Antibody Cross-Reactivity to Hemagglutinin Protein Antigens Demonstrates Feasibility for Development of a “universal” Influenza A Synthetic Peptide Vaccine

Influenza A viruses spread rapidly, causing widespread seasonal epidemics of respiratory disease worldwide, which results in more than a billion cases and 500,000 deaths annually [1]. Current influenza vaccines primarily elicit antibodies against the receptor-binding region of the head domain of the hemagglutinin (HA) glycoprotein trimer (Figure 1). This region is hyper-variable and highly mutable, leading to new forms of the virus that can evade neutralizing antibodies. The stem region of HA contains highly conserved α-helical sequences as a result of their functional role in membrane fusion and virus entry. Studies have shown that a few rare neutralizing human monoclonal antibodies can recognize these highly conserved epitopes and neutralize both homotypic and heterotypic influenza strains [2,3]. There are some 18 HA subtypes in influenza A virus that infect humans, animals and birds (Figure 1) [4].