In the Journals

Low-dose H7N9 vaccine with adjuvant produced greatest seroconversion

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November 5, 2014

Point-of-use mixing and administration of influenza A(H7N9) vaccine with MF59 adjuvant produced the highest rate of seroconversion at the lowest tested dose, according to recent data.

Mark J. Mulligan, MD, of the Hope Clinic of the Emory Vaccine Center, and colleagues examined the safety and immunogenicity of different influenza A(H7N9) vaccine doses mixed with or without the MF59 adjuvant through a randomized, double blind trial. Seven hundred adults, aged 19 to 64 years, were randomly assigned into seven groups. The vaccine was administered intramuscularly on days 0 and 21 of the trial, with doses and presence of the MF59 adjuvant varying with each group.

Antibody levels were screened at 42 days, with a successful seroconversion defined as a titer of 40 or greater as measured by hemagglutination inhibition assay, or a neutralizing antibody titer increasing fourfold to a level of 40 or greater. Other measured outcomes included serious adverse vaccine-related events through month 13, and solicited post-vaccination symptoms through day 7.

Hemagglutination inhibition antibodies were at their highest after administration of the adjuvant-mixed vaccine at a dose of 3.75 mcg. At 42 days, seroconversion occurred in 59% (95% CI, 48%-68%) of this group, with a mean titer of 33 (95% CI, 24.7-44.1). Seroconversion within this group peaked at 29 days, with 62% (95% CI, 52%-72%) of participants achieving the main outcome measure. Higher antigen doses were not associated with increased levels.

Neutralizing antibody assay results also peaked for the 3.75-mcg dose. At 42 days, seroconversion occurred in 82% (95% CI, 73%-89%), with a mean titer of 81.4 (95% CI, 66.6-99.5).

Both antibody levels were low among participants given the vaccine without adjuvant, while higher doses of vaccine with adjuvant were not associated with increased antibody levels. No difference was seen in hemagglutination inhibition seroconversion after mixing adjuvant with either the first (35%; 95% CI, 25%-45%) or both (47%; 95% CI, 37%-58%) vaccine doses at 15 mcg.

Recent reception of the seasonal influenza vaccine and older age were linked with diminished seroconversion. No serious adverse events related to the vaccine occurred. Solicited post-vaccination symptoms were generally mild, with more local symptoms seen in groups administered the adjuvant.

“The significant antigen dose-sparing effect of MF59 is an important finding, potentially allowing for protection of many more people with limited vaccine,” the researchers wrote. “The study did not determine the optimal antigen dose to combine with MF59 because the lowest dose produced the maximum antibody seroconversion. This is an area for future research.”

Disclosure: Mulligan reported receiving a personal fee for serving on a data and safety monitoring committee for VaxInnate.

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