Toward Effective Vaccines for Avian Influenza

Although world attention is focused on Ebola, concern persists over future influenza pandemics caused by the novel avian influenza A H7N9 and H5N1 strains recently found in Asia. The development of effective vaccines against these strains would be of great benefit, but progress has been limited by relatively low immunogenicity. Two groups report new strategies to enhance the effectiveness of such vaccines.

In a randomized, controlled trial involving 700 adults, Mulligan and colleagues assessed the safety and efficacy of various doses of a split virus inactivated monovalent H7N9 vaccine preparation — with or without the oil-in-water MF59 adjuvant — administered intramuscularly on days 0 and 21. Although almost no participants had seroconverted by day 21, even when given doses containing 45 μg of hemagglutinin, those who received any adjuvanted priming dose from 3.75 to 15 μg of hemagglutinin had high seroconversion rates 21 days after the second dose. Both older age and receipt of seasonal influenza vaccine in the 2012–2013 or 2013­­–2014 season were associated with lower seroconversion rates. Adjuvant use was associated with a higher likelihood of local reactions.

In a similar controlled trial, Belshe and colleagues studied the safety and efficacy of various doses of a monovalent inactivated surface antigen H5N1 influenza vaccine, with or without the MF59 adjuvant. A total of 565 vaccine-naive adults received immunizations on days 0 and 28; in addition, 72 individuals who had received one or two doses of an older H5N1 influenza vaccine 1 year earlier received a single dose of the new vaccine. By day 28 after immunization, 21% to 50% of the previously vaccinated participants had high hemagglutinin inhibition assay antibody titers, regardless of adjuvant use; the neutralizing antibody response was similarly high. Two doses of the older vaccine seemed to offer no advantage over a single dose. In the vaccine-naive population, there was no significant response to a single immunization, but a demonstrable dose response occurred following the second, with or without adjuvant use. In all groups, the antibody response lasted <180 days. The vaccine was generally well tolerated, but among participants who received adjuvanted vaccine, systemic events (primarily mild malaise) were more common in those who had previously been immunized.