Abstract
Influenza virus, a highly mutable respiratory pathogen, causes significant disease nearly every year. Current vaccines are designed to protect against circulating influenza strains of a given season. However, mismatches between vaccine strains and circulating strains, as well as inferior vaccine effectiveness in immunodeficient populations, represent major obstacles. In an effort to expand the breadth of protection elicited by influenza vaccination, one of the major surface glycoproteins, hemagglutinin (HA), has been modified to develop immunogens that display conserved regions from multiple viruses or elicit a highly polyclonal antibody response to broaden protection. These approaches, which target either the head or the stalk domain of HA, or both domains, have shown promise in recent preclinical and clinical studies. Furthermore, the role of adjuvants in bolstering the robustness of the humoral response has been studied, and their effects on the vaccine-elicited antibody repertoire are currently being investigated. This review will discuss the progress made in the universal influenza vaccine field with respect to influenza A viruses from the perspectives of both antigen and adjuvant, with a focus on the elicitation of broadly neutralizing antibodies.
Highlights
Influenza virus is a major cause of respiratory disease, causing significant morbidity and mortality in the United States and across the globe
Mice were primed with the H4 subtype HA in a DNA vaccine, followed by two boosts with inactivated viruses expressing Chimeric HAs (cHAs) constructs, one with a mH10/3 HA, a mH14/3 HA, comprising antigenic sites A through E of either the H10 or the H14 subtype, respectively, and the remaining head and stem residues from the H3 subtype [68]. This approach elicited antibodies with Fc-mediated effector functions targeting the stem domain, in addition to neutralizing, head-directed antibodies [68]. These results suggest that the Mosaic HAs (mHAs) approach can elicit both effective anti-head antibodies like those produced by the current vaccine, as well as broader anti-stalk antibodies similar to those produced from chimeric and headless HAs
Headless HA designs have been refined greatly, preserving the natural conformation of native HAs and its associated epitopes. mHA vaccines appear to elicit antibodies against both the HA head and stem domains, potentially optimizing the antibody response to maintain a neutralizing and broadened epitope pool
Summary
Influenza virus is a major cause of respiratory disease, causing significant morbidity and mortality in the United States and across the globe. Influenza B viruses consist of virus strains of the Victoria and Yamagata lineages, which co-circulate and demonstrate plasticity in the HA and neuraminidase (NA) proteins due to immune pressure [5]. Vaccination is effective at reducing the incidence of influenza virus, but annual vaccination is required for inducing protection due to constant antigenic drift. In efforts to obviate the necessity for yearly vaccines, and to increase their effectiveness against circulating strains, several approaches towards ‘universal’ influenza vaccines, those that elicit an immune response against the majority of encountered influenza viruses, have been pursued. Given that adjuvants have been recognized as a key component of influenza vaccines by conferring a robust immune response, a number of adjuvants under study will be discussed
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