New Early Trial Data Emerges From the First Oral COVID-19 Vaccine Candidate in the U.S.

Although many COVID-19 vaccines in use or in development have checked the box of stimulating the body to produce high levels of neutralizing antibodies, Sean Tucker, PhD, chief scientific officer of Vaxart points to a slew of other, potentially protective, immune responses that its candidate was found to elicit in newly released preliminary data.

In a presentation at a New York Academy of Sciences seminar, The Quest for a COVID-19 Vaccine, Tucker elaborated on the robust T-cell responses and mucosal antibodies against viral proteins (found in nasal swabs) that researchers saw among the 35 participants in its phase 1 trial. At the same time, “we did not see any neutralizing antibodies whatsoever [in the blood serum of these participants],” Tucker explained to the Academy audience. Many experts think that neutralizing antibodies play an important role in the protective immune response against SARS-Cov-2.

The phase 1 study found that trial volunteers had sharp upticks in a type of T-cell response known as CD8+, which is known to be important for long-lasting immunity against the spike protein (S) of the virus between day 1 and day 8 after they received the pill-based vaccine. In addition to S, Vaxart’s vaccine contains a viral protein called nucleocapsid (N), included, in part, to provoke T-cell responses. “These are some of the strongest [T-cell driven] immune responses…that we’ve ever seen,” Tucker noted.

Although T-cells have received less attention for the role they play in preventing COVID-19 disease and viral spread, Tucker enumerated the many potential ways that this arm of the acquired immune system may be important. Data have shown that T cells can reduce the severity and length of infection.

Nevertheless, Vaxart is not discounting the importance of the antibody response. In the phase 1 trial, 52% of the participants had mucosal, IgA antibodies that were specific to viral S and N proteins in nasal swab samples. The company is currently examining whether these IgA antibodies may be neutralizing against SARS CoV-2. Even if there are no detectable neutralizing antibodies against the virus in the blood, Tucker said, “it’s been documented that secretory [nasal] IgA is about 15 times more neutralizing than sera, so even low levels might be able to provide some meaningful results.”

Vaxart is now planning to do a phase 1 or phase 2 study this quarter to test a range of doses of its oral COVID-19 vaccine candidate to see if these can generate higher antibody responses. As Tucker noted, the doses already tested have been well tolerated in people and did not lead to any concerning side effects. Following this study, the company will plan a phase 2 or 3 efficacy trial, most likely in countries where vaccines are not available.

The Vaxart candidate stands out because it is one of the few in development that includes viral N. Tucker said there is probably less potential for virus variants to emerge with mutations in this protein, and as a result, there would be less potential for vaccine-resistant variants.

Additionally, since the vaccine is in pill form, it would be much easier to distribute. “Handing [vaccines] out is 20 to 30 times faster than giving them a shot,” Tucker noted, adding that vaccines Vaxart has developed using this technology are stable at room temperature for several years.