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Review
. 2019 Apr;16(2):169-179.
doi: 10.1007/s11904-019-00432-x.

The Antibodiome-Mapping the Humoral Immune Response to HIV

Audrey L Butler  1 , Stephanie Fischinger  1 , Galit Alter  2
Affiliations
Review

The Antibodiome-Mapping the Humoral Immune Response to HIV

Audrey L Butler et al. Curr HIV/AIDS Rep. 2019 Apr.

Abstract

Purpose of review: The design of an HIV vaccine remains an elusive but top priority. Data from the non-human primate model and the first moderately protective HIV vaccine trial (RV144) point to a role for qualitative changes in humoral immune functions in protection from infection. Here, we review the current understanding of the antibody response throughout HIV infection, the known correlates of protection, and current strategies to manipulate antibodies to put an end to the epidemic.

Recent findings: Recent studies point to innate immune-recruiting antibody function in preventing infection as well as controlling viremia following infection. These data have begun to inform next-generation design of HIV vaccines and antibody therapies by uncovering new viral targets and antibody architectures to improve potency and breadth. Emerging data illustrate a role for innate immune recruiting-antibodies in conferring protection against HIV infection as well as promoting viral control and clearance, offering an unprecedented opportunity to modulate and improve antibody function to fight HIV more effectively.

Keywords: Antibodies; HIV-1; Innate immunity; Natural HIV control; Vaccination.

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Conflict of interest statement

Conflict of Interest

The authors declare that they have no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Figures

Fig. 1
Fig. 1
Humoral immunity timeline in HIV. During the first weeks of acute infection, HIV envelope-specific IgM and IgG antibodies are produced sequentially to a number of epitopes (gp41, gp120, V3 loop, CD binding site, and MPER) and are non-neutralizing but capable of inducing Fc-mediated functions, such as antibody-dependent cellular cytotoxicity (ADCC) by natural killer (NK) cells. The first neutralizing antibody responses appear after months of infection and are specific to autologous viral strains. Over the following years, some individuals spontaneously control infection. These individuals harbor innate immune-recruiting antibodies. Broadly neutralizing antibody responses, conversely, evolve largely in individuals who fail to control infection
Fig. 2
Fig. 2
Known correlates of protection and viral control. Polyfunctional HIV-specific antibody responses (able to recruit multiple innate immune effector cell populations), higher HIV-specific IgG3 antibodies, unique HIV-specific antibody glycan profiles, and elevated ADCC activity are enriched in both spontaneous controllers and in animals or humans protected from infection. Controllers also exhibit elevated levels of p24-specific antibodies. Additionally, protected vaccinated humans and NHPs harbor elevated V1V2-specific antibodies and antibodies able to drive antibody-dependent cellular phagocytosis (ADCP). Finally, while not enriched in naturally protected individuals, the administration of broadly neutralizing antibodies (bNAbs) can confer protection against infection. Thus, many shared, but some unique humoral profiles, are associated with protection from infection and control of viremia
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