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Abstract
Polyclonal Caprine IgG PEHRG214 (HRG): Anti-HIV Activity and Mapping of Novel Antibody Specificities
Sanford J.1, Dezube B.2, Perera T.1, Crumpacker C.2, Gelder F.1
1Virionyx, Auckland, New Zealand, 2Beth Israel Deaconess Medical Center, Boston, United States of America
Introduction: HRG is a novel polyclonal caprine IgG anti-HIV preparation, which has been administered intravenously to HIV-infected patients in single and multi-dose trials. HRG demonstrated anti-retroviral activity in some patients on HAART, who were failing virologically. We sought to characterize the anti-HIV activity of HRG and to map the antibody specificities present in it.
Methods: Anti-HIV activity of HRG was evaluated, employing an ELISA assay and western Blots. HIV neutralization activity was measured. Antibody specificities present in HRG were mapped employing overlapping complete peptide sets for HIV-1 MN env and HXB2 gag.
Results: HRG contained strong anti-HIV activity with positive ELISA results at concentrations >10 mg caprine IgG/ml. Western blot demonstrated strong reactivity against all major HIV-1 epitopes including gp120, gp41, p24, p17, p55 and p66; and all major HIV-2 epitopes including gp140, gp105, p56, p26 and p16. HRG demonstrated effective complement dependent anti-HIV neutralizing activity in vitro against both laboratory-adapted strains and primary isolates with CXCR4 or CCR5 receptor dependence (SE364, clade C, CCR5; ROK39, clade A, CCR5; NL43, clade B, CXCR4, molecular clone; 228200, clade B, CXCR4). Neutralization was concentration dependent with >90% neutralization observed in all cases at an HRG concentration of 250 mg/ml. Peptide mapping studies demonstrated HRG reacted to 4 unique epitopes on HIV-1; 1 on gp160, 2 on p17 and 1 on p24 that have not been described previously in human sera. Moreover HRG reacted to 8 epitopes on HIV-1 that are shared with human helper cell epitopes, and 6 that are shared with human helper cell and/or human antibody epitopes.
Conclusions: HRG contains potent anti-HIV neutralizing activity. Correlation of HRG reactivities with human anti-HIV reactivities demonstrated novel specificities unique to HRG, not previously recognized by either human anti-HIV sera or helper cells. These novel specificities may in part be responsible for the anti-HIV activity observed in previously reported clinical trials.
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