CD4⁺T Cells and Antibody Are Required for Optimal Major Outer Membrane Protein Vaccine-Induced Immunity toChlamydia muridarumGenital Infection

Abstract

Despite effective antimicrobial chemotherapy, control of Chlamydia trachomatis urogenital infection will likely require a vaccine. We have assessed the protective effect of an outer membrane protein-based vaccine by using a murine model of chlamydial genital infection. Female mice were first vaccinated with Chlamydia muridarum major outer membrane protein (MOMP) plus the adjuvants CpG-1826 and Montanide ISA 720; then they were challenged with C. muridarum. Vaccinated mice shed 2 log 10 to 3 log 10 fewer inclusion-forming units (IFU) than ovalbumin-vaccinated or naïve animals, resolved infection sooner, and had a lower incidence of hydrosalpinx. To determine the relative contribution of T cells to vaccine-induced protection, mice were vaccinated, depleted of CD4 ؉ or CD8 ؉ T cells, and then challenged vaginally with C. muridarum. Depletion of CD4 ؉ T cells, but not depletion of CD8 ؉ T cells, diminished vaccine-induced protection, with CD4-depleted mice shedding 2 log 10 to 4 log 10 more IFU than CD8-depleted or nondepleted mice. The contribution of antibodies to vaccine-induced protection was demonstrated by the absence of protective immunity in vaccinated B-cell-deficient mice and by a 2 log 10 to 3 log 10 decrease in bacterial shedding by mice passively administered an anti-MOMP serum. Thus, optimal protective immunity in this model of vaccine-induced protection depends on contributions from both CD4 ؉ T cells and antibody.

Genital Chlamydia trachomatis: Understanding the Roles of Innate and Adaptive Immunity in Vaccine Research

“…While there is ample evidence that CD4 ϩ T cells play an integral part in C. muridarum and C. trachomatis infection resolution (90)(91)(92)(93), the role for CD8 ϩ T cells has been controversial. Indeed, CD8…”

Vaccination againstChlamydiaGenital Infection Utilizing the MurineC. muridarumModel

“…Further studies into the mechanisms of the nMOMP vaccine-induced protective response revealed that both CD4 ϩ T cells and antibody are required for the nMOMP vaccine-induced protection (29). The passive transfer of the polyclonal anti-MOMP serum that is generated by vaccination was also shown to protect mice in a model of genital tract reinfection better than convalescent-phase serum from infection-immune animals (29).…”

“…The vaccine preparation containing nMOMP plus CpG-1826 and Montanide ISA 720 has been shown to induce protection not only against upper genital tract challenge in mice (80), but also against vaginal challenge with C. muridarum (29). Further studies into the mechanisms of the nMOMP vaccine-induced protective response revealed that both CD4 ϩ T cells and antibody are required for the nMOMP vaccine-induced protection (29).…”

A Peptide Containing T-Cell Epitopes of <i>Chlamydia trachomatis</i> Recombinant MOMP Induces Systemic and Mucosal Antibody Responses in Mice

“…CD4+ and CD8+ cells producing IFN-γ, as well as B cells are required to clear infection and prevent reinfection [3] CD4+ cells regulate B-cell production of neutralizing antibodies, which are important in preventing reinfection [22]. A recent study [23] highlighted that CD4+ T cells along with antibody contribute significantly to protective immunity during a Chlamydia infection as evidenced by the absence of protective immunity in vaccinated B-cell deficient mice challenged with C. trachomatis. We show that rMOMP-278 can, in the absence of an adjuvant, induce Th 1 antibodies in mice.…”