HIV-Specific B Cell Frequency Correlates with Neutralization Breadth in Patients Naturally Controlling HIV-Infection

HIV-specific broadly neutralizing antibodies (bnAbs) have been isolated from patients with high viremia but also from HIV controllers that repress HIV-1 replication. In these elite controllers (ECs), multiple parameters contribute to viral suppression, including genetic factors and immune responses. Defining the immune correlates associated with the generation of bnAbs may help in designing efficient immunotherapies. In this study, in ECs either positive or negative for the HLA-B*57 protective allele, in treated HIV-infected and HIV-negative individuals, we characterized memory B cell compartments and HIV-specific memory B cells responses using flow cytometry and ELISPOT. ECs preserved their memory B cell compartments and in contrast to treated patients, maintained detectable HIV-specific memory B cell responses. All ECs presented IgG1 + HIV-specific memory B cells but some individuals also preserved IgG2 + or IgG3 + responses. Importantly, we also analyzed the capacity of sera from ECs to neutralize a panel of HIV strains including transmitted/founder virus. 29% and 21% of HLA-B*57 + and HLA-B*57 − ECs, respectively, neutralized at least 40% of the viral strains tested. Remarkably, in HLA-B*57 + ECs the frequency of HIV-Env-specific memory B cells correlated positively with the neutralization breadth suggesting that preservation of HIV-specific memory B cells might contribute to the neutralizing responses in these patients.
Highlights • In contrast to treated HIV-infected patients, elite controllers (ECs) maintain HIV-specific memory B cell responses. • In HLA-B*57 + ECs, HIV-specific B cell frequency correlates positively with the neutralization breadth of tier-2 HIV strains. • In HLA-B*57 + and HLA-B*57 − ECs different antibody functions are probably involved in suppressing HIV replication. A fraction of HIV-1-infected individuals (so-called elite controllers, ECs) naturally control HIV-1 replication maintaining undetectable viral loads. Understanding the mechanisms implicated in natural control of HIV-1 infection will help in developing efficient HIV vaccines. In ECs, we analyzed the influence of B cell antibody responses. We show that in contrast to successfully treated HIV-1-infected patients, ECs preserve memory B cell compartments and maintain HIV-specific B cell responses. In ECs positive for the protective HLA-B*57 allele, HIV-specific memory B cell responses are positively associated with the breadth of HIV neutralization. These findings will help develop novel immunotherapies to fight HIV.