MF59 Adjuvant Enhances Diversity and Affinity of Antibody-Mediated Immune Response to Pandemic Influenza Vaccines

Adjuvant use improves the quality and quantity of the immune response to pandemic influenza vaccines. A Shot in the Arm for the Flu Vaccine Because flu vaccine production begins months before the flu season, vaccine producers and world health officials have to guess which strains will predominate in a coming year. Although they’re frequently right, sometimes a dark horse arises that wasn’t predicted, and vaccine makers have to play catch-up. Speed is of the essence when attempting to prevent a pandemic, and limited supplies could hinder a worldwide vaccination campaign, preventing the broad coverage that protects even unvaccinated people. Khurana et al. report that the use of an oil-in-water adjuvant, MF59, improves the magnitude, robustness, and strength of the immune response to pandemic flu vaccines and may decrease the amount of antigen required for each dose. The authors looked at the quantitative and qualitative effects of MF59 on the antibody response in patients from various age groups who were vaccinated with the swine-origin H1N1 flu vaccine. They found that in adults and children who had been either previously vaccinated or exposed to the flu, MF59 increased the diversity and volume of neutralizing antibody responses to the flu vaccine. Antibody responses were slightly different in toddlers, suggesting that there may be distinct requirements for activating primary and recall antibody responses. MF59 also increased the strength with which these antibodies bound to the flu virus. These results support the use of adjuvants with flu vaccinations. Such a strategy could help expand coverage and decrease morbidity in the event of pandemic influenza and give vaccine makers the edge in a game of catch-up with dark horses. Oil-in-water adjuvants have been shown to improve immune responses against pandemic influenza vaccines as well as reduce the effective vaccine dose, increasing the number of doses available to meet global vaccine demand. Here, we use genome fragment phage display libraries and surface plasmon resonance to elucidate the effects of MF59 on the quantity, diversity, specificity, and affinity maturation of human antibody responses to the swine-origin H1N1 vaccine in different age groups. In adults and children, MF59 selectively enhanced antibody responses to the hemagglutinin 1 (HA1) globular head relative to the more conserved HA2 domain in terms of increased antibody titers as well as a more diverse antibody epitope repertoire. Antibody affinity, as inferred by greatly diminished (≥10-fold) off-rate constants, was significantly increased in toddlers and children who received the MF59-adjuvanted vaccine. Moreover, MF59 also improved antibody affinity maturation after each sequential vaccination against avian H5N1 in adults. For both pandemic influenza vaccines, there was a close correlation between serum antibody affinity and virus-neutralizing capacity. Thus, MF59 quantitatively and qualitatively enhances functional antibody responses to HA-based vaccines by improving both epitope breadth and binding affinity, demonstrating the added value of such adjuvants for influenza vaccines.