in cities and regions along a narrow east and west distribution, roughly along the 30-50 N” corridor at consistently similar weather patterns (5-11 degrees C and 47-79% humidity).  The GVN’s simplified weather model illustrates the regions that are potentially at higher risk of significant community spread of COVID-19 in the coming weeks, allowing for concentration of public health efforts on surveillance and containment.

“The research conducted by Drs. Mohammad M. Sajadi, MD, and Anthony Amoroso, MD, suggests that overall, human coronaviruses (HCoV-229E, HCoV-HKU1, HCoV-NL63 and HCoV-OC43), which usually lead to common cold symptoms, have been shown to display strong winter seasonality between December and April, and are undetectable in summer months in temperate regions,” said Dr. Christian Bréchot, MD, PhD, President of the GVN, and a Professor at the University of South Florida.  “Based upon the analysis, and assuming the virus doesn’t continue to mutate, we would expect that COVID-19 will diminish considerably in affected areas (above the 30-degree N”) in the coming months, however, the virus could survive at low levels in tropical regions and begin to rise again in the late fall and winter in temperate regions in the upcoming year. We will continue to monitor closely and provide real-time updates as developments and information warrant.”

“Based on what we have documented so far, it appears that the virus has a harder time spreading between people in warmer, tropical climates,” said study leader Mohammad Sajadi, MD, Associate Professor of Medicine at the IHV in UMSOM and a member of GVN. “That suggests once average temperatures rise above 12 degrees Celsius and higher (54 degree Fahrenheit and higher), the virus may be harder to transmit, but this is still a hypothesis that requires more data.”

The spread of SARS-CoV-2 has reached pandemic level, with a major impact on national health systems, economics and population behaviors.  Delineating and understanding the future of the pandemic expansion and geographical areas affected has important consequences in preparation and impacting the viral dissemination.  The GVN is committed to advancing knowledge about how to identify and diagnose pandemic viruses, mitigate and control how such viruses spread and make us sick, as well as to catalyze and facilitate the development of drugs, therapeutics, treatments and vaccines to combat them.  For more information on the GVN, please visit: www.gvn.org.

# # #

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 53 Centers of Excellence and nine Affiliates in 32 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
nsamaranayake@gvn.org

Global Virus Network (GVN) Coordinates Efforts Between Top International Experts Researching COVID-19

The GVN Is Connecting Academia, Governments, Public Health Organizations and Industry to Advance the Response for COVID-19 and Prepare for the Next Outbreak

Baltimore, Maryland, USA, February 18, 2020:  The Global Virus Network (GVN), representing 53 Centers of Excellence and 9 Affiliates in 32 countries comprising foremost experts in every class of virus causing disease in humans and some animals, is holding regular strategic discussions with its members regarding the COVID-19 outbreak, which originated in Wuhan, China this past December.  The GVN, among other critical tasks, is forming subcommittees to make scientific recommendations requested of the network.

“GVN is serving as an information hub, not just for its Centers and Affiliates, but for public health entities and some industry leaders,” said Christian Bréchot, MD, PhD, President of the GVN, and a Professor at the University of South Florida.  “We will be providing recommendations and suggested guidelines for researching COVID-19 in laboratories worldwide, while working with organizations such as the China CDC and Africa CDC as well as companies with scientifically-proven products for testing.”

COVID-19 has spread to other global regions, including Hong Kong, Macao, Taiwan, Australia, Belgium, Cambodia, Canada, Egypt, Finland, France, Germany, India, Italy, Japan, Malaysia, Nepal, Philippines, Russia, Singapore, Spain, Sri Lanka, Sweden, Thailand, The Republic of Korea, United Arab Emirates, United Kingdom, United States and Vietnam.  As of Tuesday morning, February 18, there are more than 73,000 infected around the world and at least 1,873 dead, including five deaths outside of mainland China.  The numbers are likely higher.

“We have one of twelve antibodies against MERS and have submitted a grant to the European Union (EU) to study cross-reactivity and advance a SARS-2/coronavirus vaccine candidate,” said Ab Osterhaus, PhD, DVM, Director of The Research Center for Emerging Infections and Zoonosis (RIZ) at the University of Veterinary Medicine in Hannover, Germany, a Center Director of the GVN, and CEO of Artemis One Health Foundation, Germany.  “At the EVAg meeting I am attending now, we are sharing information about an EU repository for the virus and we look forward to extending accessibility of the virus worldwide.”

“We have been involved in setting up the first diagnostics and helping countries establish this for case finding, as the most urgent need,” said Marion Koopmans, DVM, PhD, Head of the Department of Virosciences of Erasmus MC in Rotterdam, Netherlands, who is director of its GVN Center of Excellence, and a worldwide reference in zoonotic viral diseases and emerging viruses.  “With an EU network of more than 800 hospitals, we are preparing for observational studies and clinical trials, so that we may start enrolling patients if the outbreak grows further outside of China.  Our research agenda includes addressing some key questions about risk factors and studying pathogenesis and immune response in the European population.  Further, we have an interesting reference database of data and samples from patients with different human coronaviruses from previous years, coupled with animal infection experiments to study pathogenesis and transmissibility of the new coronavirus. Lastly, our animal work also involves vaccine evaluation and therapeutic antibody studies.”

Dr. Koopmans attended the recent World Health Organization (WHO) meeting convened last week to address COVID-19.  This was the second time that the WHO convened scientists from across the globe to receive guidance from the scientific community during an acute outbreak. The meeting identified essential knowledge gaps and existing, ongoing research. Part of the meeting was dedicated to defining key priorities, which will be presented to a consortium of funders. As scientific advisor of both the WHO R&D Blueprint and GLOPID-R, Dr. Koopmans notes, “it is fascinating to see how these new coordination mechanisms work. Compared with the Ebola outbreak in West Africa, the response has been much faster, and prepared through the WHO Blueprint. It now is up to the scientific community to listen to the research needs, seek collaboration and share essential data immediately.”

“We are working with the GVN and Dr. Stacey Schultz-Cherry of St. Jude to submit a grant to the U.S. National Institutes of Health to focus on an animal model study of COVID-19,” said Elodie Ghedin, PhD, Professor of Biology and Global Public Health at New York University.  “In collaboration with Dr. Michael Schatz at Johns Hopkins, we have also contributed to developing a new virus genomic sequence assembly application (iGenomics) that can be used with an iPhone in the field.”

“We are working on several projects, including a proposal from the EU Commission on animal model testing for antivirals in addition to projects with the government of Spain,” said Joaquim Segalés, DVM, PhD, Researcher from the Centre de Recerca en Sanitat Animal (CReSA), Spain,a GVN Center of Excellence.

“We continue to distribute virus samples internationally and are working to identify the structure of the virus and further genome sequencing,” said Mike Catton, MB BS, FRCPA, Deputy Director of the Doherty Institute in Melbourne, Australia and Member of the GVN.  “We look forward to hearing from GVN’s specialized subcommittee on BSL-3 versus BSL-4 laboratory testing for COVID-19.”

“Singapore is receiving many requests for virus isolates, and we are looking to our GVN colleagues to advise on how best to prioritize distribution,” said Linfa Wang, PhD, Director of the Programme in Emerging Infectious Diseases at Duke-NUS Medical School and a Center Director of the GVN, Singapore.

“We have researchers at the UB GVN Center of Excellence and UB – Roswell Park Drug Development Center with expertise in identifying potential drugs using target molecules and ‘repurposing’ software simulation approaches. Our GVN center can also develop and validate antiviral drug assays and collaborate with industry for bioanalysis and pharmacokinetics of investigational antivirals. The UB GVN Center also has Affiliate Centers in Zimbabwe and Jamaica that can contribute to evaluation of innovative early warning technologies for COVID-19 infection in their regions,” said Gene Morse, PharmD, FCCP, BCPS, a SUNY Distinguished Professor in the UB School of Pharmacy and Pharmaceutical Sciences, Director of the Translational Pharmacology Research Core and UB’s Center for Integrated Global Biomedical Sciences as well as a GVN Center Director.

“Our lab is actively working on COVID-19 researching antiviral screening, monoclonal antibody screening, and vaccine testing, in both cells and mice,” said Mathew Frieman, PhD, Associate Professor of Microbiology and Immunology and Affiliate Member of the Institute of Human Virology at the University of Maryland School of Medicine, a GVN Center of Excellence.  “We have an infectious clone that we hope will be recovered this week in the BSL-3, and then we will be making mutants across many genes in the clone to advance the study of COVID-19.”

“RKI is currently supplying our international partners with coronavirus diagnostics, mainly PCR primers, probes and controls, but also other supplies, if needed,” said Heinz Ellerbrok, PhD, Deputy Head of the Highly Infectious Diseases Unit at the Robert Koch Institute, a GVN Center of Excellence.  “We have started with shipment of PCR sets to Nigeria CDC on the 6th of February. In the meantime, RKI has supported, or is in the process of supporting, 13 partner institutions in 10 different countries, mainly in Africa, including Côte d’Ivoire, Democratic Republic of the Congo, Namibia, and also countries like Sri Lanka and Yemen.”

Media Contact:
Nora Samaranayake, GVN
410-706-8614
nsamaranayake@gvn.org

Global Virus Network (GVN) Convenes Discussions with International Top Experts to Combat Growing Novel Coronavirus Epidemic

The GVN Is Bridging Gaps in the Global Emergency Response and Serving as a “Go-To” Resource for Members Needing Assistance in Obtaining and Disseminating Cutting-Edge Scientific Research

Baltimore, Maryland, USA, February 6, 2020:  The Global Virus Network (GVN), representing 53 Centers of Excellence and 9 Affiliates in 32 countries comprising foremost experts in every class of virus causing disease in humans and some animals, is holding regular strategic discussions with its members regarding the growing novel coronavirus, known as 2019-nCoV, which originated in Wuhan, China this past December.  The GVN has identified areas to support its Centers and work with international organizations addressing the growing epidemic.

“GVN Centers of Excellence and Affiliates, with strong working relationships among them, are poised to engage in any outbreak situation by providing the world’s only network of top basic virologists from around the globe covering all classes of human viral threats,” said Christian Bréchot, MD, PhD, President of the GVN, and a Professor at the University of South Florida.  “Many members of the GVN are initiating various projects regarding diagnostics, vaccines and therapeutics to combat this rapidly expanding, novel, outbreak.  However, there are still resource needs and information gaps that need to be filled, and GVN is helping to serve as that important resource. In particular, we have engaged GVN Africa to foster collaborations on diagnostics and other important resource needs.”

“We are organizing a workshop for the diagnosis of 2019-nCoV in Dakar for 15 countries in a joint partnership with Africa Centres for Disease Control and Prevention (Africa CDC) in collaboration with the World Health Regional Office for Africa and the West African Health Organization before the epidemic arrives,” said Amadou Alpha Sall, PhD, General Administrator, Institut Pasteur in Dakar, the region’s top biomedical research facility, and Member, Global Virus Network (GVN).  “We are contributing to build ‘the Africa We Want’ in 2063 Africa agenda, while making sure that we anticipate the threat rather than reacting to it.  This is a new model of work for Africa under the leadership of Africa CDC catalyzed by Ebola and other outbreaks that may change the public health practice in Africa in the coming years.”

2019-nCoV has spread to other global regions, including Hong Kong, Macao, Taiwan, Australia, Belgium, Cambodia, Canada, Finland, France, Germany, India, Italy, Japan, Malaysia, Nepal, Philippines, Russia, Sri Lanka, Singapore, South Korea, Spain, Sweden, Thailand, The Republic of Korea, United Arab Emirates, United Kingdom, United States and Vietnam.  As of Thursday morning, February 6, there are over 28,000 infected and more than 560 dead, while the rest of the world reports more than 260 confirmed cases and two deaths outside of mainland China.  The numbers are likely higher.

On January 29, The Peter Doherty Institute for Infection and Immunity (Doherty Institute), a GVN Center of Excellence, in Melbourne announced that, for the first time outside of China, they successfully grew 2019-nCoV from a patient sample in the laboratory and were the first to share the virus with public health laboratories globally and the World Health Organization (WHO). This provides those laboratories, including those within the GVN, with crucial information to help combat the virus.

Mike Catton, MB BS, FRCPA, Deputy Director of the Doherty Institute and Member of the GVN, said that possession of a virus isolate extended what could be achieved with molecular technology in the fight against this virus.

The Doherty Institute-grown virus is expected to be used to generate an antibody test, among other uses, which allows detection of the virus in patients who haven’t displayed symptoms and were therefore unaware they had the virus.

“An antibody test will enable us to retrospectively test suspected patients so we can gather a more accurate picture of how widespread the virus is, and consequently, among other things, the true mortality rate,” said Dr. Catton.

On January 23, after Chinese researchers published the sequence of 2019-nCoV, a GVN partner, the Coalition for Epidemic Preparedness Innovations (CEPI), announced that it will fund three vaccine initiatives with $12.5 million, including GVN Center of Excellence, the Australian Infectious Diseases Research Centere at the University of Queensland (UQ). Further, on February 3, CEPI and GSK announced that GSK will make its established pandemic vaccine adjuvant platform technology available to enhance the development of an effective vaccine against 2019-nCoV. Adjuvants are added to a vaccine to boost the immune response to produce more antibodies and longer-lasting immunity, thus minimizing the dose of antigen needed.

“The University of Queensland’s ‘molecular clamp technology’ provides stability to the viral protein that is the primary target for our immune defense,” said Paul Young, PhD, Head of the School of Chemistry and Molecular Biosciences at UQ, Australia and Member of the GVN.  “The technology has been designed as a platform approach to generate vaccines against a range of human and animal viruses and has shown promising results in the laboratory targeting viruses such as influenza, Ebola, Nipah and MERS coronavirus. The availability of the GSK adjuvant will enable us to carry out important pre-clinical experiments designed to assess vaccine effectiveness.”

Other GVN researchers are sourcing their MERS and SARS coronavirus expertise to advance vaccine development for this new outbreak. “With our experience and novel contributions to the MERS and SARS outbreaks as well as the deadly zoonosis influenza viruses, H7N7 and H5N1, we are working to develop a vaccine against this new, novel coronavirus,” said Ab Osterhaus, PhD, DVM, Director of the The Research Center for Emerging Infections and Zoonosis (RIZ) at the University of Veterinary Medicine in Hannover, Germany, a Center Director of the GVN, and CEO of Artemis One Health Foundation, Germany. “Specifically, we are poised to study T-Cell and IgM antibody response using our expertise in animal models.”

Linfa Wang, PhD, Director of the Programme in Emerging Infectious Diseases at Duke-NUS Medical School and a Center Director of the GVN, Singapore, is developing diagnostics for 2019-nCoV with collaborators in China. Dr.  Wang, who sequenced and named Australia’s bat-borne Hendra virus more than 25 years ago, has obtained multiple isolates of the virus, and is focused on studying serology and cross-reactivity and contamination on diagnostics. Dr. Wang believes the deadly new coronavirus “appears to be more infectious than the 2003 SARS coronavirus.”  Further he warns, “Despite the possibility for criticisms of an overreaction, it is imperative that we act quickly and effectively, as the alternative of an underreaction could potentially lead to more deaths worldwide.”

“We are funneling resources towards this new novel virus research on animal infection, transmission and reservoirs,” said Joaquim Segalés, DVM, PhD, Researcher from the Centre de Recerca en Sanitat Animal (CReSA), Spain and a Center Director of the GVN.  “We also have a number of reagents against MERS available, and are waiting to receive isolates of the virus, hopefully from our GVN colleagues.”

“Our GVN colleagues in Melbourne at the Doherty Institute are shipping a sample of this new novel virus as we speak,” said Johan Neyts, PhD, Professor of Virology, Rega Institute for Medical Research at the University of Leuven and a Center Director of the GVN.  “We are developing a dual yellow fever/2019-nCoV using our revolutionary Plasmid Launched Live Attenuated Virus (PLAV) technology based. We managed recently to do the same with yellow fever and other viruses such as Lassa and rabies.  Further, using our fully automated high biosafety laboratory, we are leading an intensive research effort to develop therapeutics against 2019-nCoV.”

“The GVN wishes to help and collaborate with other scientists globally, and especially to include the China GVN and China CDC, whose scientists, under the leadership of Dr. George F. Gao, have made important initial contributions to the genomic characterization and epidemiology of this deadly virus,” said Robert Gallo, MD, Co-Founder and Chairman of the International Scientific Leadership Board of the GVN.  Dr. Gallo is also The Homer & Martha Gudelsky Distinguished Professor in Medicine and Director, Institute of Human Virology (IHV) at the University of Maryland School of Medicine, a GVN Center of Excellence.

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 53 Centers of Excellence and 9 Affiliates in 32 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
410-706-8614
nsamaranayake@gvn.org

Global Virus Network (GVN) Experts Combat New Worldwide Coronavirus Outbreak

GVN stands by China and relevant international organizations to support efforts to mitigate the new strain of coronavirus, named 2019-nCoV

Baltimore, Maryland, USA, January 30, 2020: As airlines suspend flights, countries evacuate citizens from China and nearly 60 million Chinese experience a lockdown, the Global Virus Network (GVN), representing 53 Centers of Excellence and 9 Affiliates in 32 countries comprising foremost experts in every class of virus causing disease in humans and some animals, will stand by China and relevant international organizations to support efforts to mitigate the new strain of coronavirus, named 2019-nCoV, originating from Wuhan, China. The outbreak, which causes respiratory illness, originated in a seafood and meat market in Wuhan, a city of 11 million, and likely jumped to humans from bats. 2019-nCoV has spread to other global regions, including Hong Kong, Macau, Taiwan, Australia, Cambodia, Canada, Finland, France, Germany, India, Japan, Malaysia, Nepal, Philippines, Sri Lanka, Singapore, Thailand, The Republic of Korea, United Arab Emirates, United States and Vietnam. As of Thursday, January 30, 6:00 AM ET according to Chinese authorities there are nearly 8,000 infected and 170 dead, while the rest of the world reports more than 110 confirmed cases outside of China.

“Many members of the GVN are initiating various projects regarding diagnostics, vaccine and therapeutics to combat this rapidly expanding, novel, outbreak,” said Christian Bréchot, MD, PhD, President of the GVN, and a Professor at the University of South Florida. “We support current organizations such as the World Health Organization and stand ready to serve as global first-responders to this dangerous virus and operate as an international clearinghouse to educate, inform and disseminate critical information to governments, health organizations, healthcare practitioners and the public-at-large.”

On January 23, after Chinese researchers published the sequence of 2019-nCoV, a GVN partner, the Coalition for Epidemic Preparedness Innovations (CEPI), announced that it will fund three vaccine initiatives with $12.5 million. One of those recipients includes GVN Center of Excellence, the Australian Infectious Diseases Research Centere at the University of Queensland (UQ).

“The University of Queensland’s molecular clamp technology provides stability to the viral protein that is the primary target for our immune defense,” said Keith Chappell, PhD, Senior Research Fellow in the School of Chemistry and Molecular Biosciences at UQ, Australia. “The technology has been designed as a platform approach to generate vaccines against a range of human and animal viruses and has shown promising results in the laboratory targeting viruses such as influenza, Ebola, Nipah and MERS coronavirus.”

Other GVN researchers are sourcing their MERS and SARS coronavirus expertise to advance vaccine development for this new outbreak. “With our experience and novel contributions to the MERS and SARS outbreaks as well as the deadly zoonosis influenza viruses, H7N7 and H5N1, we are working to develop a vaccine against this new, novel coronavirus,” said Ab Osterhaus, PhD, DVM, Director, The Research Center for Emerging Infections and Zoonosis (RIZ), University of Veterinary Medicine in Hannover, Germany, Center Director, Global Virus Network (GVN) CEO, Artemis One Health Foundation, Germany.

Linfa Wang, PhD, Director, Programme in Emerging Infectious Diseases at Duke-NUS Medical School, Center Director, Global Virus Network (GVN), Singapore, is developing diagnostics for 2019-nCoV with collaborators in China. Dr. Wang, who sequenced and named Australia’s bat-borne Hendra virus more than 25 years ago, believes the deadly new coronavirus “appears to be more infectious than the 2003 SARS coronavirus.” Further he warns, “Despite the possibility for criticisms of an overreaction, it is imperative that we act quickly and effectively, as the alternative of an underreaction could potentially lead to more deaths worldwide.”

“The use of human ACE2 2019-nCoV is now confirmed by multiple actual viral isolates from the laboratory of Zhengli Shi, PhD, who is the director of center for infectious disease at Wuhan Institute of Virology, Chinese Academy of Sciences, and who was responsible for identifying many of the bat SARS-like CoV in the past ten years,” said Benhur Lee, MD, Professor of Microbiology, Member, Global Virus Network (GVN), Icahn School of Medicine at Mount Sinai, USA. “I believe that all symptomatic people with or without cough is potentially contagious with this new novel virus as Shi’s research shows virus-specific IgM being detected in patients one week post-symptoms onset; the finding that most patients have neutralizing IgG+ antibodies by two weeks post-symptoms; patients as having cough/chest congestion with high virial loads; and, one 2019-nCoV virus positive patient as having fever as the only symptom.”

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 53 Centers of Excellence and 9 Affiliates in 32 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
410-706-8614
nsamaranayake@gvn.org