A New Strategy to Elicit Broadly Protective Antibodies to Influenza Viruses

Dr. Yoshihiro Kawaoka of the University of Tokyo in Japan will develop broadly effective influenza vaccines by mixing together epitopes of conserved fragments of the viral hemagglutinin (HA) protein, which only elicit a weak immune response, together with millions of different, non-naturally occurring fragments that elicit a strong immune response, to induce broadly cross-reacting antibodies. Influenza is of world-wide concern severely impacting public health and the global economy. Tens of millions of reported cases result in tens of thousands of deaths annually in the U.S. alone, and the rapid spread of the virus between countries causes epidemic or pandemic outbreaks. Traditional vaccines are directed towards selected epitopes in the head region of the viral HA protein because they elicit a strong immune response. However, these regions are frequently mutated, rendering the vaccines useless. Vaccines directed towards more conserved epitopes only elicit a weak immune response, but this can be strengthened using HA proteins previously unseen by the immune system. They will produce a library of millions of HA epitopes that contain artificial mutations in the immune-dominant regions while preserving the conserved regions. This should focus the production of highly reactive antibodies against the conserved HA epitopes, which will eliminate a wider range of influenza strains. They will test this using single and repeat immunizations of different mixes in ferrets. Once optimized, the vaccination strategy will be tested in ferrets pre-exposed to influenza virus to mimic the human situation. The result will be a single vaccination that protects against a wider range of influenza strains than traditional vaccines.