Increasing the breadth and potency of response to the seasonal influenza virus vaccine by immune complex immunization

PNAS – Proceedings of the National Academy of Sciences of the United States
of America
[Accessed 9 September 2017]

Biological Sciences – Immunology and Inflammation:
Increasing the breadth and potency of response to the seasonal influenza virus vaccine by immune complex immunization
Jad Maamary, Taia T. Wang, Gene S. Tan, Peter Palese, and Jeffrey V. Ravetch
PNAS 2017 ; published ahead of print September 5, 2017, doi:10.1073/pnas.1707950114
Influenza viruses remain a source of substantial morbidity and mortality worldwide. This is, in part, because current approaches to vaccination elicit strain-specific immune responses. Here, we report a method for targeting the Fc receptor, CD23, during vaccination with existing influenza vaccines (TIV) to increase the breadth and potency of the antibody response. Immunization with the TIV in complex with a monoclonal antibody that is broadly reactive against the hemagglutinin glycoprotein and engineered at the Fc domain to engage CD23 elicited antibodies that were 10-fold increased in potency and that protected against the potential pandemic influenza virus subtype H5N1 in vivo. This work demonstrates that broadly protective influenza immunity can be achieved using existing seasonal vaccines.
The main barrier to reduction of morbidity caused by influenza is the absence of a vaccine that elicits broad protection against different virus strains. Studies in preclinical models of influenza virus infections have shown that antibodies alone are sufficient to provide broad protection against divergent virus strains in vivo. Here, we address the challenge of identifying an immunogen that can elicit potent, broadly protective, antiinfluenza antibodies by demonstrating that immune complexes composed of sialylated antihemagglutinin antibodies and seasonal inactivated flu vaccine (TIV) can elicit broadly protective antihemagglutinin antibodies. Further, we found that an Fc-modified, bispecific monoclonal antibody against conserved epitopes of the hemagglutinin can be combined with TIV to elicit broad protection, thus setting the stage for a universal influenza virus vaccine.