EPV-CoV19

EpiVax's T Cell Epitope-Driven vaccine for COVID-19

EPV-CoV19, a peptide-based, epitope driven vaccine candidate, designed using EpiVax’s proprietary iVAX toolkit, a web-based work environment geared for rapid in silico vaccine design. The vaccine will drive a cell-mediated immune response, providing Health Care Workers (HCW) and First Responders with the immune system ‘body armor’ they need to reduce morbidity and mortality. EPV-CoV19 combines short peptide sequences that are conserved in all circulating SARS-CoV-2 genomes, providing broad T cell-mediated protection against all existing SARS-CoV-2 virus strains.

This EPV-CoV19-generated T cell response will protect HCW and First Responders by enabling the immune system to clear the virus, reducing morbidity while also lowering viral titers, should exposure occur.

EpiVax EPV-CoV19 approach

Other COVID-19 vaccine options may become available to HCW and First Responders but vaccine experts have raised concerns about the potential for antibody-dependent exacerbation (ADE) of COVID-19.

In addition to the concern about ADE, neutralizing antibody titers (to SARS-Cov-2) have been shown to be short lived and may only recognize the vaccine strain. SARS-CoV-2 has already established at least two separate clades or strains; cross-protection between known Human Coronavirus spike proteins has been shown to be extremely poor. In contrast to antibody-directed vaccines, EPV-CoV19 will stimulate protective T cell response. EPV-CoV19 will also create long-lasting cellular immunity

An additional unique feature of the EPV-CoV19 program is the availability of no-cost licenses for the vaccine recipe for developing world countries who have GMP facilities for production of the vaccine. EpiVax’s board of directors voted to grant a cost-free license on the EPV-CoV19 vaccine to the GAIA Vaccine Foundation. GAIA Vaccine Foundation is a 501c3 organization whose mission is to “promote the development of globally-relevant, globally-accessible vaccines for infectious diseases that adversely impact persons living in developing world countries.

EPV-CoV19, is ready for production and deployment. A Phase I Trial of EPV-CoV19 will begin in 3 months. The company will apply for Emergency Use Authorization from the FDA and intends to conduct clinical trials in the United States in parallel, with trials at a clinical trial site in West Africa.

Rationale

Concerns about safety of whole protein (Spike) vaccines in the context of COVID-19.

  • Antibodies generated by traditional vaccines could exacerbate disease, if infection does occur.
  • This concept is called Antibody Dependent Exacerbation, ADE.
  • Most large companies are developing vaccines focused on antibody response. These traditional vaccines also take a long time to develop, pre-clinical studies are required, due to safety concerns about the novel delivery platforms.
  • It may be more than a year before such vaccines are available, and the target is the ‘general population’.
  • Safety is a key issue.

Epitope-driven vaccines ‘win’ from the safety and speed perspective.

  • Only small parts of the genome sequence are included in the vaccine and no antibodies would be generated.
  • At EpiVax, this approach has resulted in the development of three epitope-driven vaccines (ID-EDV) that proved protective against viral or bacterial challenge.
  • Protective efficacies of 100% (vaccinia), 90% (H. pylori), and 57% (tularemia) were achieved.
  • Epitope-driven vaccines have a significant advantage over conventional vaccines; the careful selection of the components should diminish undesired side effects such as those observed with whole pathogen and protein subunit vaccines.
  • Speed is of the essence, and GMP peptides can be synthesized and ready for distribution in 2 months, due to new processes developed by EpiVax (EpiVax Oncology).

 

Efficacy

What is a T cell epitope-driven Vaccine and why do healthcare and 1st responders need it:

A Healthcare worker or 1st responder that has T cell defense generated by this vaccine may be infected by COVID-19 but would not die.

All vaccines drive protective immunity using antigens from the pathogen, combined with adjuvant, to generate ‘adaptive immunity’.  Most vaccinologists focus on antibodies, but T cells are critically important to vaccine efficacy. T cells see linear sequences that are presented on the surface of immune system cells that are called antigen presenting cells. These sequences trigger T cell immune response that clears the virus from infected cells.  Two types of T cells are involved. CTL cells are critically important to viral defense by killing infected cells, T helper cells enable the body to make strong CTL and stronger B cells that will then produce antibody defense – usually this occurs days after the viral burden is lowered by CTL.

Case Study: In 2009, the CDC and WHO warned that the emerging 2009 “swine-origin” influenza would be a Pandemic. There was no ‘immune defense’ and they cautioned that a new vaccine was required. EpiVax analyzed the new flu virus and determined that T cell epitopes (sequences) were conserved between the new strain (2009 California) and the previous year’s flu (Brisbane), even though the antibody response would not be conserved. EpiVax predicted that this “Pre-existing T-cell mediated immune memory” would be sufficient to protect most individuals against severe H1N1 2009 pandemic disease (hospitalizations) even though people would still be infected (antibody was not present to protect against infection). Even if infected, they would not have severe disease. This turned out to be true, and it will also be true for COVID-19EPV-COV19 may not protect against infection (antibodies do that), but it would protect against severe disease.

Safety Factors

The design of EPV-COVID-19 incorporates several important safety factors that will facilitate Emergency Use Authorization Approval.

  1. Peptides. Peptide drugs and vaccines are well known, and they are safe. Peptides made synthetically, under “GMP”. Many peptide drugs are in the clinic, and EpiVax uses tools that the FDA knows to improve peptide drug safety. Those tools will be applied to this vaccine.

  2. ADE. There is significant concern that an antibody-driven vaccine could exacerbate infection and lead to worse disease if infection occurs. It is possible that some of the severe lung manifestations (Acute Respiratory Distress Syndrome, ARDS) is due to antibodies against the COVID-19 virus (SARS-CoV-2). This is because antibodies (from a vaccine) could bind the virus, and deliver the virus to target cells, where the virus could multiply. This is called Antibody Dependent Exacerbation (ADE). ADE was observed for the DengVaxia vaccine recently and is known to occur for Coronavirus vaccine (in cats, but has also be observed for MERS and SARS in published studies). A T cell vaccine will never drive ADE. This is a critically important safety factor.
  3. “Human-like” epitopes. All of the T cell epitopes in the vaccine are screened for cross-conservation against the human genome using a tool called JanusMatrix. This significantly reduces the risk of adverse off target effects. The FDA reviewers are already familiar with the concept of human-like epitopes discovered by JanusMatrix and have indicated they agree that this will be a positive factor in the review.
  4. Peptide synthesis impurities are screened in silico. All of the peptide epitopes going into the vaccine will be screened using a different algorithm (WhIM) for potential impurities that could be created in the synthesis process. This is again a unique safety factor. Any impurity that could potentially create an off-target effect will be identified (in silico) and removed (using HPLC).

EpiVax remains dedicated to the global efforts in relief of COVID-19. 

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