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3 results on '"Kwan-Ki Hwang"'

1. A Zika virus-specific IgM elicited in pregnancy exhibits ultrapotent neutralization

Author

Tulika Singh, Kwan-Ki Hwang, Andrew S. Miller, Rebecca L. Jones, Cesar A. Lopez, Sarah J. Dulson, Camila Giuberti, Morgan A. Gladden, Itzayana Miller, Helen S. Webster, Joshua A. Eudailey, Kan Luo, Tarra Von Holle, Robert J. Edwards, Sarah Valencia, Katherine E. Burgomaster, Summer Zhang, Jesse F. Mangold, Joshua J. Tu, Maria Dennis, S. Munir Alam, Lakshmanane Premkumar, Reynaldo Dietze, Theodore C. Pierson, Eng Eong Ooi, Helen M. Lazear, Richard J. Kuhn, Sallie R. Permar, and Mattia Bonsignori

Subjects
Mice, Epitopes, Pregnancy, Zika Virus Infection, Neutralization Tests, Immunoglobulin G, Animals, Female, Zika Virus, Antibodies, Viral, Antibodies, Neutralizing, General Biochemistry, Genetics and Molecular Biology
Abstract

Congenital Zika virus (ZIKV) infection results in neurodevelopmental deficits in up to 14% of infants born to ZIKV-infected mothers. Neutralizing antibodies are a critical component of protective immunity. Here, we demonstrate that plasma IgM contributes to ZIKV immunity in pregnancy, mediating neutralization up to 3 months post-symptoms. From a ZIKV-infected pregnant woman, we isolated a pentameric ZIKV-specific IgM (DH1017.IgM) that exhibited ultrapotent ZIKV neutralization dependent on the IgM isotype. DH1017.IgM targets an envelope dimer epitope within domain II. The epitope arrangement on the virion is compatible with concurrent engagement of all ten antigen-binding sites of DH1017.IgM, a solution not available to IgG. DH1017.IgM protected mice against viremia upon lethal ZIKV challenge more efficiently than when expressed as an IgG. Our findings identify a role for antibodies of the IgM isotype in protection against ZIKV and posit DH1017.IgM as a safe and effective candidate immunotherapeutic, particularly during pregnancy.

Published
2022

2. Cooperation of B Cell Lineages in Induction of HIV-1-Broadly Neutralizing Antibodies

Author

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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3. Cooperation of B Cell Lineages in Induction of HIV-1-Broadly Neutralizing Antibodies.

Author

Feng Gao, Bonsignori, Mattia, Hua-Xin Liao, Kumar, Amit, Shi-Mao Xia, Xiaozhi Lu, Fangping Cai, Kwan-Ki Hwang, Hongshuo Song, Tongqing Zhou, Lynch, Rebecca M., Alam, S. Munir, Moody, M. Anthony, Ferrari, Guido, Berrong, Mark, Kelsoe, Garnett, Shaw, George M., Hahn, Beatrice H., Montefiori, David C., and Kamanga, Gift

Subjects
*B cells, *ANTIGEN-antibody reactions, *NEUTRALIZATION (Chemistry), *HIV prevention, *HIV antibodies, *AIDS vaccines
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. [ABSTRACT FROM AUTHOR]

Published
2014
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