Phenotypic and functional evaluation of T cell responses after intradermal immunization with LTR192G, an attenuated form of the enterotoxigenic E. coli (ETEC) labile toxin (LT), as an adjuvant for an ETEC vaccine (VAC8P.1004)

Abstract

Abstract The skin is an appealing route for delivery of vaccines. It is easily accessible, is rich in antigen presenting cells (i.e. dendritic cells), and several reports have shown that intradermal (ID) vaccination can use less antigen (dose sparing). However, few new adjuvants have been developed and tested for skin immunization. Here, we report our findings on the evaluation of the T cell response after immunization of volunteers with two prototype vaccines against ETEC given ID with LTR192G. Volunteers were immunized on days 0, 21 and 42 with the tip adhesin of the class 5a CFA/I fimbriae, CfaE, or an adhesin-toxoid chimera protein, CfaE-sCTA2/LTB5, admixed with the adjuvant. We found marked activation of LTB- and CfaE-specific CD4+ T cells post-immunization as measured by CD69 upregulation. Within the LTB-specific CD4+ population, we found a greater frequency of skin-homing CCR4+ cells, which is consistent with the route of immunization and a strong response to LTR192G. In addition, there was a higher frequency of LTB-specific CD4+ T cells with an effector memory phenotype. The frequency of CfaE-specific IFNγ+ CD4+ T cells was significantly higher post-immunization and was validated by high levels of IFNγ in CfaE-stimulated supernatants. Cytokine analysis also revealed higher levels of CfaE-specific IL-6 secretion compared to LTB. Taken together, the data demonstrate a strong CD4+ T cell response was generated to both antigen and adjuvant after ID immunization.