SARS-CoV-2 Updates – Vaccines

Other SARS-CoV-2 updates

Academia

GVN Centers

University Queensland, Australia, Paul Young

Vaccine Animal Models

CEPI Funded to accelerate the Clamp Trimer vaccine-modify S-protein.
Attained immunization in mice studies, toxicity studies, and planned working with CSIRO-animal model

1,000 doses by end of June; GSK, Seqirus and Dynavax offered adjuvants for their Animal Models. Effort to expedite, ’emergency’ Phase-1 and Large-scale production
Demonstrate regulatory Agencies Clamp Trimer does not enhance pulmonary disease in
Non-human primate, (NHP) models. Dr. Albert Osterhaus to assist.

https://stories.uq.edu.au/research/impact/2020/uq-responds-to-coronavirus-outbreak/index.html

Matthew Frieman, University of Maryland School of Medicine, Baltimore

Animal Models

nCoV and SARS viruses and other reagents currently available
SARS, MERS and nCoV reverse genetic clones and human isolates
Vaccines- working with Novavax on other vaccine platforms.
BSL2 Coronaviruses (OC43, 229E)
Rapid neutralizing antibody assays using micro neutralization
Mammalian plasmids expression of SARS, MERS and nCoV (soon)
Drug screening: several hundred FDA approved and novel compounds identified in collaboration with several companies and the Gates Foundation. Later, tested in our mouse model for efficacy.
Mouse models for SARS, MERS and nCoV (in progress)
Antibodies: We are working with Regeneron on their monoclonal antibody isolation and validation, and developing a mouse model for infection and protection assays.
Generation of viruses and other reagents planned/ in progress. Infectious clones of nCoV with variants, deletions, reporter inserts. Infectious clone: JCVI collaborations on the creation of an infectious clone for Wuhan-1 strain and deletion viruses to characterize accessory protein function.
Series of viruses that delete individual viral proteins and replacing them with fluorescent marker genes to allow for detection of the virus in cells easier. This will speed drug and antibody screening significantly, and gene function characterization in the virus both in vitro and in vivo.
Cross-reactivity assessments planned/in progress. Testing anti-SARS and anti-MERS monoclonal and polyclonal sera for cross reactivity with nCoV live virus

IRTA-CReSA, Barcelona, Spain, Joaquim Segales

MERS re-agents animal model in mice, possible larger animals
Animal infection, transmission and reservoirs.
At stage acquiring biosecurity & ethical permissions; propagating the virus to get a right inoculum. We expect pigs study, April 6th,

http://www.irta.cat/en/irta-irsicaixa-and-barcelona-supercomputing-center-collaborate-to-find-a-coronavirus-treatment-and-vaccine/

University of Veterinary Medicine Hannover, TiHO, Germany, Ab Osterhaus

Rapid antibody production and T-Cell response; Preliminary, using animal models
Investigate MERS/SARS Cross-reactivity
SARS-2/Corona virus vaccine-IgG-dependent enhancement, (ADE) prior to Phase-1. To test adverse effects and toxicity
CEPI to support monkey models

https://www.tiho-hannover.de/kliniken-institute/forschungszentrum-fuer-infektionsmedizin/management-and-research-groups/ag-osterhaus/project-leader/

New York University, Elodie Ghedin

Covid-19 Supplemental flu transmission grant in collaborations with The GVN and University of Georgia using ferret animal models.
New app-based, rapid, transportable, virus genome assembly program for field work

Industry

Sanofi

rDNA Platform
Creates an exact genetic match of virus surface protein
DNA sequence is then combined into the DNA of the baculovirus
Expression platform-Sanofi’s recombinant influenza product
Used for scaling-up Co-2 antigen
Sustained production-adjuvanted recombinant vaccine: longer lasting immunity and less dose required
Partnership-BARDA

Moderna

Name: mRNA-1273
Collaborators-NIAID/(VRC) and led by UNMC
Encoding for a prefusion stabilizing form of the Spike S protein
Clinical Trials could start, end of April
mRNA mimic the natural infection to stimulate a more potent immune response, combining multiple RNAs in a single vaccine. Expedited through ‘Emergency speed.’ Entered Phase-2, successfully
Testing and regulatory approval, 1 year; 1,000 subjects enrolled

https://investors.modernatx.com/news-releases/news-release-details/moderna-ships-mrna-vaccine-against-novel-coronavirus-mrna-1273

Applied DNA Sciences & Takis Biotech

PCR-produced Linear DNA vaccine 4 Vaccine candidates. Viral Spiked Protein-prevent cell-entry
One of the 4 candidate vaccines targeting the entire spike gene; the remaining 3 are variants based upon epitope mapping (identifying the likely antigenic portions of the protein), and assembling the corresponding parts of the ‘S gene into a new synthetic Linear DNA gene, and codon optimization (to ensure the new LinearDNA vaccine genes are efficiently expressed as proteins, once the genes have been delivered to a small percentage of the nuclei of the patient’s muscle cells.)
Pre-clinical/Animals Testing & regulatory approval, 1 year; 1,000 enrolled
mRNA mimic the natural infection to stimulate a more potent immune response, combining multiple RNAs in a single vaccine

https://adnas.com/pharmaceutical-technology-applied-dna-and-takis-biotech-covid-29-vaccine-candidates/

GSK

COVID-19 S-Trimer/adjuvant
Collaborator-Clover
Large-scale cGMP biomanufacturing capabilities in China
Reduces the amount of vaccine protein required per dose, allowing more vaccine doses
to be produced and therefore contributing to protect more people.
Viral spike (S)-protein construct and completed its gene synthesis. Utilizing its patented
Trimer-Tag© technology. Clover has produced a S-Trimer subunit vaccine that resembles the native trimeric viral spike via a rapid mammalian cell-culture based expression system.

https://www.gsk.com/en-gb/media/press-releases/clover-and-gsk-announce-research-collaboration-to-evaluate-coronavirus-covid-19-vaccine-candidate-with-pandemic-adjuvant-system/

Medicago

High scale-up ability using plants
Pre-clinical-Vaccine candidate
IgM virus-like particles mimic virus form. Empty shells, no genetic information, proteins to replicate. Use copies from recovered people

https://www.businesswire.com/news/home/20200312005345/en/Medicago-Announces-Production-Viable-Vaccine-Candidate-COVID-19

Novavax

CEPI/Emergent BioSolutions for (scale-up)
Proprietary recombinant protein nanoparticle technology platform to generate antigens derived from the coronavirus spike (S) protein. Novavax also expects to utilize its proprietary Matrix-M™ adjuvant with its COVID-19 vaccine candidates to enhance immune responses. Late Spring-Initiation of CTs.
The trimeric S protein of SARS-CoV-2 is responsible for binding to host cell surface receptor ACE2 and subsequent viral entry, making it the primary target antigen for vaccine development.

https://www.globenewswire.com/news-release/2020/03/10/1997798/0/en/Novavax-Awarded-Funding-from-CEPI-for-COVID-19-Vaccine-Development.html

Janssen Pharmaceutical Cos. (Johnson & Johnson):

Preventative-Prezcobix™ (darunavir and cobicistat); Vaccine to be developed with BARDA and Shanghai Public Health Clinical Center and Beth Israel Deaconess medical Center
30 participants study design; Identify at end-of-month vaccine a candidate
Antiviral; Protease Inhibitor | anti-pneumonia
The virologic clearance rate of throat swabs, sputum, or lower respiratory tract secretions at day 7 [ Time Frame: 7 days after randomization ]
or lopinavir-ritonavir combination combined with thymosin a1

https://www.jnj.com/media-center/press-releases/janssen-receives-positive-chmp-opinion-for-symtuza-the-first-darunavir-based-single-tablet-regimen-for-the-treatment-of-hiv

Inovio Pharmaceuticals

DNA vaccine/INO-4800 with Beijing Advance Biotechnology
Molecular Clamp Vaccine
Accelerated timeline; Pre-Trials-April/USA, then China and South Korea and 1M doses year’s end
Only company Phase-2 vaccine MERS-CoV

http://ir.inovio.com/news-and-media/news/press-release-details/2020/Inovio-Collaborating-With-Beijing-Advaccine-To-Advance-INO-4800-Vaccine-Against-New-Coronavirus-In-China/default.aspx

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