Journal article
CCR10 expression is required for immunogenicity of a HIV-1env DNA vaccine encoding CCL28 to enhance HIV-1env-specific IgG and IgA at relevant mucosal sites (VAC7P.986)
The Journal of immunology (1950), v 192(1_Supplement)
01 May 2014
Abstract
Abstract Development of a vaccine that drives anti-viral mucosal B cell responses is critical for protection against HIV-1 infection. It is currently unknown whether triggering CCR10/CCL28 pathways in a DNA-based vaccine results in induction of HIV-1env specific B cell immunity at mucosal sites of infection. We hypothesized that co-immunization with HIV-1env/CCL28 molecular adjuvant would augment B cell responses at gastrointestinal and vaginal sites and require CCR10. CCL28 co-immunized WT mice displayed a significant enhancement of HIV-1env specific antibody titers in serum, feces and vaginal washes, and enhanced HIV-1 specific IgA responses were abrogated in CCR10KO mice. CCL28 co-immunization did not increase the breadth of linear B cell epitopes in WT mice, but augmented the dominant epitopes elicited by antigen immunization alone. The frequency of splenic and intestinal IgA+CD19+B220+CD138+CCR10+ plasmablasts was augmented in the CCL28 co-immunized WT mice over antigen-only immunized WT controls. The physiological relevance of these findings was confirmed in a NHP model of intravaginal SIVsmE660 challenge in which CCL28 co-immunization resulted in significant increases in serum/vaginal IgG/IgA, decrease in peak viral loads, significant suppression of viral titers over 120 days, and recovery of CD4 T cells. These data support a role for CCL28 in targeting protective anti-viral B cells to mucosal sites when delivered as molecular adjuvants for HIV-1env DNA-based vaccines.
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Details
- Title
- CCR10 expression is required for immunogenicity of a HIV-1env DNA vaccine encoding CCL28 to enhance HIV-1env-specific IgG and IgA at relevant mucosal sites (VAC7P.986)
- Creators
- Michele Kutzler - Drexel UniversityNoshin Kathuria - Drexel UniversityAshley Curatola - Drexel UniversityGetrude Makurumidze - Drexel UniversityDevon Myles - University of PennsylvaniaKar MuthumaniAlbert Sylvester - Drexel UniversityArielle Ginsberg - University of PennsylvaniaNatalie Hutnick - University of PennsylvaniaZina Moldoveanu - University of Alabama at BirminghamMeredith Hunter - 5Tulane National Primate Center, Covington, LAAmir Khan - Inovio Pharmaceuticals (United States)Niranjan Sardesai - Inovio Pharmaceuticals (United States)Jiri Mestecky - University of Alabama at BirminghamPreston Marx - 5Tulane National Primate Center, Covington, LADavid Weiner - Drexel University
- Publication Details
- The Journal of immunology (1950), v 192(1_Supplement)
- Publisher
- American Association of Immunologists (AAI)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Infectious Diseases (and HIV Medicine)
- Other Identifier
- 991020550347904721