Cooperation of B cell lineages in induction of HIV-1-broadly neutralizing antibodies

Feng Gao; Mattia Bonsignori; Hua-Xin Liao; Amit Kumar; Shi-Mao Xia; Xiaozhi Lu; Fangping Cai; Kwan-Ki Hwang; Hongshuo Song; Tongqing Zhou; Rebecca M Lynch; S Munir Alam; M Anthony Moody; Guido Ferrari; Mark Berrong; Garnett Kelsoe; George M Shaw; Beatrice H Hahn; David C Montefiori; Gift Kamanga; Myron S Cohen; Peter Hraber; Peter D Kwong; Bette T Korber; John R Mascola; Thomas B Kepler; Barton F Haynes

doi:10.1016/j.cell.2014.06.022

Cooperation of B cell lineages in induction of HIV-1-broadly neutralizing antibodies

Cell. 2014 Jul 31;158(3):481-91. doi: 10.1016/j.cell.2014.06.022. Epub 2014 Jul 24.

Authors

Feng Gao¹, Mattia Bonsignori², Hua-Xin Liao², Amit Kumar², Shi-Mao Xia², Xiaozhi Lu², Fangping Cai², Kwan-Ki Hwang², Hongshuo Song², Tongqing Zhou³, Rebecca M Lynch³, S Munir Alam², M Anthony Moody², Guido Ferrari², Mark Berrong², Garnett Kelsoe², George M Shaw⁴, Beatrice H Hahn⁴, David C Montefiori², Gift Kamanga⁵, Myron S Cohen⁶, Peter Hraber⁷, Peter D Kwong³, Bette T Korber⁷, John R Mascola³, Thomas B Kepler⁸, Barton F Haynes⁹

Affiliations

¹ Duke University Human Vaccine Institute, Departments of Medicine, Surgery, Pediatrics and Immunology, Duke University School of Medicine, Durham NC 27710, USA; The Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery at Duke University, Durham NC 27710, USA. Electronic address: fgao@duke.edu.
² Duke University Human Vaccine Institute, Departments of Medicine, Surgery, Pediatrics and Immunology, Duke University School of Medicine, Durham NC 27710, USA; The Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery at Duke University, Durham NC 27710, USA.
³ Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
⁴ Departments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
⁵ UNC Project, Lilongwe, Malawi; Departments of Health Policy and Management, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁶ Departments of Medicine, Epidemiology and Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁷ Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM 87544, USA.
⁸ Department of Microbiology, Boston University, Boston, MA 02215, USA.
⁹ Duke University Human Vaccine Institute, Departments of Medicine, Surgery, Pediatrics and Immunology, Duke University School of Medicine, Durham NC 27710, USA; The Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery at Duke University, Durham NC 27710, USA. Electronic address: barton.haynes@duke.edu.

Abstract

Development of strategies for induction of HIV-1 broadly neutralizing antibodies (bnAbs) by vaccines is a priority. Determining the steps of bnAb induction in HIV-1-infected individuals who make bnAbs is a key strategy for immunogen design. Here, we study the B cell response in a bnAb-producing individual and report cooperation between two B cell lineages to drive bnAb development. We isolated a virus-neutralizing antibody lineage that targeted an envelope region (loop D) and selected virus escape mutants that resulted in both enhanced bnAb lineage envelope binding and escape mutant neutralization-traits associated with increased B cell antigen drive. Thus, in this individual, two B cell lineages cooperated to induce the development of bnAbs. Design of vaccine immunogens that simultaneously drive both helper and broadly neutralizing B cell lineages may be important for vaccine-induced recapitulation of events that transpire during the maturation of neutralizing antibodies in HIV-1-infected individuals.

Publication types

Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

MeSH terms

AIDS Vaccines / chemistry*
AIDS Vaccines / immunology*
Amino Acid Sequence
Antibodies, Neutralizing / immunology*
B-Lymphocytes / immunology
HIV Antibodies / immunology*
HIV-1 / physiology*
Immune Evasion
Models, Molecular
Molecular Sequence Data
Mutation
Sequence Alignment
env Gene Products, Human Immunodeficiency Virus / genetics
env Gene Products, Human Immunodeficiency Virus / immunology

Substances

AIDS Vaccines
Antibodies, Neutralizing
HIV Antibodies
env Gene Products, Human Immunodeficiency Virus

Associated data

GENBANK/KM052327
GENBANK/KM052328
GENBANK/KM052329
GENBANK/KM052330
GENBANK/KM052331
GENBANK/KM052332
GENBANK/KM052333
GENBANK/KM052334
GENBANK/KM052335
GENBANK/KM052336
GENBANK/KM052337
GENBANK/KM052338
GENBANK/KM052339
GENBANK/KM052340
GENBANK/KM052341
GENBANK/KM052342
GENBANK/KM052343
GENBANK/KM052344

Abstract

Publication types

MeSH terms

Substances

Associated data

Grants and funding