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


METHODS
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.


CONCLUSIONS
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.
Université François-Rabelais - Inserm U966.
Martine
M
Braibant
Eun-Yeung
EY
Gong
Jean-Christophe
JC
Plantier
Thierry
T
Moreau
Elodie
E
Alessandri
François
F
Simon
Francis
F
Barin
D057134:Antibodies, Neutralizing / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000145:classification / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D008962:Models, Theoretical; D009500:Neutralization Tests / Q000379:methods
D057134:Antibodies, Neutralizing; D000939:Epitopes; D015483:HIV Antibodies