Vaxart’s Oral COVID-19 Vaccine Candidate Induces Potent Systemic and Mucosal Immune Responses in Preclinical Studies
- Category: Vaccines
- Published on Tuesday, 08 September 2020 17:43
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Triggering mucosal immunity may be crucial for effective protection against SARS-CoV-2 infection and transmission
Vaxart’s oral tablet vaccine can overcome major challenges of injectable vaccines
SOUTH SAN FRANCISCO, CA, USA I September 08, 2020 I Vaxart, Inc. (NASDAQ: VXRT), a clinical-stage biotechnology company developing oral recombinant vaccines that are administered by tablet rather than by injection, today announced pre-publication of a manuscript titled “Preclinical studies of a recombinant adenoviral mucosal vaccine to prevent SARS-CoV-2 infection.” The manuscript describes the pre-clinical development of a SARS-CoV-2 (COVID-19) vaccine based on Vaxart’s oral adenovirus platform and is available on an online preprint server at https://biorxiv.org/cgi/content/short/2020.09.04.283853v1.
“Vaxart is developing an oral COVID-19 vaccine that will address many of the key challenges of injectable vaccines,” said Andrei Floroiu, chief executive officer of Vaxart. “Cold storage distribution and the need for medical personnel as well as having to travel to vaccination sites and dislike of needles pose significant barriers to the vaccine uptake required for successful mass vaccination campaigns. We believe our room temperature stable, easy to administer oral vaccine provides a unique solution that overcomes these important difficulties. We look forward to advancing our COVID-19 vaccine candidate into the clinic.”
- Immunization with the vaccine candidate induced IgA response in the lungs of animals, which is indicative of a mucosal immune response. Of particular note, neutralizing antibodies in the lungs were observed at a very high percentage of the total antibody response.
- Immunization with our vaccine candidate expressing full length S and N proteins induced IgG responses in a dose-dependent manner.
- Antigen-specific CD4+ and CD8+ T cells were induced at both low and high doses.
- Vaccine administration induced only low levels of IL-4 production, suggesting little risk of vaccine- dependent disease enhancement.
Sean Tucker, Ph.D., chief scientific officer of Vaxart, commented, “The data from these studies suggest that our vaccine candidate is capable of inducing immunogenicity on three levels: first, to induce potent serum neutralizing antibodies to the viral S protein, second to induce a mucosal immune response, and third to induce T cell responses. As we continue to learn more about COVID-19, there is a growing body of evidence that mucosal immunity may become a key factor for the development of an efficacious vaccine. Both mucosal IgA and mucosal T cells have been shown to contribute to sterilizing immunity in other respiratory diseases. Importantly, while systemic immunity is important for controlling the development of illness, it has been suggested that mucosal immunity may be essential for blocking transmission which will be crucial for an effective vaccine campaign. We believe this will be essential in reducing infection rates and eventually eradicating COVID-19 globally.”
The study was designed to assess the relative immunogenicity of four candidate vaccines expressing multiple combinations of the spike (S) and nucleocapsid (N) proteins of the SARS-CoV-2 virus in a standard mouse model. While all candidates demonstrated the ability to elicit a strong immune response, the most successful candidate contained the full length S and N proteins. While the S protein is responsible for receptor binding, membrane fusion, and tissue tropism and a major target for neutralizing antibodies, targeting full length S protein in combination with N protein may prevent future vaccine-driven escape due to the accumulation of mutations in the S protein. The inclusion of N protein in the vaccine candidate provides additional conserved T epitopes. Further, the induction of polymeric IgA at mucosal surfaces may be superior for generating neutralizing antibodies against divergent viruses.
Vaxart is a clinical-stage biotechnology company developing a range of oral recombinant vaccines based on its proprietary delivery platform. Vaxart vaccines are administered using convenient room temperature-stable tablets that can be stored and shipped without refrigeration and eliminate the risk of needle-stick injury. Vaxart has demonstrated that its proprietary tablet vaccine delivery platform is suitable to deliver recombinant vaccines, positioning the company to develop oral versions of currently marketed vaccines and to design recombinant vaccines for new indications. Its development programs currently include tablet vaccines designed to protect against coronavirus, norovirus, seasonal influenza and respiratory syncytial virus (RSV), as well as a therapeutic vaccine for human papillomavirus (HPV), Vaxart’s first immuno-oncology indication. Vaxart has filed broad domestic and international patents covering its proprietary technology and creations for oral vaccination using adenovirus and TLR3 agonists.