Dimeric 2G12 as a potent protection against HIV-1

We previously showed that broadly neutralizing anti-hiv-1 antibody 2g12 (human igg1) naturally forms dimers that are more potent than monomeric 2g12 in in vitro neutralization of various strains of hiv-1. in this study,we have investigated the protective effects of monomeric versus dimeric 2g12 against hiv-1 infection in vivo using a humanized mouse model. our results showed that passively transferred,purified 2g12 dimer is more potent than 2g12 monomer at preventing cd4 t cell loss and suppressing the increase of viral load following hiv-1 infection of humanized mice. using humanized mice bearing igg ''backpack'' tumors that provided 2g12 antibodies continuously,we found that a sustained dimer concentration of 5-25 mg/ml during the course of infection provides effective protection against hiv-1. importantly,2g12 dimer at this concentration does not favor mutations of the hiv-1 envelope that would cause the virus to completely escape 2g12 neutralization. we have therefore identified dimeric 2g12 as a potent prophylactic reagent against hiv-1 in vivo,which could be used as part of an antibody cocktail to prevent hiv-1 infection.© 2010 luo et al.