Implications of broadly neutralizing antibodies in the development of a universal influenza vaccine

Abstract

Serum antibodies are the major correlate of influenza vaccine efficacy, providing short-term protection against infection. Recent efforts have been focused on studying antibody responses at a monoclonal level to understand their role in protection against influenza, and to ultimately improve vaccine strategies to provide broader, long-term immunity against influenza virus. These studies have shown that broadly neutralizing antibodies specific for the conserved stem domain of the hemagglutinin protein can target multiple strains of influenza. These antibodies show great promise both from a therapeutic perspective as well as for guiding vaccine design efforts. In this review, we will summarize past and recent findings about broadly neutralizing antibodies against influenza, and discuss how these findings may guide development of universal vaccine strategies.

Figure 1. Influenza virus and the HA protein

A) Influenza virus is a negative-sense, single stranded RNA virus with a genome consisting of 8 RNA segments, encoding for a total of 11 poteins. 3 proteins are expressed on the virus surface, including the HA protein (red and blue), NA protein (orange), and M protein (not pictured). B) The HA protein is made of an HA1 (binds to sialic acid receptor) and HA2 (mediates membrane fusion) segment, linked by a disulfide bond. C) The HA protein is expressed as a trimer on the virus surface. The HA1 domain encodes for the immunogenic head domain, which is highly variable between strains of influenza and prone to rapid mutation. The HA2 domain is more conserved between influenza strains and is rarely mutated.