Oral Influenza Tablet Vaccine Protects Against Infection, Induces Unique Immune Response

Investigators have found that an oral tablet for influenza vaccination can protect against infection just as well as—if not better than—a commercial injectable quadrivalent influenza vaccine.

Results from the phase 2 trial were presented at the 2018 Annual ID Week Meeting in San Francisco, CA, this week by investigators from Vaxart, Inc, the clinical-stage biotechnology company that developed the tablet, which was manufactured using standard recombinant techniques rather than in eggs.

“According to recent studies, the common practice of growing influenza vaccine in chicken eggs can render the flu vaccine less effective in humans,” David Liebowitz, MD, said in a recent statement. “Our vaccines are not vulnerable to this issue.”

For the phase 2 clinical challenge trial, the investigators compared the effectiveness of the oral recombinant adenovirus-based vaccine expressing hemagglutinin (HA) from A/California 04/09 with a commercial injectable quadrivalent influenza vaccine (QIV).

From 2016 to 2017, participants between the ages of 19 and 49 were randomized into 3 treatment groups and were administered either the oral tablet vaccine and a placebo intramuscular injection, a QIV injection and a placebo tablet, or a double placebo.

Ninety to 120 days after they were immunized, participants were challenged intranasally with wildtype influenza A H1 virus to determine vaccine efficacy and durability.

Investigators measured changes in HAI titers, microneutralization, and IgA/IgG ASC assays. Exploratory flow cytometry assessed quantitative and qualitative aspects of immunogenicity, including markers of activation and mucosal homing on B cells, poster authors write.

Analyses were performed on days 0 and 7 after participants were immunized and 0 and 6 days after they were virally challenged. Investigators then isolated plasmablasts sorted from peripheral blood mononuclear cells (PBMCs) for genomic DNA and sequenced them for heavy chain receptor sequencing through the use of next-generation sequencing analysis.

A total of 48% of the participants who were immunized with the oral vaccine tablet were protected against the virus, according to the investigators, whereas only 38% of those immunized with the QIV were protected.

Furthermore, 37% of those who were given the oral tablet vaccine went on to develop influenza infection compared with 44% of those who were immunized with QIV and 71% of those who received placebo.

Both vaccines were noted to have induced a humoral immune response; however, NGS and FACs analyses indicated that those who received the oral tablet had more activated plasmablasts expressing surface mucosal homing markers and a more diverse B cell population than those who received QIV.

Overall, the oral influenza tablet protected against infection just as well as the QIV, if not better, but the mechanism of protection may be unique to the route of immunization, the investigators postulate.

“Oral immunization allows for specific homing of influenza-specific B cells to sites of infection and produces a more diverse antibody repertoire,” they concluded.

Disclosures:

N. Kolhatkar, Vaxart, Inc.: Employee, Salary; K. Gottlieb, Vaxart, Inc.: Employee, Salary; K. Kasparek, Vaxart, Inc.: Employee, Salary; K. Hodgson, Vaxart, Inc.: Employee, Salary; S. Tucker, Vaxart, Inc: Employee, Salary; D. Liebowitz, Vaxart, Inc.: Employee and Investigator, Salary.

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