Abstract
The HIV/AIDS pandemic is one of the most devastating pandemics worldwide. Today, the major route of infection by HIV is sexual transmission. One of the most promising strategies for vaccination against HIV sexual infection is the development of a mucosal vaccine, which should be able to induce strong local and systemic protective immunity. It is believed that both humoral and cellular immune responses are needed for inducing a sterilizing protection against HIV. Recently, passive administration of monoclonal neutralizing antibodies in macaques infected by vaginal challenge demonstrated a crucial role of FcγRs in the protection afforded by these antibodies. This questioned about the role of innate and adaptive immune functions, including ADCC, ADCVI, phagocytosis of opsonized HIV particles and the production of inflammatory cytokines and chemokines, in the mechanism of HIV inhibition in vivo. Other monoclonal antibodies - non-neutralizing inhibitory antibodies - which recognize immunogenic epitopes, have been shown to display potent FcγRs-dependent inhibition of HIV replication in vitro. The potential role of these antibodies in protection against sexual transmission of HIV and their biological relevance for the development of an HIV vaccine therefore need to be determined. This review highlights the potential role of FcγRs-mediated innate and adaptive immune functions in the mechanism of HIV protection.
Highlights
One estimates at more than 40 million the number of people living with HIV/AIDS in the world
The antigen-specific IgG specialize in the recognition of pathogenic agents, including HIV-1, and trigger various immune functions, such as neutralization, aggregation, phagocytosis, degranulation, cellular cytotoxicity (ADCC), virus inhibition (ADCVI or antibody-dependent cell-mediated virus inhibition) and the release of pro-inflammatory cytokines or chemokines
The induction of protective mucosal immunity is an important goal of future HIV vaccine design
Summary
One estimates at more than 40 million the number of people living with HIV/AIDS in the world. By preventing the infection of the first target cells of the virus such as immature dendritic cells and resident macrophages, localized in the vaginal mucosa (epithelium and submucosal sites), constitute a first line of defense against the virus at this portal of entry These key cells of the anti-infectious immunity are described to be permissive to HIV in vitro, being infected in vivo and producing de novo viral particles [1,2,3,4]. Antibodies that differ from neutralizing antibodies, referred to as unconventional antiviral or non-neutralizing inhibitory antibodies (reviewed in [20]) have been described to play a potent role in the inhibition of HIV replication in these APCs [21,22,23] These antibodies could represent new additional antibodies to induce by vaccinal immunization. Certain aspects concerning HIV inhibition by antibodies such as neutralization and Fc -mediated inhibitory activity will be discuss, and consequences for the development of new vaccination strategies will be highlighted
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