: TNX-1800 (COVID-19 Vaccine)

TNX-1800 (COVID-19 Vaccine)

Scientific Rationale for TNX-1800 as a vaccine for COVID-19

TNX-1800 is being developed by Tonix Pharmaceuticals to support the development of a vaccine to protect against the COVID-19. TNX-1800 is based on Tonix’s proprietary horsepox vaccine platform. It is believed that horsepox has the potential to serve as a vector for vaccines to protect against other infectious agents. The research will develop and test a potential horsepox vaccine that expresses protein from the virus that causes COVID-19 to protect against the disease.

About TNX-801* and TNX-1800*

TNX-801 is a live virus vaccine based on synthesized horsepox1,2. TNX-1800 is a modified horsepox virus that is designed to express a protein from the virus that causes COVID-19, which is known as SARS-CoV-2. Molecular analysis suggests that TNX-801 has relatively “complete” left and right inverted terminal repeats (ITRs) while different vaccinia isolates have a variety of deletions in the left and right ITRs. Therefore, TNX-801 has additional genes, relative to vaccinia vaccines, that may play roles in host immune interactions and one or more of such proteins may serve as antigens for protective immunity. Molecular analysis also shows that horsepox is closer than modern vaccines in DNA sequence to the vaccine discovered and disseminated by Dr. Edward Jenner2,3,4. No new gene elements were added to the natural isolate and the small plaque size in culture appears identical to the U.S. Centers for Disease Control publication of the natural isolate5. Relative to vaccinia, horsepox has substantially decreased virulence in mice1. TNX-801 vaccinated macaques showed no overt clinical signs after monkeypox challenge6.

*TNX-801 and TNX-1800 are in the pre-IND stage and have not been approved for any indication.

About Orthopoxvirus Vectors

Horsepox and vaccinia are closely related orthopoxvirus that are believed to share a common ancestor. The name “horsepox” was derived from the animal from which the virus was isolated. The natural host is presumed to be wild rodents. The name “vaccinia” is a term that is applied to a group of related vaccine viruses that were industrially produced by infecting cows. The terms “vaccinia” and “vaccine” were originally coined by Dr. Edward Jenner (derived from the Latin “vacca” for “a cow”) in his description of an illness in cows (cowpox) that was transferred inadvertently by human hands from horses to cows and from cows to human hands. Jenner was the first to use infectious matter (vaccinia or vaccine) from cowpox to elicit protective immunity to smallpox by intentional “vaccination”. Although horsepox is not considered to be a vaccinia, modern DNA analysis reveals more variation between different vaccinia strains than between horsepox and certain vaccinia strains. Live replicating orthopoxvirus, like vaccinia or horsepox, can be engineered to express foreign genes and have been explored as platforms for vaccine development because they possess; (1) large packaging capacity for exogenous DNA inserts, (2) precise virus-specific control of exogenous gene insert expression, (3) lack of persistence or genomic integration in the host, (4) strong immunogenicity as a vaccine, (5) ability to rapidly generate vector/insert constructs, (6) readily manufacturable at scale, and (7) ability to provide direct antigen presentation.

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What makes TNX-1800 unique?

TNX-1800, as a horsepox vaccine, has potential advantages over vaccinia-based vaccines, including:

  • Maintains strong immunogenicity with potentially improved tolerability
  • Relative to non-replicating vaccinia, horsepox’s replication in human cells provides direct antigen presentation by Class I MHC
  • Horsepox may behave differently as a vector, in part because of its different repertoire of genes that modulate immune responses and host range
  1. Noyce RS, et al. (2018) PLoS One. 13(1):e0188453
  2. Tulman ER, et al. (2006) J Virol. 80(18):9244-58.PMID:16940536
  3. Schrick L et al. N Engl J Med. (2017) 377:1491.
  4. Qin et al. J. Virol. 89:1809 (2015).
  5. Trindale GS et al. Viruses (2016) (12). pii: E328. PMID:27973399
  6. Noyce, RS, et al. Synthetic Chimeric Horsepox Virus (scHPXV) Vaccination Protects Macaques from Monkeypox* Presented as a poster at the American Society of Microbiology BioThreats Conference - January 29, 2020, Arlington, VA. (https://content.equisolve.net/tonixpharma/media/10929ac27f4fb5f5204f5cf41d59a121.pdf )