Lack of B cell dysfunction is associated with functional, gp120-dominant antibody responses in breast milk of simian immunodeficiency virus-infected African green monkeys.
Abstract
The design of an effective vaccine to reduce the incidence of mother-to-child transmission
(MTCT) of human immunodeficiency virus (HIV) via breastfeeding will require identification
of protective immune responses that block postnatal virus acquisition. Natural hosts
of simian immunodeficiency virus (SIV) sustain nonpathogenic infection and rarely
transmit the virus to their infants despite high milk virus RNA loads. This is in
contrast to HIV-infected women and SIV-infected rhesus macaques (RhMs), nonnatural
hosts which exhibit higher rates of postnatal virus transmission. In this study, we
compared the systemic and mucosal B cell responses of lactating, SIV-infected African
green monkeys (AGMs), a natural host species, to that of SIV-infected RhMs and HIV-infected
women. AGMs did not demonstrate hypergammaglobulinemia or accumulate circulating memory
B cells during chronic SIV infection. Moreover, the milk of SIV-infected AGMs contained
higher proportions of naive B cells than RhMs. Interestingly, AGMs exhibited robust
milk and plasma Env binding antibody responses that were one to two logs higher than
those in RhMs and humans and demonstrated autologous neutralizing responses in milk
at 1 year postinfection. Furthermore, the plasma and milk Env gp120-binding antibody
responses were equivalent to or predominant over Env gp140-binding antibody responses
in AGMs, in contrast to that in RhMs and humans. The strong gp120-specific, functional
antibody responses in the milk of SIV-infected AGMs may contribute to the rarity of
postnatal transmission observed in natural SIV hosts.
Type
Journal articleSubject
AnimalsAntibodies, Viral
B-Lymphocytes
Cercopithecus aethiops
Female
HIV Infections
Humans
Macaca mulatta
Membrane Glycoproteins
Milk, Human
Simian Acquired Immunodeficiency Syndrome
Simian Immunodeficiency Virus
Viral Envelope Proteins
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https://hdl.handle.net/10161/14724Published Version (Please cite this version)
10.1128/JVI.01887-13Publication Info
Amos, Joshua D; Wilks, Andrew B; Fouda, Genevieve G; Smith, Shannon D; Colvin, Lisa;
Mahlokozera, Tatenda; ... Permar, Sallie R (2013). Lack of B cell dysfunction is associated with functional, gp120-dominant antibody
responses in breast milk of simian immunodeficiency virus-infected African green monkeys.
J Virol, 87(20). pp. 11121-11134. 10.1128/JVI.01887-13. Retrieved from https://hdl.handle.net/10161/14724.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
Thomas Norton Denny
Professor in Medicine
Thomas N. Denny, MSc, M.Phil, is the Chief Operating Officer of the Duke Human Vaccine
Institute (DHVI), Associate Dean for Duke Research and Discovery @RTP, and a Professor
of Medicine in the Department of Medicine at Duke University Medical Center. He is
also an Affiliate Member of the Duke Global Health Institute. Previously, he served
on the Health Sector Advisory Council of the Duke University Fuquay School of Business.
Prior to joining Duke, he was an Associate Professor of Pathology, Labo
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.
Celia Crane LaBranche
Associate Professor Emeritus
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.
David Charles Montefiori
Professor in Surgery
Dr. Montefiori is Professor and Director of the Laboratory for HIV and COVID-19 Vaccine
Research & Development in the Department of Surgery, Division of Surgical Sciences
at Duke University Medical Center. His major research interests are viral immunology
and HIV and COVID-19 vaccine development, with a special emphasis on neutralizing
antibodies. Multiple aspects of HIV-1 neutralizing antibodies are studied in his laboratory,
including mechanisms of neutralization and escape,
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
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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