EBioMedicine (Jul 2017)

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

  • Angeline Rouers,
  • Jéromine Klingler,
  • Bin Su,
  • Assia Samri,
  • Géraldine Laumond,
  • Sophie Even,
  • Véronique Avettand-Fenoel,
  • Clemence Richetta,
  • Nicodème Paul,
  • Faroudy Boufassa,
  • Laurent Hocqueloux,
  • Hugo Mouquet,
  • Christine Rouzioux,
  • Olivier Lambotte,
  • Brigitte Autran,
  • Stéphanie Graff-Dubois,
  • Christiane Moog,
  • Arnaud Moris

DOI
https://doi.org/10.1016/j.ebiom.2017.05.029
Journal volume & issue
Vol. 21, no. C
pp. 158 – 169

Abstract

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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.

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