Clinical Trial Info

Phase 2a Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Safety, Immunogenicity, and Efficacy of Bris10 M2SR (H3N2 A/Brisbane/10/2007) Vaccine Administered as a Single Intranasal Dose in Healthy Adults

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This Phase 2 study is to assess the effect of vaccination with Bris10/2007 M2SR (H3N2) vaccine on influenza viral shedding after intranasal challenge with a drifted H3N2 virus, A/Belgium/4217/2015.

Assess the safety of the Bris10 M2SR (H3N2) vaccine during the period from study vaccine administration until influenza virus challenge.

In the challenge study, adults 18-55 years of age were randomized to receive a single intranasal spray, either with placebo or with a 108 TCID50 dose of monovalent H3N2 M2SR vaccine. Four weeks later they were challenged with an influenza strain seven years drifted from the vaccine, a period during which WHO-recommended four H3N2 vaccine strain changes to maintain match against seasonal influenza virus.

Challenge study results demonstrated that, despite the significant mismatch of vaccine and challenge strains, a single dose of Bris2007 M2SR induced neutralizing antibody to the vaccine (48% of recipients) and challenge strain (27% of recipients). Overall, 54% of M2SR subjects were infected after the challenge, compared to 71% of placebo subjects. The subset of M2SR subjects with a vaccine-induced microneutralization response against the challenge virus had reduced rates of infection after challenge (38% vs. 71% of placebo subjects, P=0.0505) and reduced illness.

Results

The Journal of Infectious Diseases published on July 29, 2021 results of the Phase 2 clinical trial.

Results: Adverse events following vaccination were mild and similar in frequency between placebo and M2SR recipients. A single dose of Bris2007 M2SR induced neutralizing antibody to the vaccine (48% of recipients) and challenge strain (27% of recipients). Overall, 54% of M2SR subjects were infected after challenge, compared to 71% of placebo subjects. The subset of M2SR subjects with a vaccine-induced microneutralization response against the challenge virus had reduced rates of infection after challenge (38% vs. 71% of placebo subjects, P=0.0505) and reduced illness.

Conclusions: Subjects with vaccine-induced neutralizing antibodies were protected against infection and illness following a challenge with an antigenically distinct virus. This is the first demonstration of vaccine-induced protection against a highly drifted H3N2 challenge virus.