Despite the wide use of flu vaccines, influenza viruses are still a global public health concern. To date, seasonal influenza vaccines have had suboptimal real-world effectiveness due in part to rapid accumulation of viral mutations, mismatched strains, and low immunogenicity among vulnerable populations. Even when the vaccine matches currently circulating influenza strains, effectiveness has only reached about 60%. This limited effectiveness may indicate that the type of immune response elicited is also a key factor for immunizing a population. Dr. Xin Tong, the lead author on this study, along with researchers from Dr. Daniel Lingwood’s and Dr. Ted Ross’ labs in the Center for Influenza Vaccine Research for High-Risk Populations (CIVR-HRP) explored differences in the immune response elicited by two currently approved and globally utilized influenza vaccines.
The authors profiled the functional humoral immune response, immunity that is dependent on antibodies, of two well-known influenza vaccines. FluMist, a mucosal replication-competent live attenuated influenza vaccine (LAIV), utilizes a live weakened virus and is administered via nasal spray. Fluzone, an inactivated influenza vaccine (IIV), uses a viral particle that is unable to replicate and is administered via intramuscular injection. Tong et al. documented the antigen-specific antibody binding, antibody titers, and antibody-dependent cell functions of the vaccines against a panel of hemagglutinin and neuraminidase antigens, including currently circulating, historical, future, and computationally optimized broadly reactive antigens (COBRAs).
The authors found that differences in immune responses to the two vaccines came down to quality versus quantity. The IIV/Fluzone vaccine induced significantly higher antibody titers and binding, but lower overall functional activity. In contrast, the LAIV/FluMist vaccine produced fewer antibodies, but they were more effective at eliciting higher levels of natural killer (NK) cell activation and phagocytosis to specific target antigens. When comparing functionality per antibody, the LAIV/FluMist vaccine induced superior antibodies compared to IIV/Fluzone.
Future studies should disentangle whether the delivery site (intranasal versus intramuscular) or the makeup of the vaccine (live attenuated versus inactivated) plays a larger role in the quality of a flu vaccine. Despite this caveat, the authors stress that future vaccine development should consider qualitative differences among vaccine candidates instead of relying solely on quantitative measurements (antibody binding and titers) to guide vaccine candidate selection.
