Isolation of HIV-1-neutralizing mucosal monoclonal antibodies from human colostrum.
Abstract
BACKGROUND: Generation of potent anti-HIV antibody responses in mucosal compartments
is a potential requirement of a transmission-blocking HIV vaccine. HIV-specific, functional
antibody responses are present in breast milk, and these mucosal antibody responses
may play a role in protection of the majority of HIV-exposed, breastfeeding infants.
Therefore, characterization of HIV-specific antibodies produced by B cells in milk
could guide the development of vaccines that elicit protective mucosal antibody responses.
METHODS: We isolated B cells from colostrum of an HIV-infected lactating woman with
a detectable neutralization response in milk and recombinantly produced and characterized
the resulting HIV-1 Envelope (Env)-specific monoclonal antibodies (mAbs). RESULTS:
The identified HIV-1 Env-specific colostrum mAbs, CH07 and CH08, represent two of
the first mucosally-derived anti-HIV antibodies yet to be reported. Colostrum mAb
CH07 is a highly-autoreactive, weakly-neutralizing gp140-specific mAb that binds to
linear epitopes in the gp120 C5 region and gp41 fusion domain. In contrast, colostrum
mAb CH08 is a nonpolyreactive CD4-inducible (CD4i) gp120-specific mAb with moderate
breadth of neutralization. CONCLUSIONS: These novel HIV-neutralizing mAbs isolated
from a mucosal compartment provide insight into the ability of mucosal B cell populations
to produce functional anti-HIV antibodies that may contribute to protection against
virus acquisition at mucosal surfaces.
Type
Journal articleSubject
Antibodies, MonoclonalAntibodies, Neutralizing
B-Lymphocytes
Colostrum
Epitopes, B-Lymphocyte
Female
Fluorescent Antibody Technique, Indirect
HIV Antibodies
HIV Envelope Protein gp120
Humans
Neutralization Tests
Pregnancy
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https://hdl.handle.net/10161/10587Published Version (Please cite this version)
10.1371/journal.pone.0037648Publication Info
Friedman, James; Alam, S Munir; Shen, Xiaoying; Xia, Shi-Mao; Stewart, Shelley; Anasti,
Kara; ... Permar, Sallie R (2012). Isolation of HIV-1-neutralizing mucosal monoclonal antibodies from human colostrum.
PLoS One, 7(5). pp. e37648. 10.1371/journal.pone.0037648. Retrieved from https://hdl.handle.net/10161/10587.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
S. Munir Alam
Professor in Medicine
Research Interests.
The Alam laboratory’s primary research is focused on understanding the biophysical
properties of antigen-antibody binding and the molecular events of early B cell activation
using the HIV-1 broadly neutralizing antibody (bnAb) lineage models. We are studying
how HIV-1 Envelope proteins of varying affinities are sensed by B cells expressing
HIV-1 bnAbs or their germline antigen receptors and initiate early signaling events
for their activation. In the lon
Guido Ferrari
Professor in Surgery
The activities of the Ferrari Laboratory are based on both independent basic research
and immune monitoring studies. The research revolves around three main areas of interest:
class I-mediated cytotoxic CD8+ T cell responses, antibody-dependent cellular cytotoxicity
(ADCC), gene expression in NK and T cellular subsets upon infection with HIV-1. With
continuous funding over the last 11 years from the NIH and Bill & Melinda Gates Foundation
along with many other productive collaborations wi
Genevieve Giny Fouda
Associate Professor in Pediatrics
Dr Fouda's research interest is in understanding infant immune responses in the setting
of infection and vaccination. Her current work focuses on HIV mother to child transmission.
Barton Ford Haynes
Frederic M. Hanes Distinguished Professor of Medicine
Barton F. Haynes, M.D. is the Frederic M. Hanes Professor of Medicine and Immunology,
and Director of the Duke Human Vaccine Institute. Prior to leading the DHVI, Dr. Haynes
served as Chief of the Division of Rheumatology, Allergy and Clinical Immunology,
and later as Chair of the Department of Medicine. As Director of the Duke Human Vaccine
Institute, Bart Haynes is leading a team of investigators working on vaccines for
emerging infections, including tuberculosis, pandemic influenza, emergi
Garnett H. Kelsoe
James B. Duke Distinguished Professor of Immunology
1. Lymphocyte development and antigen-driven diversification of immunoglobulin and
T cell antigen receptor genes. 2. The germinal center reaction and mechanisms for
clonal selection and self - tolerance. The origins of autoimmunity. 3. Interaction
of innate- and adaptive immunity and the role of inflammation in lymphoid organogenesis.
4. The role of secondary V(D)J gene rearrangment in lymphocyte development and malignancies.
5. Mathematical modeling of immune responses,
Hua-Xin Liao
Adjunct Professor in the Department of Medicine
Dr. Liao is a Professor of Medicine and Research Director of Duke Human Vaccine Institute.
Dr. Liao is a MD virologistt rained in China. In early 1980’s, Dr. Liao made
major contributions to the first isolation of epidemic hemorrhagic fever virus (hataanvirus)
from Apodemus agraius using tissue culture in China. The successful identification
and isolation of Hataanvirus enabled the early diagnosis and treatment of the disease,
and advancement of HFRS research towards prevention by de
This author no longer has a Scholars@Duke profile, so the information shown here reflects
their Duke status at the time this item was deposited.
Michael Anthony Moody
Professor of Pediatrics
Tony Moody, MD is a Professor in the Department of Pediatrics, Division of Infectious
Diseases and Professor in the Department of Integrative Immunobiology at Duke University
Medical Center. Research in the Moody lab is focused on understanding the B cell responses
during infection, vaccination, and disease. The lab has become a resource for human
phenotyping, flow characterization, staining and analysis at the Duke Human Vaccine
Institute (DHVI). The Moody lab is currently funded to study in
Sallie Robey Permar
Adjunct Professor in the Department of Pathology
Dr. Permar's work focuses on the development of vaccines to prevent vertical transmission
of neonatal viral pathogens. She has utilized the nonhuman primate model of HIV/AIDS
to characterize the virus-specific immune responses and virus evolution in breast
milk and develop a maternal vaccine regimen for protection against breast milk transmission
of HIV. In addition, Dr. Permar's lab has advanced the understanding of HIV-specific
immune responses and virus evolution in vertically-transmitting an
Justin Joseph Pollara
Associate Professor in Surgery
Georgia Doris Tomaras
Professor in Surgery
Dr. Georgia Tomaras is a tenured Professor of Surgery, Professor of Immunology, Professor
of Molecular Genetics and Microbiology and is a Fellow of the American Academy of
Microbiology (AAM) and a Fellow of the American Association for the Advancement of
Science (AAAS). Dr. Tomaras is Co-Director of the Center for Human Systems Immunology
(CHSI) Duke University and Director of the Duke Center for AIDS Research (CFAR). Her
national and international leadership roles i
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