Abstract
The field of HIV research relies heavily on non-human primates, particularly the members of the macaque genus, as models for the evaluation of candidate vaccines and monoclonal antibodies. A growing body of research suggests that successful protection of humans will not solely rely on the neutralization activity of an antibody's antigen binding fragment. Rather, immunological effector functions prompted by the interaction of the immunoglobulin G constant region and its cognate Fc receptors help contribute to favorable outcomes. Inherent differences in the sequences, expression, and activities of human and non-human primate antibody receptors and immunoglobulins have the potential to produce disparate results in the observations made in studies conducted in differing species. Having a more complete understanding of these differences, however, should permit the more fluent translation of observations between model organisms and the clinic. Here we present a guide to such translations that encompasses not only what is presently known regarding the affinity of the receptor-ligand interactions but also the influence of expression patterns and allelic variation, with a focus on insights gained from use of this model in HIV vaccines and passive antibody therapy and treatment.
Highlights
Advances in the treatment and prevention of HIV have relied heavily on the macaque animal model
This review summarizes the current understanding of what differences exist in the setting of receptor and antibody interactions between humans and non-human primates, with a particular emphasis on those facets that have the potential to affect the evaluation of candidate vaccines and antibody-based strategies for the prevention or treatment of HIV-1 infection in humans
Relevant to the potential for differences between macaque and human FcγRII to drive differences in outcomes of antibody infusions between species, it is clear from evaluation of the binding profiles of engineered IgG sequence variants across human and rhesus receptors, that greater phenotypic differences are observed for FcγRII as compared to FcγRIII between species [153]
Summary
Advances in the treatment and prevention of HIV have relied heavily on the macaque animal model. The differences in the sequences, ligand binding affinities, and expression patterns of human and macaque IgG and IgG receptors raise the possibility that a potent effector functiondriven immune response may have a different phenotypic character in each species.
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