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


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

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

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.

Related Videos
Getting Black Men Involved in Their Health Care, Clinical Research
Patient Involvement in Advanced HF Treatment, with Ashley Malliett, DMSc, MPAS, PA-C
Aaron Henry, PA-C, MSHS: Regaining Black Male Patient Trust in the Doctor's Office
Tailoring Chest Pain Diagnostics to Patients, with Kyle Fortman, PA-C, MBA
Solutions to Prevent Climate Change-Related Illness, with Janelle Bludhorn, PA-C
Kyle Fortman, PA-C, MBA: Troponin and Heart Injury Risk Screening Recommendations
What Should the American Academy of Physician Associates Focus on in 2025?
The Rising Rate of Heat-Related Illness, with Janelle Bludhorn, PA-C
© 2024 MJH Life Sciences

All rights reserved.