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Oral Flu Vaccine Well-Tolerated and Immunogenic

January 30, 2020

By Will Boggs MD

NEW YORK (Reuters Health) - The VXA-A1.1 oral influenza vaccine was well tolerated and provided protective immunity against virus shedding similar to that of intramuscular inactivated influenza vaccine (IIV), in a phase II trial.

"An oral influenza vaccine would make a big impact on public health," Dr. Sean N. Tucker of Vaxart, in South San Francisco, California, told Reuters Health by email. "It's really easy to hand out tablets, and larger consumer purchases of a flu vaccine would reduce emergency room visits, hospitalizations, and even death. An improved needle-based vaccine wouldn't change the influenza market because consumers would have the same experience."

VXA-A1.1, a replication-defective adenovirus type-5 vectored vaccine, expresses the influenza hemagglutinin along with a novel toll-like receptor 3 agonist as an adjuvant. It is administered orally in tablets designed to release the virus in the ileum, a location previously shown to result in maximal immunogenicity in humans.

In an earlier phase I study, the vaccine was well-tolerated in healthy adults and stimulated substantial serum antibody responses.

In the current study, including 179 randomized participants ages 18 to 49, Dr. Tucker and colleagues assessed the protective efficacy of oral VXA-A1.1 versus intramuscular IIV and placebo in a well characterized human experimental infection model with the A/California/09 pH1N1 challenge virus 90 days or more after vaccination.

The frequency of influenza-positive illness after viral challenge, the primary efficacy endpoint, was nonsignificantly lower in the oral influenza vaccine (29%) and IIV (35%) groups than in the placebo group (48%), the team reports in The Lancet Infectious Diseases.

Despite similar efficacy of the two vaccines, the hemagglutination inhibition (HAI) geometric mean titers were significantly lower in the oral vaccine group (31.4) than in the intramuscular IIV group (186.7).

"The most surprising result to me was that the mechanism of protection was so different," Dr. Tucker said. "We did not see nearly as strong of a hemagglutination antibody response as the injected vaccine, and our most important correlate was making a generic hemagglutinin specific B cell with IgA and mucosal homing markers on the surface of those B cells."

"Because we got a statistically equivalent protection rate against illness, these results suggest that a mucosal response can be more efficient or more potent for influenza protection than a serum response," he said.

In the immunization phase, the most prevalent adverse events were headache in the oral vaccine and placebo groups and injection-site tenderness in the IIV group. There were no severe local or systemic reactions associated with immunization, and there were no serious adverse events or adverse events of special interest during the vaccination or challenge phases.

"From a seasonal influenza perspective, additional strains must be incorporated into the pill and tested such that oral vaccine can provide similar coverage as the current injected vaccines," Dr. Tucker said. "We have tested a quadrivalent influenza vaccine in ferrets, but have not tested in humans. This is the next step."

He added, "There are several key features of the technology, such as, it doesn't rely on egg production or needles. In a pandemic, these are likely to be in short supply and would likely be rate limiting for getting a vaccine out to the general population. The oral vaccine technology relies on growing the vaccine in cells, not eggs. Lastly, the technology that serves as the basis for this influenza vaccine is not influenza specific. It can be adapted with simple molecular biology to address other infectious diseases."

"The study provides promising data that could lead to an improved strategy for influenza immunization," write Dr. Larisa Rudenko and Dr. Irina Isakova-Sivak of the Institute of Experimental Medicine, in St. Petersburg, Russia, in a linked editorial. "Although the non-replicating adenovirus type-5 viral-vectored vaccine platform is feasible for use against a single pandemic influenza strain, more work is needed before this vaccine can be licensed for seasonal use."

This work might include comprehensive clinical and epidemiological studies of quadrivalent formulations, as well as studies supporting safety in young children for whom adjuvanted vaccines are not licensed in most countries, they note.

SOURCE: and Lancet Infectious Diseases, online January 21, 2020.

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