Which Antibody Functions are Important for an HIV Vaccine?

Abstract

HIV antibody (Ab) functions capable of preventing mucosal cell-free or cell-to-cell HIV transmission are critical for the development of effective prophylactic and therapeutic vaccines. In addition to CD4+ T cells, other potential HIV-target cell types including antigen-presenting cells (APCs) (dendritic cells, macrophages) residing at mucosal sites are infected. Moreover, the interactions between APCs and HIV lead to HIV cell-to-cell transmission. Recently discovered broadly neutralizing antibodies (NAbs) are able to neutralize a broad spectrum of HIV strains, inhibit cell-to-cell transfer, and efficiently protect from infection in the experimentally challenged macaque model. However, the 31% protection observed in the RV144 vaccine trial in the absence of detectable NAbs in blood samples pointed to the possible role of additional Ab inhibitory functions. Increasing evidence suggests that IgG Fcγ receptor (FcγR)-mediated inhibition of Abs present at the mucosal site may play a role in protection against HIV mucosal transmission. Moreover, mucosal IgA Abs may be determinant in protection against HIV sexual transmission. Therefore, defining Ab inhibitory functions that could lead to protection is critical for further HIV vaccine design. Here, we review different inhibitory properties of HIV-specific Abs and discuss their potential role in protection against HIV sexual transmission.

Evaluation of humoral, mucosal, and cellular immune responses following co-immunization of HIV-1 Gag and Env proteins expressed by Newcastle disease virus

“…[1][2][3] While the interest in NAb is clear, it should be stressed that RV144 was the only vaccine efficacy trial showing protection against HIV acquisition with little NAb activity but with new patterns of non-NAbs that may block transmission. [4][5][6] Similarly, V2 antibodies seem important for protection against SIV and SHIV challenges. 7 Although this study did not measure non-NAbs, in particular V1 and V2 identified as inversely correlated with risk of acquisition in RV144, this issue should be noted as deserving further studies.…”

Cocrystal Structures of Antibody N60-i3 and Antibody JR4 in Complex with gp120 Define More Cluster A Epitopes Involved in Effective Antibody-Dependent Effector Function against HIV-1

“…Their contribution to protection may result from a variety of antiviral mechanisms, including direct neutralization of virus and Fc receptor-dependent effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) or antibody-mediated phagocytosis (1)(2)(3)(4). Antibodies that directly neutralize HIV can provide protection, as evidenced in several nonhuman primate studies with passively transferred monoclonal antibodies (MAbs) (5)(6)(7)(8), although their role in preventing natural HIV transmission remains equivocal (reviewed in reference 9).…”

Progress in HIV vaccine development

“…59 Therefore, though only weakly neutralizing, Ab induced by RV144 may potentially mediate protection through aggregating or immobilizing virions in mucin layers, impeding transverse through mucosal barriers, [60][61][62] via IgG Fcg receptor (FcgR) dependent ADCVI including ADCC, [55][56][57] ADCP, 56,57 Ab-mediated release of cytokines or chemokines and complement-mediated killing. [50][51][52]59,63,64 ( Fig. 1).…”