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. Issue 11 (4th March 2020)

• Record Type: Journal Article
• Authors: Gary, E.N.; Kathuria, N.; Makurumidze, G.; Curatola, A.; Ramamurthi, A.; Bernui, M.E.; Myles, D.; Yan, J.; Pankhong, P.; Muthumani, K.; Haddad, E.; Humeau, L.; Weiner, D.B.; Kutzler, M.A.
• Is Part Of: Vaccine. Volume 38:Issue 11(2020)
• Page Start: 2626
• Page End: 2635
• Publication Date: 2020-03-04
• Subjects: CCL28/MEC -- CCR10 -- DNA vaccine -- Mucosal IgA antibody -- In vivo electroporation; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2020.01.023
• Languages: English
• ISSNs: 0264-410X

Abstract

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.