Bob Roehr

May 05, 2010

May 5, 2010 (Bethesda, Maryland) — Coadministration of a fusion protein with trivalent influenza vaccine (TIV) might increase titers of protective antibody by 50%, according to preliminary research presented here at the National Foundation for Infectious Diseases 13th Annual Conference on Vaccine Research.

Current vaccines are less effective at generating high titers of antibody in older people, noted presenter H. Keipp Talbot, MD, from Vanderbilt University Medical Center in Nashville, Tennessee.

Dr. Talbot garnered the Maurice R. Hilleman Early-Stage Career Investigator Award, which includes $10,000 in research support, for research he and his colleagues conducted on an enhanced influenza vaccine.

VAX102 is a novel vaccine that fuses the M2e membrane protein, conserved across influenza, to a toll-like receptor (TLR)5 ligand, in this case Salmonella typhimurium flagellin.

The goal is to heighten antibody titers and to broaden their response so that they provide some cross-protection to variants of influenza not included in the TIV, Dr. Talbot explained. In animal models, it protects against influenza challenge and enhances response to standard TIV.

The multicenter double-blind, randomized controlled phase 1 trial involved 80 participants 18 to 49 years of age. They received either TIV plus placebo or TIV plus VAX102.

End points were day 14 and day 28 hemagglutination inhibition (HI) titers, and M2e and flagellin as assessed by ELISA. The study was powered to evaluate safety and reactive immunogenicity, but not to reach conclusions about efficacy.

Dr. Talbot said the vaccinations were well tolerated, with modest increased injection-site pain associated with VAX102, but no serious adverse events. The VAX102 group did generate higher levels of response (approximately 1.5 times higher) to H1 and H3 than placebo, but the difference did not reach statistical significance.

David S. Fedson, MD, retired medical director of Aventis Pasteur MSD, called the study intriguing but very preliminary. One important and still-unanswered question is whether the response generated has any cross-reactive effect on virus not included in the TIV.

In a subsequent conversation with Medscape Infectious Diseases, Dr. Talbot said that the US Food and Drug Admnistration (FDA) uses HI antibody titers of 1:40 or higher for the purposes of licensure. "We know what that means in young healthy adults. We're not sure what that means in older adults. We don't know what immune response means you're protected."

She pointed out that chronological age alone is not an absolute predictor of response. "There is a frailty factor, as well. Your immune age may be older than your chronologic age."

The study only measured titers at postvaccination days 14 and 28, mileposts used by the FDA. It did not evaluate titers at a later time point to see if the fusion protein affected the persistence of antibody titers, nor has it evaluated the efficiency or functionality of the antibody generated in both groups.

The study was funded by Vanderbilt University and VaxInnate Corp., a privately held company developing TLR-oriented seasonal influenza vaccines. The researchers have disclosed no relevant financial relationships.

National Foundation for Infectious Diseases (NFID) 13th Annual Conference on Vaccine Research: Abstract P10. Presented April 27, 2010

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