HIV antibodies. Antigen modification regulates competition of broad and narrow neutralizing HIV antibodies

Some HIV-infected individuals develop broadly neutralizing antibodies (bNAbs), whereas most develop antibodies that neutralize only a narrow range of viruses (nNAbs). bNAbs, but not nNAbs, protect animals from experimental infection and are likely a key component of an effective vaccine. nNAbs and b...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2014-12, Vol.346 (6215), p.1380-1383
Main Authors: McGuire, Andrew T, Dreyer, Anita M, Carbonetti, Sara, Lippy, Adriana, Glenn, Jolene, Scheid, Johannes F, Mouquet, Hugo, Stamatatos, Leonidas
Format: Article
Language:English
Subjects:
AIDS Vaccines - immunology
Antibodies, Neutralizing - immunology
Antibody Affinity
B-Lymphocytes - immunology
Binding, Competitive
env Gene Products, Human Immunodeficiency Virus - chemistry
env Gene Products, Human Immunodeficiency Virus - genetics
env Gene Products, Human Immunodeficiency Virus - immunology
Epitopes - immunology
HIV Antibodies - genetics
HIV Antibodies - immunology
HIV-1 - immunology
Humans
Lymphocyte Activation
Models, Molecular
Receptors, Antigen, B-Cell - genetics
Receptors, Antigen, B-Cell - immunology
Recombinant Proteins - immunology
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Summary:Some HIV-infected individuals develop broadly neutralizing antibodies (bNAbs), whereas most develop antibodies that neutralize only a narrow range of viruses (nNAbs). bNAbs, but not nNAbs, protect animals from experimental infection and are likely a key component of an effective vaccine. nNAbs and bNAbs target the same regions of the viral envelope glycoprotein (Env), but for reasons that remain unclear only nNAbs are elicited by Env immunization. We show that in contrast to germline-reverted (gl) bNAbs, glnNAbs recognized diverse recombinant Envs. Moreover, owing to binding affinity differences, nNAb B cell progenitors had an advantage in becoming activated and internalizing Env compared with bNAb B cell progenitors. We then identified an Env modification strategy that minimized the activation of nNAb B cells targeting epitopes that overlap those of bNAbs.
ISSN:1095-9203
DOI:10.1126/science.1259206