Reverse Vaccinology 2.0 Shows Great Promise Dennis R. Burton Department of Immunology and Microbial Science, Center for HIV/AIDS Vaccine Immunology and Immunogen Design, IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California 92037; and Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts 02129 Correspondence: burtonscripps.edu Abstract

Functional antibodies, i.e., those with antipathogen activity in in vitro assays, are generally the best correlate of vaccine protection. Mimics of natural infection, including live attenuated and killed pathogens, which induce such antibodies in vivo, have generated highly successful vaccines. However, pathogens that induce functional antibodies at lower levels or more sporadically have been more refractory to vaccine design. Such pathogens are being tackled by more systematic approaches involving identifying functional antibodies, templating immunogens from the antibodies, and then evaluating the immunogens iteratively. I believe this is a powerful new approach to vaccine design as discussed below.