Current influenza vaccines are unsatisfactory because they are only
protective against viral variants closely related to the immunizing
strain and require annual immunizations to account for the antigenic
drift of the circulating viruses. Development of strain- and
subtype-independent vaccines to influenza virus requires detailed
knowledge of conserved antibody epitopes that are shared between the
different strains and subtypes of influenza.
We aim at he development of novel vaccines targeting these conserved epitopes in influenza A hemagglutinin (HA) by pursuing three different research goals. First, monoclonal cross-subtype neutralizing antibodies will be isolated from healthy donors with broad neutralizing activity in their serum. The epitopes of these monoclonal antibodies will then be characterized on a molecular level. Second, it is planned to solve the crystal structure and effector mechanisms of different HA subtypes bound to known cross-subtype neutralizing monoclonal antibodies. Third, the knowledge gained from these projects will be used to formulate the epitopes of HA that can confer cross-subtype neutralization and to engineer and test immunogens that elicit protective antibodies directed against these domains.
Vaccine candidates arising from this project should not only be able to reduce the number of immunizations required to protect against currently circulating strains of influenza A but they may also provide partial or total protections against emerging avian Influenza strains with pandemic potential.