Is It Possible to Develop a "Universal" Influenza Virus Vaccine? Potential for a Universal Influenza Vaccine

Abstract

Development of optimal vaccines for influenza is challenging, in part as a result of the high antigenic variability in field strains associated with genetic shift from reassortment and genetic drift from point mutations. Discovery of conserved antigenic sites on the hemagglutinin (HA) protein for neutralizing antibodies suggested the possibility that influenza vaccines could be developed that induce focused antibody responses to the conserved neutralizing determinants, especially the HA stem region. Recent studies have focused on the antigenicity and immunogenicity of such domains, using monoclonal antibodies and candidate-engineered HA stem-based vaccines. Much progress has been made, but we still do not fully understand the biology of the immune response to this unique antigenic region.

Figure 1.

Structure of the influenza hemagglutinin (HA), with major domains. The structure shown is based on x-ray crystallographic studies of the trimeric soluble 1918 H1N1 influenza HA protein (PDB ID: 1RUZ). The structure contains a globular head domain that is the target for antibodies that bind to the receptor-binding domain and, rarely, the vestigial esterase domain. The stem region is more conserved and binds different classes of antibodies. General characteristics and inhibitory mechanisms of domain-specific human monoclonal antibodies are indicated.