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Accepted (AM)Open Access (License Unspecified), Open
Journal article
CCR10 expression is required for the adjuvant activity of the mucosal chemokine CCL28 when delivered in the context of an HIV-1 Env DNA vaccine
Vaccine, v 38(11), pp 2626-2635
04 Mar 2020
PMID: 32057572
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
An effective prophylactic vaccine targeting HIV must induce a robust humoral response and must direct the bulk of this response to the mucosa-the primary site of HIV transmission. The chemokine, CCL28, is secreted by epithelial cells at mucosal surfaces and recruits′ cells expressing its receptor CCR10. CCR10 is predominantly expressed by IgA + ASCs. We hypothesized that co-immunization with plasmid DNA encoding consensus envelope antigens with plasmid-encoded CCL28 would enhance anti-HIV IgA responses at mucosal surfaces. Indeed, animals receiving pCCL28 and pEnvA/C had significantly increased HIV-specific IgA in fecal extract. Surprisingly, CCL28 co-immunization induced a significant increase in anti-HIV IgG in the serum in mice compared to those receiving pEnvA/C alone. These robust antibody responses were not associated with changes in the frequency of germinal center B cells but depended upon the expression of CCR10, as these responses we abolished in CCR10-deficient animals. Finally, immunization with CCL28 led to increased frequencies in HIV-specific CCR10 + and CCR10 + IgA + B cells in the small intestine and Peyer’s patches of vaccinated animals as compared to those receiving pEnvA/C alone. These data indicate that CCL28 administration can enhance antigen-specific humoral responses systemically and at mucosal surfaces.
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Details
- Title
- CCR10 expression is required for the adjuvant activity of the mucosal chemokine CCL28 when delivered in the context of an HIV-1 Env DNA vaccine
- Creators
- E.N. Gary - Drexel UniversityN. Kathuria - Drexel UniversityG. Makurumidze - Drexel UniversityA. Curatola - Drexel UniversityA. Ramamurthi - Drexel UniversityM.E. Bernui - Drexel UniversityD. Myles - The Department of Pathology and Laboratory Medicine, The University of Pennsylvania, Philadelphia, PA, United StatesJ. Yan - Inovio PharmaceuticalsP. Pankhong - University of PennsylvaniaK. Muthumani - The Wistar InstituteE. Haddad - Drexel UniversityL. Humeau - Inovio PharmaceuticalsD.B. Weiner - The Wistar InstituteM.A. Kutzler - Drexel University
- Publication Details
- Vaccine, v 38(11), pp 2626-2635
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Accounting; Infectious Diseases (and HIV Medicine)
- Web of Science ID
- WOS:000521654200025
- Scopus ID
- 2-s2.0-85079190964
- Other Identifier
- 991019168569804721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- Web of Science research areas
- Immunology
- Medicine, Research & Experimental