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Vaccines provide the most cost effective defense against pathogens. Although vaccines have been designed for a number of viral diseases, a vaccine against HIV-1 still remains elusive. In contrast, while there are excellent influenza vaccines, these need to be changed every few years because of antigenic drift and shift. The recent discovery of a large number of broadly neutralizing antibodies (bNAbs) and structural characterization of the conserved epitopes targeted by them presents an opportunity for structure based HIV-1 and influenza A vaccine design. We discuss strategies to design immunogens either targeting a particular antigenic region or focusing on native structure stabilization. This article is part of a Special Issue entitled: Recent advances in molecular engineering of antibody.