Neutralizing Antibody Response and Antibody-Dependent Cellular Cytotoxicity in HIV-1–Infected Individuals from Guinea-Bissau and Denmark

Abstract

The development of therapeutic and prophylactic HIV vaccines for African countries is urgently needed, but the question of what immunogens to use needs to be answered. One approach is to include HIV envelope immunogens derived from HIV-positive individuals from a geographically concentrated epidemic with more limited viral genetic diversity for a region-based vaccine. To address if there is a basis for a regional selected antibody vaccine, we have screened two regionally separate cohorts from Guinea-Bissau and Denmark for neutralizing antibody activity and antibody-dependent cellular cytotoxicity (ADCC) against local and nonlocal circulating HIV-1 strains. The neutralizing activity did not demonstrate higher potential against local circulating strains according to geography and subtype determination, but the plasma from Danish individuals demonstrated significantly higher inhibitory activity than that from Guinea-Bissau individuals against both local and nonlocal virus strains. Interestingly, an opposite pattern was observed with ADCC activity, where Guinea-Bissau individual plasma demonstrated higher activity than Danish plasma and was specifically against the local circulating subtype. Thus, on basis of samples from these two cohorts, no local-specific neutralizing activity was detected, but a local ADCC response was identified in the Guinea-Bissau samples, suggesting potential use of regional immunogens for an ADCC-inducing vaccine.

Evolution of Antibody Responses in HIV-1 CRF01_AE Acute Infection: Founder Envelope V1V2 Impacts the Timing and Magnitude of Autologous Neutralizing Antibodies

“…However, IgG levels or subclass did not associate with plasma ADCC activity, indicating that in part, different antibody populations may be mediating these two different plasma antibody functions. This discordance between plasma ADCC and neutralization has been previously demonstrated ( 15 , 77 , 78 ); this relationship may be affected by plasma potency, HIV-1 subtype, and target viral strain. Neutralizing antibodies have been shown to mediate ADCC activity ( 79 ), and ADCC-mediating non-neutralizing antibodies exist.…”

Selection of HIV Envelope Strains for Standardized Assessments of Vaccine-Elicited Antibody-Dependent Cellular Cytotoxicity-Mediating Antibodies

“…It is well established that neutralizing antibodies can mediate ADCC ( 21 , 27 ), and a previous study found, for monoclonal antibodies, that neutralization and ADCC were generally correlated ( 28 ). While this had not previously been found using sera from infected individuals ( 29 , 30 ), this may be due to the limited number of viruses used in these studies. We observed an overall positive but limited relationship between antibody neutralization and ADCC in our panel of sera, suggesting there is an overlap in neutralization and ADCC function of antibodies in polyclonal antibody responses.…”

Cross-Reactive Antibodies With the Capacity to Mediate HIV-1 Envelope Glycoprotein–Targeted Antibody-Dependent Cellular Cytotoxicity Identified in HIV-2–Infected Individuals

“…Thus, our results largely reproduce earlier results [7, 8] but also for the first time reveal that HIV-2 infection can trigger antibodies mediating ADCC against cells presenting other HIV-1 Env variants. Interestingly, the strongest HIV-1 cross-reactive ADCC was seen against targets coated with one of the Envs originating from CRF02_AG, an HIV-1 subtype frequently found in the area of the study participants and also suggested to influence the strength of intratype ADCC in HIV-1–infected populations in this region [14].…”