Lack of B cell dysfunction is associated with functional, gp120-dominant antibody responses in breast milk of simian immunodeficiency virus-infected African green monkeys.

dc.contributor.author

Amos, Joshua D

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Wilks, Andrew B

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Fouda, Genevieve G

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Smith, Shannon D

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Colvin, Lisa

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Mahlokozera, Tatenda

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Ho, Carrie

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Beck, Krista

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Overman, R Glenn

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DeMarco, C Todd

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Hodge, Terry L

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LaBranche, Celia C

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Montefiori, David C

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Denny, Thomas N

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Liao, Hua-Xin

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Tomaras, Georgia D

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Moody, M Anthony

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Permar, Sallie R

dc.coverage.spatial

United States

dc.date.accessioned

2017-06-01T20:24:34Z

dc.date.available

2017-06-01T20:24:34Z

dc.date.issued

2013-10

dc.description.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.

dc.identifier

https://www.ncbi.nlm.nih.gov/pubmed/23926338

dc.identifier

JVI.01887-13

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1098-5514

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https://hdl.handle.net/10161/14724

dc.language

eng

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American Society for Microbiology

dc.relation.ispartof

J Virol

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10.1128/JVI.01887-13

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Animals

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Antibodies, Viral

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B-Lymphocytes

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Cercopithecus aethiops

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Female

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HIV Infections

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Humans

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Macaca mulatta

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Membrane Glycoproteins

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Milk, Human

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Simian Acquired Immunodeficiency Syndrome

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Simian Immunodeficiency Virus

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Viral Envelope Proteins

dc.title

Lack of B cell dysfunction is associated with functional, gp120-dominant antibody responses in breast milk of simian immunodeficiency virus-infected African green monkeys.

dc.type

Journal article

duke.contributor.orcid

LaBranche, Celia C|0000-0002-6653-6655

duke.contributor.orcid

Montefiori, David C|0000-0003-0856-6319

duke.contributor.orcid

Tomaras, Georgia D|0000-0001-8076-1931

duke.contributor.orcid

Moody, M Anthony|0000-0002-3890-5855

pubs.author-url

https://www.ncbi.nlm.nih.gov/pubmed/23926338

pubs.begin-page

11121

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11134

pubs.issue

20

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Basic Science Departments

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Clinical Science Departments

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Duke

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Duke Human Vaccine Institute

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Immunology

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Institutes and Centers

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Medicine

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Medicine, Duke Human Vaccine Institute

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Molecular Genetics and Microbiology

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Pediatrics

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Pediatrics, Infectious Diseases

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School of Medicine

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Surgery

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Surgery, Surgical Sciences

pubs.publication-status

Published

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87

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