Parenteral vaccination protects against transcervical infection with Chlamydia trachomatis and generate tissue-resident T cells post-challenge

Abstract

The optimal protective immunity against Chlamydia trachomatis (C.t.) is still not fully resolved. One of the unresolved issues concerns the importance of resident immunity, since a recent study showed that optimal protection against a transcervical (TC) infection required genital tissue-resident memory T cells. An important question in the Chlamydia field is therefore if a parenteral vaccine strategy, inducing only circulating immunity primed at a nonmucosal site, should be pursued by Chlamydia vaccine developers. To address this question we studied the protective efficacy of a parenteral Chlamydia vaccine, formulated in the Th1/ Th17 T cell-inducing adjuvant CAF01. We found that a parenteral vaccination induced significant protection against a TC infection and against development of chronic pathology. Protection correlated with rapid recruitment of Th1/Th17 T cells to the genital tract (GT), which efficiently prevented infection-driven generation of low quality Th1 or Th17 T cells, and instead maintained a pool of high quality multifunctional Th1/Th17 T cells in the GT throughout the infection. After clearance of the infection, a pool of these cells settled in the GT as tissue-resident Th1 and Th17 cells expressing CD69 but not CD103, CD49d, or CCR7, where they responded rapidly to a reinfection. These results show that a nonmucosal parenteral strategy inducing Th1 and Th17 T cells mediates protection against both infection with C.t. as well as development of chronic pathology, and lead to post-challenge protective tissue-resident memory immunity in the genital tract.npj Vaccines (2020) 5:7 ; https://doi.

The Many Faces of CD4+ T Cells: Immunological and Structural Characteristics

“…Additionally, Th1 CD4 + T cells may also produce IL-2 [ 35 , 48 ], IL-10 [ 49 , 50 ], TNF-α [ 51 ] and lymphotoxin [ 35 ]. Th1 cells can be found circulating within the periphery, and there is mounting evidence that Th1 CD4 + T cells can also express tissue resident phenotypes [ 52 , 53 ] and be found in tissues. IL-2 is known to be important in the generation of resident memory Th1 CD4 + T cells in the lungs of mice [ 52 ], and protective tissue resident CD69 + CD4 + Th1 cells can be generated by perinatal vaccination and found resident in the genital tract in humans [ 53 ].…”

A Novel Outbred Mouse Model to Study Lung Memory Immunological Response Induced by Pertussis Vaccines

“…Nevertheless, our study results demonstrate that parenteral immunization of mice, at least with a wP vaccine, elicited an effective distant mucosal response with generation of lung T RM T cells. Recent studies, consistent with our findings, demonstrated similar effective mucosal memory response following s.c. parenteral vaccination in the genital tract and nasal tissue (54,55). Furthermore, in this outbred mouse model of memory immunity, we observed that vaccination by the i.m.…”

Mucosal Vaccination with UV-Inactivated Chlamydia suis in Pre-Exposed Outbred Pigs Decreases Pathogen Load and Induces CD4 T-Cell Maturation into IFN-γ+ Effector Memory Cells

“…These cells have also been shown to correlate with protection [ 49 ]; moreover, they are essential for pathogen clearance [ 7 , 50 , 51 ]. During chlamydia infection in mice, naïve T cells differentiate into effector T cells in uterus-trafficking lymph nodes and these effector cells are then recruited to the mucosa of the genital tract to establish tissue-resident memory cells (T RM ) [ 21 , 52 , 53 ]. Furthermore, in 2015, Stary et al showed that the generation of “two waves of protective memory T cells,” tissue-resident CD4 T RM and circulating T CM and T EM cells, is required for optimal clearance of genital Ct infections [ 7 ].…”

“…This collaboration studied not only basic characteristics of the pig model relevant for translational Ct research, they also used their combined expertise for Ct vaccine development and demonstrated Ct vaccine efficacy and immunogenicity in naïve minipigs [ 10 ]. In their latest studies, the authors showed that protection against Ct genital infection in minipigs immunized with Ct vaccine formulated with CAF01 adjuvant was associated with cervical infiltration of CD4 + T cells [ 20 ] and tissue-resident memory CD4 + T cell infiltration into the uterus [ 21 ]. Käser et al provided a detailed view of the porcine T-cell immune response to Cs and Ct .…”