1. Cooperation of B Cell Lineages in Induction of HIV-1-Broadly Neutralizing Antibodies
- Author
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Hua-Xin Liao, Shi Mao Xia, Hongshuo Song, M. Anthony Moody, John R. Mascola, Rebecca M. Lynch, Barton F. Haynes, Kwan Ki Hwang, S. Munir Alam, Fangping Cai, Gift Kamanga, Peter D. Kwong, David C. Montefiori, Xiaozhi Lu, Myron S. Cohen, Feng Gao, Mattia Bonsignori, Tongqing Zhou, Amit Kumar, Bette T. Korber, Guido Ferrari, George M. Shaw, Peter T. Hraber, Mark Berrong, Thomas B. Kepler, Beatrice H. Hahn, and Garnett Kelsoe
- Subjects
Models, Molecular ,Immunogen ,Lineage (evolution) ,Mutant ,Molecular Sequence Data ,Biology ,HIV Antibodies ,medicine.disease_cause ,General Biochemistry, Genetics and Molecular Biology ,Virus ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Amino Acid Sequence ,B cell ,030304 developmental biology ,Immune Evasion ,AIDS Vaccines ,0303 health sciences ,Mutation ,B-Lymphocytes ,Biochemistry, Genetics and Molecular Biology(all) ,env Gene Products, Human Immunodeficiency Virus ,Virology ,Antibodies, Neutralizing ,3. Good health ,medicine.anatomical_structure ,biology.protein ,HIV-1 ,Antibody ,Sequence Alignment ,030217 neurology & neurosurgery - Abstract
SummaryDevelopment 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.
- Published
- 2014
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