Immune checkpoint modulation enhances HIV-1 antibody induction

Eliciting protective titers of HIV-1 broadly neutralizing antibodies (bnAbs) is a goal of HIV-1 vaccine development, but current vaccine strategies have yet to induce bnAbs in humans. Many bnAbs isolated from HIV-1-infected individuals are encoded by immunoglobulin gene rearrangments with infrequent...

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Vydáno v:	Nature communications Ročník 11; číslo 1; s. 948 - 16
Hlavní autoři:	Bradley, Todd, Kuraoka, Masayuki, Yeh, Chen-Hao, Tian, Ming, Chen, Huan, Cain, Derek W., Chen, Xuejun, Cheng, Cheng, Ellebedy, Ali H., Parks, Robert, Barr, Maggie, Sutherland, Laura L., Scearce, Richard M., Bowman, Cindy M., Bouton-Verville, Hilary, Santra, Sampa, Wiehe, Kevin, Lewis, Mark G., Ogbe, Ane, Borrow, Persephone, Montefiori, David, Bonsignori, Mattia, Anthony Moody, M., Verkoczy, Laurent, Saunders, Kevin O., Ahmed, Rafi, Mascola, John R., Kelsoe, Garnett, Alt, Frederick W., Haynes, Barton F.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 19.02.2020 Nature Publishing Group Nature Portfolio
Témata:	38/1 45 45/91 631/250/2152/569 631/326/590 692/699/255/1901 AIDS Vaccines - administration & dosage AIDS Vaccines - immunology Animals Antibodies Antibodies, Blocking - administration & dosage Antibodies, Blocking - immunology Antibodies, Neutralizing - blood Antibodies, Neutralizing - immunology Antigens B-Lymphocytes - immunology Binding sites Blocking antibodies CD4 antigen CD4 Antigens - genetics CTLA-4 Antigen - antagonists & inhibitors CTLA-4 Antigen - immunology CTLA-4 protein env Gene Products, Human Immunodeficiency Virus - immunology Helper cells HIV HIV Antibodies - blood HIV Antibodies - immunology HIV Infections - immunology HIV-1 - immunology Human immunodeficiency virus Humanities and Social Sciences Humans Immune checkpoint Immune system Immunoglobulins Immunologic Factors - administration & dosage Immunologic Factors - immunology Lymphocyte Activation Macaca mulatta - immunology Mice Mice, Transgenic Modulation multidisciplinary Neutralizing PD-1 protein Precursors Receptors Receptors, OX40 - agonists Receptors, OX40 - immunology Science Science (multidisciplinary) T-Lymphocytes, Helper-Inducer - immunology Transcriptome Tumor necrosis factor Vaccination - methods Vaccine development Vaccines
ISSN:	2041-1723, 2041-1723
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Shrnutí:	Eliciting protective titers of HIV-1 broadly neutralizing antibodies (bnAbs) is a goal of HIV-1 vaccine development, but current vaccine strategies have yet to induce bnAbs in humans. Many bnAbs isolated from HIV-1-infected individuals are encoded by immunoglobulin gene rearrangments with infrequent naive B cell precursors and with unusual genetic features that may be subject to host regulatory control. Here, we administer antibodies targeting immune cell regulatory receptors CTLA-4, PD-1 or OX40 along with HIV envelope (Env) vaccines to rhesus macaques and bnAb immunoglobulin knock-in (KI) mice expressing diverse precursors of CD4 binding site HIV-1 bnAbs. CTLA-4 blockade augments HIV-1 Env antibody responses in macaques, and in a bnAb-precursor mouse model, CTLA-4 blocking or OX40 agonist antibodies increase germinal center B and T follicular helper cells and plasma neutralizing antibodies. Thus, modulation of CTLA-4 or OX40 immune checkpoints during vaccination can promote germinal center activity and enhance HIV-1 Env antibody responses. Elucidation of broadly neutralizing antibodies (bnAb) is a goal in HIV vaccine development. Here, Bradley et al. show that administration of CTLA-4 blocking antibody with vaccine antigens increases HIV-1 envelope antibody responses in macaques and a bnAb precursor mouse model.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-020-14670-w