Host Factors Impact Vaccine Efficacy: Implications for Seasonal and Universal Influenza Vaccine Programs

Abstract

Influenza is a global public health problem. Current seasonal influenza vaccines have highly variable efficacy, and thus attempts to develop broadly protective universal influenza vaccines with durable protection are under way. While much attention is given to the virus-related factors contributing to inconsistent vaccine responses, host-associated factors are often neglected. Growing evidences suggest that host factors including age, biological sex, pregnancy, and immune history play important roles as modifiers of influenza virus vaccine efficacy. We hypothesize that host genetics, the hormonal milieu, and gut microbiota contribute to host-related differences in influenza virus vaccine efficacy. This review highlights the current insights and future perspectives into host-specific factors that impact influenza vaccine-induced immunity and protection. Consideration of the host factors that affect influenza vaccine-induced immunity might improve influenza vaccines by providing empirical evidence for optimizing or even personalizing vaccine type, dose, and use of adjuvants for current seasonal and future universal influenza vaccines.

Keywords: aging; microbiota; obesity; pandemic; pregnancy; seasonal influenza; sex difference.

FIG 1

Several host-associated factors can impact influenza vaccine efficacy (i.e., the ability of vaccine-induced immunity to protect against subsequent influenza virus infection). Studies of humans and nonhuman animals immunized with inactivated influenza vaccines (IIVs) suggest that biological sex and gender-associated factors (e.g., behavior), age, and immune history are predictors of IIV-induced humoral immunity (i.e., correlate of protection) and presumably protection against influenza. Evidence also suggests that the composition of the gut microbiota, obesity, and pregnancy can impact IIV-induced immunity in humans. With growing concerns about the efficacy of seasonal IIVs, there is a push for development and implementation of universal influenza vaccine platforms. The impact of host factors, in both preclinical and clinical studies, on vaccine-induced immunity should be considered in an effort to maximize immunity conferred by influenza vaccines, including universal influenza vaccines.