Antibodies to conserved epitopes of the HIV-1 envelope in sera from long-term non-progressors: prevalence and association with neutralizing activity

Objective: Previous studies have shown that broadly neutralizing antibodies (NAb) are more frequent in long-term non-progressors (LTNP) than in other HIV-1 infected patients, but nothing is known about the envelope regions targeted by these broadly NAb. We investigated whether the breadth of neutralizing activity of sera was associated with the presence of specific antibodies (2F5- and/or 4E10-like, b12-like or 2G12-like antibodies) directed against conserved epitopes known to be involved in broad neutralization. Methods: We assessed the ability of sera from 67 LTNP of the French ANRS cohort (ANRS CO15) to neutralize four heterologous primary isolates of four various clades. Competitive and non-competitive ELISA were developed for the specific comparison of levels of antibodies against these specific epitopes in neutralizing and non-neutralizing sera from LTNP. Results: We found that higher 2G12-like antibody levels were significantly associated with the broadest neutralizing activity in sera from LTNP. Levels of 2G12-like antibodies were higher in the sera that neutralized the four isolates than in the others, with a median of 5.7 mu g/ml [interquartile range (IQR), 2.7-9.3 mu g/ml] versus 2.3 mu g/ml (IQR, 1.1-3.9 mu g/ml) (Mann-Whitney test, P = 0.03). Levels of antibodies against the other targeted envelope epitopes did not differ significantly between broadly and non-broadly neutralizing sera. Conclusion: These results suggest that the antigenicity of the 'silent face' of gp120 that exposes the 2612 epitope should be analysed in more detail, to find ways to induce broadly neutralizing antibodies. (c) 2006 Lippincott Williams & Wilkins.