Oral Vaccination for Influenza Is Protective

By Brian Hoyle

SAN FRANCISCO -- October 9, 2018 -- An oral vaccine to a prevalent influenza strain is protective and induces a mucosal immune response at least as good as a commercial injectable quadrivalent influenza vaccine, according to a study presented here at ID Week 2018, the 56th Annual Meeting of the Infectious Diseases Society of America (IDSA).

Nikita Kolhatkar, PhD, Vaxart, Inc., San Francisco, California, presented the phase 2 trial (NCT02918006) on October 6.

The investigators compared the effectiveness of the oral recombinant adenovirus-based vaccine expressing hemagglutinin from A/California 04/09 with a commercial injectable quadrivalent influenza vaccine. The vaccine tablets were made with standard recombinant techniques rather than in eggs.

The study took place during 2016 and 2017. A total of 150 adult participants were randomised to receive the oral tablet vaccine and an intramuscular injection of placebo (n = 60). Injection of the quadrivalent influenza vaccine and a placebo tablet (n = 60), or placebo injection and tablet (n = 30).

Ninety to 120 days later, wild-type influenza A H1 virus was applied intranasally, and the development of flu was monitored according to changes in hemagglutinin titres, microneutralisation, and IgA/IgG antibody-secreting cell assays. Immunogenicity, including markers of activation and mucosal homing on B cells, was explored in preliminary analyses.

Nearly half (48%) of patients immunised with the oral vaccine tablet versus 38% of those immunised with the quadrivalent vaccine were protected against the virus. Furthermore, 37% of those who received the oral vaccine versus 44% of those who were immunised with the injectable vaccine and 71% of those who received placebo developed influenza.

Seroconversion occurred with 35% of those receiving the oral tablet vaccine and 83% of those receiving the quadrivalent vaccine. The lower rate of seroconversion with the oral formulation indicated that the mechanism of protection was not only associated with hemagglutinin inhibition.

Both vaccines induced a humoral immune response. However, the exploratory flow cytometry and sequencing analyses indicated the greater prevalence of activated plasmablasts expressing surface mucosal homing markers and a more diverse B cell population in the participants who received the oral vaccine versus those receiving the quadrivalent vaccine.

Overall, the oral influenza tablet protected against infection just as well as, and perhaps better than, the quadrivalent vaccine. The mechanism of protection may depend on the route of immunisation. This needs further exploration.

“The oral vaccine platform allows for homing of influenza-specific B cells to sites of infection, which may provide more effective mechanisms of protection. The oral delivery of an influenza vaccine can generate a robust, tissue-specific protective response comparable to intramuscular influenza vaccination,” concluded the researchers.

If the results pan out in the phase 3 trial, they would provide the means of formulating influenza vaccines that are effective and can be conveniently stored at room temperature.

Funding for the study was provided by the United States Department of Health and Human Services.
[Presentation title: Influenza Vaccination via Oral Tablet Is Protective and Induces a Unique Mucosal Immune Response. Abstract 1947]
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