Vaccine-induced V1V2-specific antibodies control and or protect against infection with HIV, SIV and SHIV

Abstract

Purpose of review: In humans, only one independent immunologic correlate of reduced risk of HIV infection has been identified: a robust antibody (Ab) response to the V1V2 domain of the gp120 envelope (Env) protein. In recent years, the presence and level of V1V2-specific Abs has also been correlated with protection from SIV and SHIV infections. Here, we review the multitude of studies showing the in-vivo protective effects of V1V2 Abs and review their immunologic characteristics and antiviral functions.

Recent findings: Structural and immunologic studies have defined four epitope families in the V1V2 domain: one epitope family, V2q, which preferentially presents as a quaternary structure of the Env trimer, and another epitope family (V2qt) which requires the quaternary trimeric Env structure; these two epitope types are recognized by two families of monoclonal Abs (mAbs)-V2q-specific and V2qt-specific mAbs-which display broad and potent neutralizing activity. A third epitope family, V2i, is present as a discontinuous conformational structure that overlays the α4β7 integrin binding motif, and a fourth epitope family (V2p) exists on V2 peptides. Antibodies specific for V2i and V2p epitopes display only poor neutralizing activity but effectively mediate other antiviral activities and have been correlated with control of and/or protection from HIV, SIV and SHIV. Notably, V2q and V2qt Abs have not been induced by any vaccines, but V2p and V2i Abs have been readily induced with various vaccines in nonhuman primates and humans.

Summary: The correlation of vaccine-induced V2p and V2i Abs with protection from HIV, SIV and SHIV suggests that these Ab types are extremely important to induce with prophylactic vaccines.

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FIGURE 1

Diagram of the position of the four epitope classes in the V1V2 region (V2p, V2i, V2q and V2qt), and examples of mAbs that target each of these epitopes.

FIGURE 2

Luminex reactivity of V2p mAb 8490 (a) and V2i mAb 697-30D (b) vs. cyclic V2 peptide (column 1), V1V2-tags (columns 2–4), V1V2-gp70 fusion proteins (columns 5–8), C5 peptide (column 9) and BSA (column 10).

FIGURE 3

Level of binding of mAbs to native-like Env. Results shown are for binding of mAbs to tetherin^hi Jurkat cells nucleofected with an mCherry+ NL4-3 reporter construct as described by Alvarez et al.[70]. Monoclonal Abs used (and the epitope for which they are specific) include: human antiparvovirus mAb (1418), A32 (anti-C1), b12 (CD4bs), 240 and 246 (gp41, cluster I), 447-52D (V3 crown), 697-30D (V2i), 830A (V2i), 2158 (V2i) and 10-1074 (V3-glycan).