Point-of-use H7N9 vaccine shows promise

PHILADELPHIA — An inactivated virus against influenza A/Shanghai/2/13 (H7N9) demonstrated efficacy in 60% of healthy adults, according to findings presented here.

Mark J. Mulligan, MD, of the departments of medicine and infectious diseases at Emory University in Atlanta, and colleagues aimed to compare the safety and immunogenicity of the H7N9 vaccine with or without MF59 adjuvant.

The analysis included 700 healthy individuals aged 19 to 64 years. Participants were given the vaccine intramuscularly on days 0 and 21 at nominal antigen doses of 3.75 mcg, 7.5 mcg, 15 mcg, or 45 mcg.

Field site mixing of the antigen with the vaccine was performed for both, one or neither of the doses, according to the researchers.

Antibody titers on day 42 served as the primary outcome measure along with vaccine-related serious adverse events and solicited local and systemic symptoms after vaccination. The clinicians also performed assays of B and T cells on a subset of 37 patients.

Results indicated minimal hemagglutination inhibition and nominal antigen after two doses of unadjuvanted vaccine or one dose of the vaccine with any dose of the adjuvant.

For the 3.75 mcg dose plus the adjuvant, hemagglutination inhibition seroconversion — defined as a 4-fold titer rise to >40 — was reported in 60% (95% CI, 50-70) of patients. This dose also yielded a day-42 geometric mean titer of 35 (95% CI, 26-47), and a neutralizing antibody seroconversion rate of 84% (95% CI, 76-91) with a geometric mean titer of 85 (95% CI, 69-104).

The response did not increase with a higher dose of antigen.

Comparable results were reported for the adjuvant with the first of two 15-mcg doses and the two adjuvanted 15-mcg doses.

“It appears better to give the adjuvant with the first dose than with the second dose,” Mulligan said. “The antigen dose did not matter in groups with the adjuvant dose. There was not as much of a response with a single dose of adjuvant, but when you give that second dose, you can see a response.”

Understanding the dynamics of how the vaccine and the adjuvant work together could provide the clinical community the opportunity to administer both with maximum efficiency, thereby sparing resources, according to Mulligan.

Antibody responses were attenuated by seasonal influenza vaccination and aging. “The adjuvant partially overcomes preexisting immunity effect from seasonal vaccination,” he said. “Higher age was associated with less day-42 seroconversion.”

A correlation was observed between antibody responses and antibody-secreting B cells on day 8 (ASC; R=0.43; P=.01) and CD4+ICOS+CXC3+CXCR5+ T follicular helper cells (TFH; R=0.57; P<.001) in blood, but not with memory B cells on day 0.

Mulligan reported no vaccine-related severe adverse events.

“The study indicates potential value in this rapid response tactic against H7N9,” Mulligan said. “Remaining questions include antibody duration and protective efficacy.” — by Rob Volansky

For more information:

Mulligan MJ. Abstract LB-2. Presented at: IDWeek 2014. Oct. 8-12; Philadelphia.

Disclosure: Mulligan reports no relevant financial disclosures.