Combined HIV-1 Envelope Systemic and Mucosal Immunization of Lactating Rhesus Monkeys Induces a Robust Immunoglobulin A Isotype B Cell Response in Breast Milk.
| dc.contributor.author | Nelson, Cody S | |
| dc.contributor.author | Pollara, Justin | |
| dc.contributor.author | Kunz, Erika L | |
| dc.contributor.author | Jeffries, Thomas L | |
| dc.contributor.author | Duffy, Ryan | |
| dc.contributor.author | Beck, Charles | |
| dc.contributor.author | Stamper, Lisa | |
| dc.contributor.author | Wang, Minyue | |
| dc.contributor.author | Shen, Xiaoying | |
| dc.contributor.author | Pickup, David J | |
| dc.contributor.author | Staats, Herman F | |
| dc.contributor.author | Hudgens, Michael G | |
| dc.contributor.author | Kepler, Thomas B | |
| dc.contributor.author | Montefiori, David C | |
| dc.contributor.author | Moody, M Anthony | |
| dc.contributor.author | Tomaras, Georgia D | |
| dc.contributor.author | Liao, Hua-Xin | |
| dc.contributor.author | Haynes, Barton F | |
| dc.contributor.author | Ferrari, Guido | |
| dc.contributor.author | Fouda, Genevieve GA | |
| dc.contributor.author | Permar, Sallie R | |
| dc.contributor.editor | Silvestri, G | |
| dc.date.accessioned | 2024-09-03T13:18:07Z | |
| dc.date.available | 2024-09-03T13:18:07Z | |
| dc.date.issued | 2016-05 | |
| dc.description.abstract | UnlabelledMaternal vaccination to induce anti-HIV immune factors in breast milk is a potential intervention to prevent postnatal HIV-1 mother-to-child transmission (MTCT). We previously demonstrated that immunization of lactating rhesus monkeys with a modified vaccinia Ankara (MVA) prime/intramuscular (i.m.) protein boost regimen induced functional IgG responses in milk, while MVA prime/intranasal (i.n.) boost induced robust milk Env-specific IgA responses. Yet, recent studies have suggested that prevention of postnatal MTCT may require both Env-specific IgA and functional IgG responses in milk. Thus, to investigate whether both responses could be elicited by a combined systemic/mucosal immunization strategy, animals previously immunized with the MVA prime/i.n. boost regimen received an i.n./i.m. combined C.1086 gp120 boost. Remarkably, high-magnitude Env-specific IgA responses were observed in milk, surpassing those in plasma. Furthermore, 29% of vaccine-elicited Env-specific B cells isolated from breast milk were IgA isotype, in stark contrast to the overwhelming predominance of IgG isotype Env-specific B cells in breast milk of chronically HIV-infected women. A clonal relationship was identified between Env-specific blood and breast milk B cells, suggesting trafficking of that cell population between the two compartments. Furthermore, IgA and IgG monoclonal antibodies isolated from Env-specific breast milk B cells demonstrated diverse Env epitope specificities and multiple effector functions, including tier 1 neutralization, antibody-dependent cellular cytotoxicity (ADCC), infected cell binding, and inhibition of viral attachment to epithelial cells. Thus, maternal i.n./i.m. combined immunization is a novel strategy to enhance protective Env-specific IgA in milk, which is subsequently transferred to the infant via breastfeeding.ImportanceEfforts to increase the availability of antiretroviral therapy to pregnant and breastfeeding women in resource-limited areas have proven remarkably successful at reducing HIV vertical transmission rates. However, more than 200,000 children are infected annually due to failures in therapy implementation, monitoring, and adherence, nearly half by postnatal HIV exposure via maternal breast milk. Intriguingly, in the absence of antiretroviral therapy, only 10% of breastfed infants born to HIV-infected mothers acquire the virus, suggesting the existence of naturally protective immune factors in milk. Enhancement of these protective immune factors through maternal vaccination will be a critical strategy to reduce the global pediatric AIDS epidemic. We have previously demonstrated that a high magnitude of HIV Env-specific IgA in milk correlates with reduced risk of infant HIV acquisition. In this study, we describe a novel HIV vaccine regimen that induces potent IgA responses in milk and therefore could potentially protect against breast milk HIV MTCT. | |
| dc.identifier | JVI.00335-16 | |
| dc.identifier.issn | 0022-538X | |
| dc.identifier.issn | 1098-5514 | |
| dc.identifier.uri | ||
| dc.language | eng | |
| dc.publisher | American Society for Microbiology | |
| dc.relation.ispartof | Journal of virology | |
| dc.relation.isversionof | 10.1128/jvi.00335-16 | |
| dc.rights.uri | ||
| dc.subject | B-Lymphocytes | |
| dc.subject | Milk | |
| dc.subject | Animals | |
| dc.subject | Macaca mulatta | |
| dc.subject | Humans | |
| dc.subject | HIV-1 | |
| dc.subject | Immunoglobulin A | |
| dc.subject | Immunoglobulin G | |
| dc.subject | HIV Envelope Protein gp120 | |
| dc.subject | AIDS Vaccines | |
| dc.subject | HIV Antibodies | |
| dc.subject | Immunization, Secondary | |
| dc.subject | Antibody-Dependent Cell Cytotoxicity | |
| dc.subject | Immunity, Maternally-Acquired | |
| dc.subject | Immunity, Mucosal | |
| dc.subject | Lactation | |
| dc.subject | Pregnancy | |
| dc.subject | Infant | |
| dc.subject | Female | |
| dc.subject | Antibodies, Neutralizing | |
| dc.title | Combined HIV-1 Envelope Systemic and Mucosal Immunization of Lactating Rhesus Monkeys Induces a Robust Immunoglobulin A Isotype B Cell Response in Breast Milk. | |
| dc.type | Journal article | |
| duke.contributor.orcid | Duffy, Ryan|0000-0001-6071-1574 | |
| duke.contributor.orcid | Shen, Xiaoying|0000-0001-8076-1931|0000-0002-8387-3952 | |
| duke.contributor.orcid | Staats, Herman F|0000-0003-1039-1087 | |
| duke.contributor.orcid | Montefiori, David C|0000-0003-0856-6319 | |
| duke.contributor.orcid | Moody, M Anthony|0000-0002-3890-5855 | |
| duke.contributor.orcid | Tomaras, Georgia D|0000-0001-8076-1931 | |
| duke.contributor.orcid | Ferrari, Guido|0000-0001-7747-3349 | |
| pubs.begin-page | 4951 | |
| pubs.end-page | 4965 | |
| pubs.issue | 10 | |
| pubs.organisational-group | Duke | |
| pubs.organisational-group | School of Medicine | |
| pubs.organisational-group | Faculty | |
| pubs.organisational-group | Basic Science Departments | |
| pubs.organisational-group | Clinical Science Departments | |
| pubs.organisational-group | Institutes and Centers | |
| pubs.organisational-group | Integrative Immunobiology | |
| pubs.organisational-group | Molecular Genetics and Microbiology | |
| pubs.organisational-group | Medicine | |
| pubs.organisational-group | Pathology | |
| pubs.organisational-group | Pediatrics | |
| pubs.organisational-group | Surgery | |
| pubs.organisational-group | Medicine, Duke Human Vaccine Institute | |
| pubs.organisational-group | Medicine, General Internal Medicine | |
| pubs.organisational-group | Pediatrics, Infectious Diseases | |
| pubs.organisational-group | Surgery, Surgical Sciences | |
| pubs.organisational-group | Duke Cancer Institute | |
| pubs.organisational-group | Duke Human Vaccine Institute | |
| pubs.organisational-group | University Initiatives & Academic Support Units | |
| pubs.organisational-group | University Institutes and Centers | |
| pubs.organisational-group | Duke Global Health Institute | |
| pubs.organisational-group | Initiatives | |
| pubs.organisational-group | Duke Science & Society | |
| pubs.organisational-group | Duke Innovation & Entrepreneurship | |
| pubs.publication-status | Published | |
| pubs.volume | 90 |
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