Immune perturbations in HIV-1-infected individuals who make broadly neutralizing antibodies

M Anthony Moody; Isabela Pedroza-Pacheco; Nathan A Vandergrift; Cecilia Chui; Krissey E Lloyd; Robert Parks; Kelly A Soderberg; Ane T Ogbe; Myron S Cohen; Hua-Xin Liao; Feng Gao; Andrew J McMichael; David C Montefiori; Laurent Verkoczy; Garnett Kelsoe; Jinghe Huang; Patrick R Shea; Mark Connors; Persephone Borrow; Barton F Haynes

doi:10.1126/sciimmunol.aag0851

Immune perturbations in HIV-1-infected individuals who make broadly neutralizing antibodies

Sci Immunol. 2016 Jul 29;1(1):aag0851. doi: 10.1126/sciimmunol.aag0851. Epub 2016 Jul 29.

Authors

M Anthony Moody^{1

2

3}, Isabela Pedroza-Pacheco⁴, Nathan A Vandergrift^{5

6}, Cecilia Chui⁴, Krissey E Lloyd⁵, Robert Parks⁵, Kelly A Soderberg⁵, Ane T Ogbe⁴, Myron S Cohen⁷, Hua-Xin Liao^{5

6}, Feng Gao^{5

6}, Andrew J McMichael⁴, David C Montefiori⁸, Laurent Verkoczy^{5

6

9}, Garnett Kelsoe^{5

2}, Jinghe Huang¹⁰, Patrick R Shea¹¹, Mark Connors¹⁰, Persephone Borrow¹², Barton F Haynes^{1

2

6}

Affiliations

¹ Duke University Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA. [email protected] [email protected] [email protected].
² Department of Immunology, Duke University School of Medicine, Durham, NC 27710, USA.
³ Department of Pediatrics, Duke University School of Medicine, Durham, NC 27710, USA.
⁴ Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7FZ, UK.
⁵ Duke University Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
⁶ Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.
⁷ University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁸ Department of Surgery, Duke University School of Medicine, Durham, NC 27710, USA.
⁹ Department of Pathology, Duke University School of Medicine, Durham, NC 27710, USA.
¹⁰ Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20814, USA.
¹¹ Institute for Genomic Medicine, Columbia University, New York, NY 10032, USA.
¹² Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7FZ, UK. [email protected] [email protected] [email protected].

Abstract

Induction of broadly neutralizing antibodies (bnAbs) is a goal of HIV-1 vaccine development. bnAbs occur in some HIV-1-infected individuals and frequently have characteristics of autoantibodies. We have studied cohorts of HIV-1-infected individuals who made bnAbs and compared them with those who did not do so, and determined immune traits associated with the ability to produce bnAbs. HIV-1-infected individuals with bnAbs had a higher frequency of blood autoantibodies, a lower frequency of regulatory CD4⁺ T cells, a higher frequency of circulating memory T follicular helper CD4⁺ cells, and a higher T regulatory cell level of programmed cell death-1 expression compared with HIV-1-infected individuals without bnAbs. Thus, induction of HIV-1 bnAbs may require vaccination regimens that transiently mimic immunologic perturbations in HIV-1-infected individuals.

Abstract

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