Universal Influenza A Vaccine Fails To Meet Efficacy in Phase 2 Trial

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Data from Australia show a T-cell antigen-inducing vaccine was unable to provide greater prevention of flu incidence than a placebo.

A universal influenza A vaccine failed to provide improved incidence of moderated T-cell response in an intention-to-treat population from a phase 2b trial assessing the candidate for tolerability, safety and efficacy.

The new findings, presented by Vaccitech-sponsored investigators including Dr. Thomas G. Evans, indicate the need to consider different regimen or administration strategy for the would-be universal vaccine.

Evans and colleagues assessed the recombinant viral-vectored vaccine—modified vaccinia Ankara expressing virus nucleoprotein and matrix protein 1 (MVA-NP+M1)—as a potential candidate capable of inducing responses to conserved CD4 and CD8 T-cell antigens, an added factor of immunization relevant to standard to influenza vaccination.

Their randomized, double-blind, placebo-controlled trial continued assessments of MVA-NP+M1—a product which previous assessments indicate would have substantial benefit in preventing universal influenza A viruses. In 8 outpatient clinical trial sites across Australia over 2 consecutive flu seasons, the vaccine showed capability to induce both CD4 and CD8 T-cells.

“In animal, epidemiological, and human challenge studies, a pre-existing T-cell response to internal proteins of influenza A has been associated with improved virological and disease outcomes,” they wrote.

Investigators randomly allocated 2152 Australian adults 1:1 to receive either MVA-NP+M1 (n = 1077) or placebo (n = 1075) from April 2 to June 14, 2019, to comprise the trial’s ITT analysis set. Participants were followed through the country’s flu season of May 1 to October 15 of that year. Just 1 in 5 (n = 419) participants were ≥65 years old.

There were little to no differences in laboratory-confirmed influenza incidence between participants receiving the universal vaccine (n = 35 [3.25%; 95% CI, 2.31 – 4.44]) and placebo (n = 23 [2.14%; 95% CI, 1.39 – 3.14]).The team observed 23 severe solicited local injection site reactions among 13 (0.6%) participants; 22 reactions were reported among participants receiving MVA-NP+M1. Another 100 severe systemic events were observed in 45 vaccine recipients, versus 20 in 14 placebo recipients. Additionally, 21 serious adverse events were reported among 18 MVA-NP+M1 recipients, versus 25 in 22 placebo recipients—but none were considered vaccine-related.

Investigators concluded the trial after the 1 Australia flu season due to futility and recommendation of the trial’s data monitoring committee.

While efficacy outcomes were lacking in the phase 2 assessment, investigators noted the would-be universal influenza A vaccine did provide good tolerability and no vaccine-associated serious adverse events.

“A vaccine designed to induce moderate T-cell responses to the cross-reactive internal proteins of influenza A did not lead to improved incidence when given within 28 days after standard QIV immunization,” they wrote. “A greater magnitude of T-cell response with a different vaccine or regimen, or localization in the lungs via alternative delivery, such as intranasal or aerosol, might be successful and require further investigation.”

The study, “Efficacy and safety of a universal influenza A vaccine (MVA-NP+M1) in adults when given after seasonal quadrivalent influenza vaccine immunisation (FLU009): a phase 2b, randomised, double-blind trial,” was published online in The Lancet Infectious Diseases.