Potent and broad neutralization of HIV-1 by a llama antibody elicited by immunization.
Llamas (Lama glama) naturally produce heavy chain-only antibodies (Abs) in addition to conventional Abs. The variable regions (VHH) in these heavy chain-only Abs demonstrate comparable affinity and specificity for antigens to conventional immunoglobulins despite their much smaller size. To date, immunizations in humans and animal models have yielded only Abs with limited ability to neutralize HIV-1. In this study, a VHH phagemid library generated from a llama that was multiply immunized with recombinant trimeric HIV-1 envelope proteins (Envs) was screened directly for HIV-1 neutralization. One VHH, L8CJ3 (J3), neutralized 96 of 100 tested HIV-1 strains, encompassing subtypes A, B, C, D, BC, AE, AG, AC, ACD, CD, and G. J3 also potently neutralized chimeric simian-HIV strains with HIV subtypes B and C Env. The sequence of J3 is highly divergent from previous anti-HIV-1 VHH and its own germline sequence. J3 achieves broad and potent neutralization of HIV-1 via interaction with the CD4-binding site of HIV-1 Env. This study may represent a new benchmark for immunogens to be included in B cell-based vaccines and supports the development of VHH as anti-HIV-1 microbicides.
Wohl Virion Centre, University College London, London WC1E 6BT, England, UK.
Laura E
LE
McCoy
Anna Forsman
AF
Quigley
Nika M
NM
Strokappe
Bianca
B
Bulmer-Thomas
Michael S
MS
Seaman
Daniella
D
Mortier
Lucy
L
Rutten
Nikita
N
Chander
Carolyn J
CJ
Edwards
Robin
R
Ketteler
David
D
Davis
Theo
T
Verrips
Robin A
RA
Weiss
D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000915:Antibody Affinity; D015704:CD4 Antigens / Q000378:metabolism; D002161:Camelids, New World / Q000276:immunology*; D000939:Epitopes / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology; D009500:Neutralization Tests; D019151:Peptide Library; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology
D057134:Antibodies, Neutralizing; D015704:CD4 Antigens; D000939:Epitopes; D007135:Immunoglobulin Variable Region; D019151:Peptide Library; D011994:Recombinant Proteins; D019444:Vaccines, DNA; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1