Hessell AJ, Shapiro MB, Powell R, et al. Reduced cell-associated DNA and improved viral control in macaques following passive transfer of a single anti-V2 monoclonal antibody and repeated SHIV challenges. present as a discontinuous conformational structure that overlays the 47 integrin binding motif, and a fourth epitope family (V2p) exists on V2 peptides. Antibodies specific for V2i and V2p epitopes Limaprost 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 Limaprost vaccines in nonhuman primates and humans. Summary The correlation of vaccine-induced V2p Limaprost and V2i Abs with protection from HIV, SIV and SHIV suggests that these Ab types are extremely important to induce with prophylactic vaccines. Keywords: antibodies, antiviral functions, epitope, nonhuman primates, V2, vaccines INTRODUCTION The key to the rational design of an effective HIV vaccine depends on the identification of immune correlates of protection and immunologic mechanisms that prevent HIV acquisition. The first independent correlate of reduced risk of HIV infection in humans was identified by studies of participants in the RV144 clinical vaccine trial: a robust antibody (Ab) response to the V1V2 region of the virus gp120 envelope (Env) glycoprotein. Similar correlations were subsequently identified in studies of nonhuman primates (NHPs) between protection Limaprost from SIV and SHIV and V2 Ab levels. Here, we summarize these human and NHP findings and the V2 Abs that are involved in the control of and/or protection from HIV, SIV and SHIV.? Open in a separate window Box 1 no caption available STRUCTURAL AND IMMUNOLOGIC CHARACTERIZATION OF THE V1V2 DOMAIN Studies of polyclonal sera from HIV-infected individuals have established that, over time, infection generates different humoral fingerprints [1]. This is true for patterns of Ab specificities, subclasses and antiviral activities [2C5,6?]. Similar findings pertain to Abs induced by vaccines targeting SIV [7?,8] and SHIV [9C12]. Given the association between V2 Abs and protection in human and animal models, it is critical to understand the complexity of the V1V2 domain of the virus Env and the Ab response to it. Conformational complexity of V1V2 In HIV, the V1V2 domain, like the rest of gp120, exhibits marked conformational flexibility. The V1V2 domain serves as the trimer association domain at the apex of the closed trimeric Env, but the V1V2 domain of each of the three gp120 protomers opens out when gp120 interacts with CD4 [13C15,16?]. The C-strand of V2, composed of amino acids (AAs) 170C176, one of the five strands composing the V1V2 -barrel, exists in different Limaprost conformations, varying between a -strand and an -helix [17C19], where the -strand configuration is preferentially present in the closed, structurally constrained trimeric Env, whereas the -helical conformation is preferred where there is less structural constraint when the Env is fully open. The preferred configuration is undoubtedly affected by the sequence of V1 and V2, substitutions at key residues, the molecular context in which the V1V2 domain is placed and the intraprotomer and interprotomer interactions of V1V2 within the Env trimer [20]. Alternative V2 conformational epitopes As a result of this configurational complexity, there are at least four types of epitopes in the V1V2 region as shown in Fig. ?Fig.1:1: V2q epitopes which preferentially recognize structures formed by the quaternary interaction of the three gp120 protomers and are glycan-dependent; V2q Rabbit Polyclonal to ACAD10 is recognized by V2q mAbs such as PG9 and PG16 [17,21C24]; V2qt epitopes which recognize quaternary, trimer-dependent V2 epitopes at the apical center of Env are recognized by several V2qt mAbs exemplified by PGT145 [25]; V2i epitopes which overlay the 47 integrin binding site in V2 and are recognized by V2i mAbs such as 830A and 2158 [26C28]; and V2p epitopes.