TY - JOUR
T1 - Highly potent HIV-specific antibody neutralization in vitro translates into effective protection against mucosal SHIV challenge in vivo
AU - Moldt, Brian
AU - Rakasz, Eva G.
AU - Schultz, Niccole
AU - Chan-Hui, Po Ying
AU - Swiderek, Kristine
AU - Weisgrau, Kimberly L.
AU - Piaskowski, Shari M.
AU - Bergman, Zachary
AU - Watkins, David I.
AU - Poignard, Pascal
AU - Burtona, Dennis R.
N1 - Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2012/11/13
Y1 - 2012/11/13
N2 - Most animal studies using passive administration of HIV broadly neutralizing monoclonal antibodies (bnMAbs) have associated protection against high-dose mucosal viral challenge with relatively high serum concentrations of antibody. We recently identified several bnMAbs remarkable for their in vitro potency against HIV. Of these bnMAbs, PGT121 is one of the most broad and potent antibodies isolated to date and shows 10- to 100-fold higher neutralizing activity than previously characterized bnMAbs. To evaluate the protective potency of PGT121 in vivo, we performed a protection study in rhesus macaques. Animals were i.v. administered 5 mg/kg, 1 mg/kg, or 0.2 mg/kg PGT121 24 h before being vaginally challenged with a single high dose of chimeric simian-human immunodeficiency virus (SHIV)SF162P3. Sterilizing immunity was achieved in all animals administered 5 mg/kg and 1 mg/kg and three of five animals administered 0.2 mg/kg PGT121, with corresponding average antibody serum concentrations of 95 μg/mL, 15 μg/mL, and 1.8 μg/mL, respectively. The results suggest that a protective serum concentration for PGT121 is in the single-digit μg/mL for SHIVSF162P3, showing that PGT121 can mediate sterilizing immunity at serum concentrations that are significantly lower than those observed in previous studies and that may be achievable through vaccination with the development of a suitable immunogen.
AB - Most animal studies using passive administration of HIV broadly neutralizing monoclonal antibodies (bnMAbs) have associated protection against high-dose mucosal viral challenge with relatively high serum concentrations of antibody. We recently identified several bnMAbs remarkable for their in vitro potency against HIV. Of these bnMAbs, PGT121 is one of the most broad and potent antibodies isolated to date and shows 10- to 100-fold higher neutralizing activity than previously characterized bnMAbs. To evaluate the protective potency of PGT121 in vivo, we performed a protection study in rhesus macaques. Animals were i.v. administered 5 mg/kg, 1 mg/kg, or 0.2 mg/kg PGT121 24 h before being vaginally challenged with a single high dose of chimeric simian-human immunodeficiency virus (SHIV)SF162P3. Sterilizing immunity was achieved in all animals administered 5 mg/kg and 1 mg/kg and three of five animals administered 0.2 mg/kg PGT121, with corresponding average antibody serum concentrations of 95 μg/mL, 15 μg/mL, and 1.8 μg/mL, respectively. The results suggest that a protective serum concentration for PGT121 is in the single-digit μg/mL for SHIVSF162P3, showing that PGT121 can mediate sterilizing immunity at serum concentrations that are significantly lower than those observed in previous studies and that may be achievable through vaccination with the development of a suitable immunogen.
KW - Animal model
KW - Antibody prophylaxis
KW - Passive transfer
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U2 - 10.1073/pnas.1214785109
DO - 10.1073/pnas.1214785109
M3 - Article
C2 - 23100539
AN - SCOPUS:84869232528
VL - 109
SP - 18921
EP - 18925
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 46
ER -