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Vaxart COVID-19 Oral Vaccine

4 min read

Authored byStaffUpdated December 1, 2021

Last reviewed December 1, 2021

Fact checked byRobert Carlson, MD + Holly Lutmer PharmDShare

Vaxart COVID-19 Oral Vaccine (VXA-CoV2-1) Description

Vaxart announced an oral COVID-19 vaccine targeting the SARS-CoV-2 coronavirus that causes COVID-19. Vaxart’s oral COVID-19 vaccine triggers mucosal immune responses in humans. Mucosal immunity is believed to be the first defense against airborne viruses, such as coronavirus and flu. It may also be important in reducing viral shedding and preventing transmission.

The oral COVID-19 vaccine targets both the spike protein (S) and nucleoprotein (N). The N protein is more conserved (less prone to mutations) than the S protein, and therefore new viral variants may be less likely to escape protection. The N protein is also a good target for T-cell responses. Potent T-cell responses alone may offer multivariant protection against severe COVID-19 illness.

Vaxart announced it is also advancing an S-only vaccine candidate that may improve antibody responses, including against SARS-CoV-2 variants such as the South African viral strain. This new candidate is expected to generate strong mucosal and serum antibody responses and complement the potent T-cell inducer. In addition, Vaxart has previously shown that a bivalent oral vaccine using its platform can induce immune responses without interference.

Vaxart oral recombinant vaccines are formulated as enterically coated tablets for delivery to the small bowel. The enteric coating protects the active ingredient from the stomach’s acidic environment. By targeting the small bowel, the vaccines engage the gut’s finely-tuned immune system to generate broad systemic and mucosal immune responses for robust, persistent immunity.

Vaxart is currently developing a liquid formulation for young children and adults who cannot ingest tablets. Vaxart vaccines do not contain whole killed or attenuated viruses. No eggs are used in the production process.

Vaxart’s oral vaccines represent a significant advance in vaccination technology. They are designed to generate broad and durable immune responses, including mucosal and systemic reactions. In addition, the oral administration route provides a more efficient and convenient administration method relative to injectable vaccines.

Vaxart COVID-19 Oral Vaccine (VXA-CoV2-1) History

On May 20, 2020, Sean Tucker, Ph.D., chief scientific officer of Vaxart, announced, “In a phase 2 efficacy study, we have demonstrated that our oral H1 flu tablet vaccine protected against influenza infection after just 1-dose. Based on these results, we believe our vaccines are ideal for protecting against mucosal respiratory viruses such as SARS-CoV-2, the virus that causes COVID-19.”

“The results of our recently published influenza challenge study demonstrated that our oral tablet vaccine primarily protects through mucosal immunity, a potential key factor when targeting mucosal pathogens, such as this new coronavirus,” said Sean Tucker, Ph.D. chief scientific officer of Vaxart.

This was a Phase 2 Randomized, Placebo- and Active-Controlled, Human Influenza A/California/04/2009 (H1N1) Challenge Study Following Administration of an Oral H1N1 HA Adenoviral-Vector Based Seasonal Influenza Vaccine and dsRNA Adjuvant (VXA-A1.1) to Healthy Adult Volunteers, which was last updated on July 26, 2018.

On August 6, 2020, Andrei Floroiu, chief executive officer of Vaxart, stated: “We believe the convenience of our oral tablet, coupled with the potential for better protection than that of injectable vaccines due to the activation of mucosal immunity, positions our COVID-19 vaccine as one of the most promising candidates for successful mass vaccination campaigns, both here in the U.S. and abroad.”

On September 6, 2020, the non-peer-reviewed study ‘Preclinical studies of a recombinant adenoviral mucosal vaccine to prevent SARS-CoV-2 infection’ showed immune responses in mice. These researchers stated: ‘We demonstrate that, compared to the expression of the S1 domain or a stabilized spike antigen, the full length, wild-type spike antigen induces significantly higher neutralizing antibodies in the periphery and the lungs, when the vaccine is administered mucosally. In addition, this leading vaccine candidate induced Antigen-specific CD4+ and CD8+ T cells at low and high doses. Therefore, this full-length spike antigen plus nucleocapsid adenovirus construct has been prioritized for further clinical development.’

On October 14, 2020 – Vaxart announced the topline results from its Hamster Challenge Study that all hamsters that received (2) oral doses of COVID-19 vaccine candidate showed no systemic weight loss, a key protection indicator against COVID-19 in this animal model. The study evaluated Vaxart’s recombinant adenoviral vaccine, with doses given at 0 and 4 weeks. Animals were challenged with SARS-CoV-2 at week 8. These topline data demonstrated that all unvaccinated animals lost at least 8% of their body weight, and all showed evidence of lung disease as measured by relative weight gain in the lungs. By contrast, a statistically significant result was that all animals vaccinated with 2-doses of the oral vaccine maintained or gained body weight by the end of the experiment (p<0.001). Additionally, these animals were protected against the lung weight gain seen in the unvaccinated animals (p<0.001).

On February 3, 2021, Sean Tucker, Ph.D., Vaxart’s Chief Scientific Officer, stated in a press release, “Viral variants with altered S proteins are becoming established in the population before the majority of people can be vaccinated. To end the pandemic, the world needs a vaccine that can provide long-lasting protection from emerging strains.”

On May 3, 2021, Vaxart announced it would advance three oral tablet COVID-19 vaccine candidates to the clinic: VXA-CoV2-1 (includes both the S and the N proteins) into Phase II and two S-only constructs into Phase I/II study in 2021. “Vaxart also provided data obtained from the Phase I study where T cell responses were compared to data from volunteers vaccinated with the Moderna or Pfizer mRNA vaccine distributed under emergency use authorizations. Our vaccine’s immune response appears very different than that seen from the leading injectables: mucosal antibodies rather than serum antibodies, and more potent T-cell responses,” said Andrei Floroiu, Vaxart’s CEO. “For our first oral COVID-19 vaccine candidate, we believe that these differences in immunogenicity profile may have a benefit in cross-reactive protection.”

Vaxart announced on August 2, 2021, the U.S. FDA had cleared an Investigational New Drug application for an S-only oral tablet SARS-CoV-2 vaccine candidate. “This is great news because it allows us to move forward with our first S-only vaccine construct,” said Andrei Floroiu, Vaxart’s CEO. “As we said at the end of the first quarter, we will explore multiple S-only constructs in clinical trials alongside the S+N construct that has already completed its Phase I trial. Together, the S-only and S+N constructs are part of our unique oral tablet COVID-19 vaccine candidate portfolio, which we believe could make a significant contribution to the fight against COVID-19 globally.”

Vaxart is primarily focused on developing oral recombinant protein vaccines based on its proprietary oral vaccine platform. This development effort is based on the oral vaccine platform, VAAST, which employs a modular approach using a replication-incompetent adenovirus type 5 (Ad5) vector that delivers two payloads to the cells of the mucosal epithelium of the small bowel. One payload is the gene coding for the selected pathogen-specific protein antigen. The other payload, which is always co-delivered, is the gene coding for the Toll-Like Receptor-3 (TLR-3) agonist, an adjuvant that activates the innate immune system and is selected for its ability to stimulate broad immune responses. Every vaccine contains the TLR-3 adjuvant component—reviews of Vaxart’s approach to tablet vaccine delivery.

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