|Title||Epitope mapping of broadly neutralizing human HIV-2 monoclonal antibodies.|
|Publication Type||Journal Article|
|Year of Publication||2012|
|Authors||Kong, R, Li H, Georgiev I, Changela A, Bibollet-Ruche F, Decker JM, Rowland-Jones SL, Jaye A, Guan Y, Lewis GK, Langedijk JP, Hahn BH, Kwong PD, Robinson JE, Shaw GM|
|Journal||Journal of virology|
|Date Published||2012 Aug 29|
Recent studies have shown that natural infection by HIV-2 leads to the elicitation of high titers of broadly neutralizing antibodies (Nabs) against primary HIV-2 strains (J Virol 86:930-946, 2012; J Virol 86:947-960, 2012; J Virol 86:961-971, 2012). Here we describe the envelope (Env) binding and neutralization properties of 15 anti-HIV-2 human monoclonal antibodies (mAbs), 14 of which were newly generated from 9 chronically-infected subjects. All 15 mAbs bound specifically to HIV-2 gp120 monomers and neutralized heterologous primary virus strains HIV-2(7312A) and HIV-2(ST). Ten of 15 mAbs neutralized a third heterologous primary virus strain HIV-2(UC1). Median IC(50) neutralization concentrations for these mAbs were surprisingly low, ranging from 0.007 to 0.028 μg/ml. Competitive Env binding studies revealed three mAb competition groups: CG-I, CG-II and CG-III. Using peptide scanning, site-directed mutagenesis, chimeric Env constructions and single-cycle virus neutralization assays, we mapped the epitope of CG-I antibodies to a linear region in variable loop 3 (V3); the epitope of CG-II antibodies to a conformational region centered on the carboxy-terminus of V4; and the epitope(s) of CG-III antibodies to conformational regions associated with CD4- and coreceptor-binding sites. HIV-2 Env is thus highly immunogenic in vivo and elicits antibodies having diverse epitope specificities, high potency and wide breadth. In contrast to the HIV-1 Env trimer, which is generally well-shielded from antibody binding and neutralization, HIV-2 is surprisingly vulnerable to broadly reactive Nabs. The availability of 15 human mAbs targeting diverse HIV-2 Env epitopes can facilitate comparative studies of HIV/SIV Env structure, function, antigenicity and immunogenicity.
|Short Title||J Virol|