To design vaccines with the capacity to elicit broadly neutralizing and/or immune protective features, it is essential to understand the requirements for relevant biological targeting specificity. In particular, for antibodies, not only the locale but the affinity, chemical contacts, steric constraints and physical insertion/extraction feature requirements at membranes must be elucidated. In this context, antibodies directed against the HIV-1 membrane proximal external region (MPER) will be used as examples. Explanation as to why only a subset of crossblocking mAbs are able to neutralize then becomes apparent. Likewise, in the case of CTL, fine details of both HLA and peptide specificities are required. With 4,269 different HLA allelic variants (-A, -B and -C) and divergence of fine specificity even within an HLA supertype, four-digit HLA typing is essential. In conjunction with definitive detection methodologies (i.e. Poisson detection MS3) capable of assessing virally infected and/or transformed cells for HLA arrayed peptides, CTL vaccines targeting conserved HLA-restricted epitopes become possible. Physical detection rather than reverse immunology assessment avoids pitfalls of incorrectly choosing targets as a consequence of irrelevant crossreactivity or, alternatively, misguiding crosspresentation. Here, examples from HPV-16 disease in humans relevant to HIV-1 infection are offered.
(C) 2013 Lippincott Williams & Wilkins, Inc.