Efficient Neutralization of Primary Isolates of HIV-1 by a Recombinant Human Monoclonal Antibody

Abstract

The ability of antibodies to neutralize diverse primary isolates of human immunodeficiency virus-type 1 in vitro has been questioned, with implications for the likely efficacy of vaccines. A recombinant human antibody to envelope glycoprotein gp120 was generated and used to show that primary isolates are not refractory to antibody neutralization. The recombinant antibody neutralized more than 75 percent of the primary isolates tested at concentrations that could be achieved by passive immunization, for example, to interrupt maternal-fetal transmission of virus. The broad specificity and efficacy of the antibody implies the conservation of a structural feature on gp120, which could be important in vaccine design.

Identification and specificity of broadly neutralizing antibodies against HIV

“…The first HIV bnAbs were isolated by our laboratory using phage display12, 13, 14 and by Hermann Katinger's laboratory using human hybridoma electrofusion 15, 16. These were the bnAbs b12 and 2F5.…”

Immunogenicity of recombinant human immunodeficiency virus type 1-like particles expressing gp41 derivatives in a pre-fusion state

“…Nevertheless, rare potent monoclonal antibodies (mAbs) with broad neutralizing activity have been isolated from infected individuals. The two NAbs b12 and 2G12 are directed against exterior gp120 protein [7][8][9][10][11], and the three NAbs 2F5, 4E10 and Z13 are directed against the transmembrane gp41 protein [12][13][14]. Passive immunotherapy studies using combinations of some of these mAbs have resulted in protection against intravenous and/or mucosal simianhuman immunodeficiency virus (SHIV) challenge in monkeys [15][16][17][18], In addition, 2F5 and/ or 4E10 plus 2G12 immunotherapy have resulted in reduced viremia in established HIV-1 infection or delay of HIV-1 rebound in individuals undergoing interrupted antiretroviral treatment (ART) [19,20].…”

The good and evil of complement activation in HIV-1 infection

“…46 Indeed, Abs with potent neutralizing activity against a broad range of HIV-1 strains across HIV-1 clades have been found in HIV-1-infected individuals. [54][55][56][57][58][59][60] Among these nAbs, 2G12, 2F5 and 4E10 are three of the most broadly used Abs cloned from HIV-1-infected patients. 54,55,57,58,[61][62][63][64] 2G12 recognizes a unique mannosedependent epitope within gp120, 55,61,[65][66][67] while binding sites of 2F5 and 4E10 lie within a well-defined region of the membrane-proximal external region of gp41.…”

“…[54][55][56][57][58][59][60] Among these nAbs, 2G12, 2F5 and 4E10 are three of the most broadly used Abs cloned from HIV-1-infected patients. 54,55,57,58,[61][62][63][64] 2G12 recognizes a unique mannosedependent epitope within gp120, 55,61,[65][66][67] while binding sites of 2F5 and 4E10 lie within a well-defined region of the membrane-proximal external region of gp41. 54,57,58,60,68 Passive immunization with a cocktail of these three human monoclonal Abs was effective in animal models, i.e., it conferred protection against intravenous, intravaginal or oral challenge with simian human immunodeficiency virus (a monkey HIV-1 analog) in rhesus macaques.…”