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PLoS One ; 10(6): e0128823, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26039641

RESUMEN

We recently reported the induction of potent, cross-clade neutralizing antibodies (nAbs) against Human Immunodeficiency Virus type-1 (HIV-1) in rabbits using gp120 based on an M-group consensus sequence. To better characterize these antibodies, 93 hybridomas were generated, which represent the largest panel of monoclonal antibodies (mAbs) ever generated from a vaccinated rabbit. The single most frequently recognized epitope of the isolated mAbs was at the very C-terminal end of the protein (APTKAKRRVVEREKR), followed by the V3 loop. A total of seven anti-V3 loop mAbs were isolated, two of which (10A3 and 10A37) exhibited neutralizing activity. In contrast to 10A3 and most other anti-V3 loop nAbs, 10A37 was atypical with its epitope positioned more towards the C-terminal half of the loop. To our knowledge, 10A37 is the most potent and broadly neutralizing anti-V3 loop mAb induced by vaccination. Interestingly, all seven anti-V3 loop mAbs competed with PGT121, suggesting a possibility that early induction of potent anti-V3 loop antibodies could prevent induction of more broadly neutralizing PGT121-like antibodies that target the conserved base of the V3 loop stem.


Asunto(s)
Anticuerpos Monoclonales/química , Anticuerpos Neutralizantes/química , Epítopos/química , Anticuerpos Anti-VIH/química , Proteína gp120 de Envoltorio del VIH/química , VIH-1/química , Secuencia de Aminoácidos , Animales , Anticuerpos Monoclonales/biosíntesis , Anticuerpos Monoclonales/aislamiento & purificación , Anticuerpos Neutralizantes/biosíntesis , Anticuerpos Neutralizantes/aislamiento & purificación , Sitios de Unión de Anticuerpos , Secuencia Conservada , Epítopos/inmunología , Femenino , Anticuerpos Anti-VIH/biosíntesis , Anticuerpos Anti-VIH/aislamiento & purificación , Proteína gp120 de Envoltorio del VIH/administración & dosificación , Proteína gp120 de Envoltorio del VIH/inmunología , VIH-1/inmunología , Hibridomas/inmunología , Modelos Moleculares , Datos de Secuencia Molecular , Pruebas de Neutralización , Unión Proteica , Estructura Secundaria de Proteína , Estructura Terciaria de Proteína , Conejos , Vacunación
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