Oral Influenza Vaccine Shows Promise in Phase 2 Study

Early seasonal estimates for the 2019-20 influenza indicate that there have been more than 13 million cases of the flu reported in the United States so far.

Officials with the US Centers for Disease Control and Prevention are encouraging all Americans to receive a flu shot, as vaccination is the best way to reduce the risk of influenza and any associated complications.

Although flu vaccine effectiveness estimates are not available yet for this influenza season, authors of a new article in The Lancet Infectious Diseases are calling out the need for new vaccines with alternative administration methods to improve the efficacy of the flu shot.

The authors of the report were the investigators on a phase 2 trial of an oral influenza vaccine candidate, VXA-A1.1, which was evaluated in a human influenza challenge model.

In a phase 1 trial conducted in 2015 the oral vaccine candidate demonstrated favorable safety and immunogenicity results. The phase 2 study was a single-site, placebo-controlled, and active-controlled investigation that was conducted in California.

The study enrolled 179 healthy individuals between the ages of 18-49 years who had an initial A/California/H1N1 hemagglutination inhibition of less than 20.

The primary outcomes were safety, which was assessed in all immunized participants through 365 days, and influenza-positive illness after viral challenge.

Study participants were randomly assigned 2:2:1 to receive a single immunization of either 10¹¹ infectious units of VXA-A1.1 orally, a full human dose of quadrivalent inactivated influenza vaccine via intramuscular injection, or matched placebo. In total, 71 individuals were placed in the oral vaccine group, 72 in the quadrivalent group, and 36 in the placebo group.

Individuals receiving the vaccine and all staff were masked to group assignments.

Ninety days after the immunization, individuals without clinically significant symptoms or signs of influenza—a temperature higher than 38.9° Celsius, a positive result for respiratory viral shedding on a Biofire test, and any investigator-assessed contraindications—were challenged intranasally with 0.5mL wild-type A/CA/like(H1N1)pdm09 influenza virus.

In total 143 individuals were eligible for challenge, 58 in the oral vaccine group, 54 in the quadrivalent group and 31 in the placebo group. After challenge, influenza-positive illness was detected in 29% (17 of 58) in the oral vaccine group, 35% (19 of 54) in the quadrivalent group, and 48% (15 of 31) in the placebo group.

The investigators report that the study vaccine was well tolerated and that no serious or significant adverse events were recorded. The most prevalent solicited events were headache in the oral vaccine group (7%) and placebo group (19%) and tenderness at injection site in the quadrivalent group (26%).

“Orally administered VXA-A1.1 was well tolerated and generated protective immunity against virus shedding, similar to a licensed intramuscular IIV,” the investigators concluded. “These results represent a major step forward in developing a safe and effective oral influenza vaccine.”