Universal Flu Vaccine Safe, Immunogenic

By Marilynn Larkin

March 11, 2020

NEW YORK (Reuters Health) - A single dose of adjuvanted FLU-v may provide safe, long-lasting protection against a broad spectrum of influenza viruses, a phase 2b randomized controlled trial suggests.

FLU-v is a mix of four synthetic peptides designed to provide cross-protection against influenza A and B strains by inducing both humoral and cell-mediated immunity.

"We have recently completed two phase 2 studies - FLU-v 003, testing immunogenicity (the current study), and FLU-v 004, testing efficacy in a human challenge study," Dr. Olga Pleguezuelos of SEEK in London, UK, told Reuters Health by email. "The results show that a single dose of adjuvanted FLU-v induces cellular and antibody responses, and that it has a clinical impact in reducing disease, symptom and viral load."

"The advantages over the seasonal flu vaccine are that the composition of the FLU-v vaccine will remain the same year after year, and it is manufactured synthetically, enabling year-round manufacturing and thus, increasing the number of doses available worldwide," she explained. "It will not be subject to a strict vaccination window, as it is the case with seasonal flu vaccine. Also, ... it should provide protection against new strains of flu virus."

Further, she added, "The vaccine does not contain live or attenuated influenza virus and therefore it should be safe to administer to the elderly and the young."

As reported in Annals of Internal Medicine, Dr. Pleguezuelos and colleagues randomized 175 mostly white healthy adults (mean age, about 40; about 53% women overall) to 0.5 mL of the following formulations given subcutaneously on days 0 and 21: nonadjuvanted FLU-v; adjuvanted (with Montananide ISA-51) FLU-v; nonadjuvanted placebo; and adjuvanted placebo.

With respect to safety, injection site reactions were the most common mild-to-moderate adverse events.

With regard to immunogenicity, a median 38.2-fold increase in secreted interferon-gamma was seen at day 42, and a 25.0-fold increase at day 180, between adjuvanted FLU-v and adjuvanted placebo. Thus, the primary endpoint of enhancing T-cell responses was met, according to the authors, as interferon-gamma is one of the most important markers of T-cell mediate immunity against influenza infection.

At day 42, differences between adjuvanted FLU-v and adjuvanted placebo were a median 4.5-fold for IFN-gamma-producing CD4+ T cells; 4.9-fold for tumor necrosis factor-alpha; 7.0-fold for interleukin-2; and 1.7-fold for CD107a.

At day 180, differences were 2.1-fold for IFN-gamma and 5.7-fold for IL-2. No differences were seen for TNF-alpha or CD107a.

Further, overall, no differences in cell-mediated immunity were seen between non-adjuvanted FLU-v and non-adjuvanted-placebo.

Dr. Pleguezuelos said meetings are scheduled with regulatory authorities in the U.S. and Europe "to gain further insight into phase 3 preparation."

Dr. Daniel Kuritzkes, Chief, Division of Infectious Diseases at Brigham and Women's Hospital in Boston, commented in an email to Reuters Health, "The data from the study appear promising in terms of the ability of the novel vaccine to induce influenza-specific immune responses and in terms of overall safety. Whether it is appropriate to proceed to phase 3 efficacy trials depends on the results of the challenge study, alluded to at the end of the discussion (section of the paper) but apparently as yet unpublished."

"In theory, the vaccine could be broadly protective, because it is designed to induce immune responses against parts of the virus that are less variable than the targets of current flu vaccines," he said. "Whether the novel vaccine will truly protect against a broad spectrum of strains can only be determined in challenge studies and, ultimately, in phase 3 clinical trials."

"Issues that clinicians should have in mind include how will this vaccine compare to currently available flu vaccines; if protective, how durable will that protection be (e.g., will people need to get a booster each year?); and how many injections will be needed," he said. "This study gave two shots three weeks apart - it's hard enough getting people in to get a single flu shot, how realistic is it that they will return for a second vaccination? That might be acceptable if two shots gave lifelong protection, but is less desirable if good for only a single season."

"Lastly," he said, "larger studies are needed to determine safety in a broader population, including children and the elderly."

SOURCE: http://bit.ly/39DiGhK Annals of Internal Medicine, online March 9, 2020.