title: Antibodies to conserved epitopes of the HIV-1 envelope in sera from long-term non-progressors: prevalence and association with neutralizing activity.
abstract: 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 microg/ml [interquartile range (IQR), 2.7-9.3 microg/ml] versus 2.3 microg/ml (IQR, 1.1-3.9 microg/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.
  
  
  CONCLUSIONS
  These results suggest that the antigenicity of the "silent face" of gp120 that exposes the 2G12 epitope should be analysed in more detail, to find ways to induce broadly neutralizing antibodies.
authors.affiliation: Laboratoire de Virologie, Université François-Rabelais, INSERM ERI 19, 37044 Tours cedex, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Braibant
authors.forename: Sylvie
authors.initials: S
authors.lastname: Brunet
authors.forename: Dominique
authors.initials: D
authors.lastname: Costagliola
authors.forename: Christine
authors.initials: C
authors.lastname: Rouzioux
authors.forename: Henri
authors.initials: H
authors.lastname: Agut
authors.forename: Hermann
authors.initials: H
authors.lastname: Katinger
authors.forename: Brigitte
authors.initials: B
authors.lastname: Autran
authors.forename: Francis
authors.initials: F
authors.lastname: Barin
mesh_terms: D000918:Antibody Specificity; D000937:Antigen-Antibody Reactions; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D015483:HIV Antibodies / Q000097:blood*; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015700:HIV Envelope Protein gp41 / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology*; D009500:Neutralization Tests; D018709:Statistics, Nonparametric
chemical_list: D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D016056:Immunodominant Epitopes