Envelope-Specific Recognition Patterns of HIV Vaccine-Induced IgG Antibodies Are Linked to Immunogen Structure and Sequence

Conclusions: IgG recognition of linear antigenic Env regions differed between the two trials particularly after the second MVA boost. Structural features of the MVA-encoded immunogens, such as secreted, monomeric gp120 vs. membrane-anchored, functional gp150, and differences in prime-boost immunogen sequence variability most probably contributed to these differences. Prime-boosting with multivalent Env immunogens during TMV01 did not improve variant cross-recognition of immunodominant peptide variants in the V3 region. Introduction Development of an efficacious vaccine against the Human Immunodeficiency Virus-1 (HIV) is complicated by high variability of the HIV envelope glycoprotein (Env), and by the difficulty to induce broadly cross-reactive neutralizing HIV Env-specific antibody responses (1, 2). Vaccine-induced protection from HIV acquisition may nonetheless be possible in the absence of a strong HIV neutralizing antibody response; during the Rv144 trial, high IgG levels targeting the Env hypervariable regions 1 and 2 (V1V2) correlated with protection from HIV acquisition (3). Subsequent studies further mapped this V1V2-specific IgG response to a linear 15 mer peptide in the V2 region located in close proximity to the α4β7 integrin-binding motif (4, 5). IgG responses against linear peptides covering the highly immunogenic V3 region were also inversely correlated with infection risk in Rv144 in a subgroup analysis (4), whereas recognition of other,...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research