Cross-group neutralization of HIV-1 and evidence for conservation of the PG9/PG16 epitopes within divergent groups

Abstract

Objective: HIV-1 has been classified into four groups: M, N, O and P. The aim of this study was to revisit the cross-group neutralization using a highly diverse panel of primary isolates.

Design: The panel of viruses included nine HIV-1 group O primary isolates, one recombinant M/O primary isolate, one group N primary isolates, one group P primary isolate, two group M (subtype B) primary isolates and the HIV-1 group M adapted strain MN.

Methods: All the viruses were tested for neutralization in TZM-bl cells, using sera issued from patients infected by viruses of group M (n = 11), O (n = 12) and P (n = 1), and a panel of nine human monoclonal broadly neutralizing antibodies (HuMo bNAbs).

Results: Although the primary isolates displayed a wide spectrum of sensitivity to neutralization by the human sera, cross-group neutralization was clearly observed. In contrast, the bNAbs did not show any cross-group neutralization, except PG9 and PG16. Interestingly, the group N prototype strain YBF30 was highly sensitive to neutralization by PG9 (IC50: 0.28 μg/ml) and PG16 (IC50: < 0.12 μg/ml). The interaction between PG9 and key residues of YBF30 was confirmed by molecular modeling.

Conclusion: The conservation of the PG9 and PG16 epitopes within groups M and N provides an argument for their relevance as components of a potentially efficient HIV vaccine immunogen.