Quadrivalent nasal flu vaccine performed well against nasal trivalent vaccine

BOSTON — No significant differences in immunologic response and tolerability were observed between a quadrivalent nasal influenza vaccine and the currently licensed nasal trivalent vaccine, according to findings presented here at the 50th Interscience Conference on Antimicrobial Agents and Chemotherapy.

Currently approved influenza vaccines contain the A/H1N1, A/H3N2 and one B strain, according to Stan L. Block, MD, professor of clinical pediatrics at the University of Kentucky, who presented the results.

Block said the lineage of the usual B strains — Yamagata and Victoria — are antigenically dissimilar lineages and have been co-circulating in an unpredictable manner from year to year. A new nasal quadrivalent vaccine containing both B strains could have an increased protective effect.

“In recent years, influenza B is averaging about 25% of total circulating influenza strains,” Block said. “Predicting which B strain will be dominant has been like a flip of the coin. As a result, the B lineage has been mismatched in 5 of the last 8 years, and that translates into poor vaccine efficacy.”

The quadrivalent vaccine is an investigational four-strain formulation from MedImmune, which contains two A strains and two B strains, with one B strain coming from each B lineage. Block said the vaccine is manufactured in the same process as the licensed vaccine, in that it is cold-adapted, attenuated and temperature-sensitive. These similarities permit bridging of efficacy and safety data of quadrivalent vaccine to the currently available trivalent vaccine.

“A new quadrivalent formulation of vaccine may be the wave of the future for flu vaccines,” he said. “In the next 5 years, we are going to see a switch over to a quadrivalent version of vaccine for both the nasal and injectable flu vaccines.”

The current study, funded by MedImmune, compared the immunogenicity of the vaccines in 1,800 U.S. adults aged 18 to 49 years. The trial was conducted in March 2009.

Participants were randomly assigned in a 4:1:1 fashion to receive one dose of the quadrivalent vaccine or matched trivalent vaccine containing a B Victoria or B Yamagata strain.

The primary outcome measure was immunologic noninferiority of the quadrivalent vaccine to the trivalent vaccine. This was measured by observing whether the upper limits of 95% CIs for strain-specific geometric mean titer ratios of trivalent to quadrivalent vaccines after dosing were within the predetermined margin of 1.5 or less.

“A secondary outcome measured the proportion of recipients with post-dose hemagglutination inhibition titer that produced a fourfold rise in titer,” he said.

The endpoints of safety and tolerability included comparison of solicited symptoms gathered from diaries on days 0 to 14, adverse events from days 0 to 28 and serious adverse events on days 0 to 180.

Block reported positive results for the quadrivalent vaccine. “The four strains — influenza A/H1N1, A/H3N2, B/Yamagata and B/Victoria — were immunologically noninferior,” he said. “This is good news. There was no interference with an additional B strain in the vaccine.”

Secondary efficacy outcomes of seroconversion and seroresponse rates were also comparable. “Basically, we saw that the two groups had similar rises in antibody titers,” Block said.

No statistically significant differences were observed in the safety and tolerability profiles of the vaccines.

“The adverse events we observed were ones that are commonly reported and similar to what is expected from LAIV in the literature,” Block said. – by Rob Volansky

For more information:

Block S. G1-1343. Noninferior Immunologic Response of Quadrivalent, Live Attenuated Influenza Vaccine (Q/LAIV) Compared with Trivalent LAIV (T/LAIV). Presented at: 50th Interscience Conference on Antimicrobial Agents and Chemotherapy; Sept. 12-15, 2010; Boston.