Immunogenicity of a vaccine formulated with the Chlamydia trachomatis serovar F, native major outer membrane protein in a nonhuman primate model

Abstract

To determine the ability of a vaccine formulated with the genital Chlamydia trachomatis, serovar F, native major outer membrane protein (Ct-F-nMOMP), to induce systemic and mucosal immune responses, rhesus macaques (Macaca mulatta) were immunized three times by the intramuscular (i.m.) and subcutaneous (s.c.) routes using CpG-2395 and Montanide ISA 720 VG, as adjuvants. As controls, another group of M. mulatta was immunized with ovalbumin instead of Ct-F-nMOMP using the same formulation and routes. High levels of Chlamydia-specific IgG and IgA antibodies were detected in plasma, vaginal washes, tears, saliva, and stools from the Ct-F-nMOMP immunized animals. Also, high neutralizing antibody titers were detected in the plasma from these animals. Monkeys immunized with ovalbumin had no detectable Chlamydia-specific antibodies. Furthermore, as measured by a lymphoproliferative assay, significant Chlamydia-specific cell-mediated immune responses were detected in the peripheral blood mononuclear cells (PBMC) from the rhesus macaques vaccinated with Ct-F-nMOMP when compared with the animals immunized with ovalbumin. In addition, the levels of two Th1 cytokines, IFN-γ and TNF-α, were significantly higher in the animals immunized with Ct-F-nMOMP when compared with those from the monkeys immunized with ovalbumin. To our knowledge, this is the first time that mucosal and systemic immune responses have been investigated in a nonhuman primate model using a subunit vaccine from a human genital C. trachomatis serovar.

Induction of mucosal immunity through systemic immunization: Phantom or reality?

“…immunization strategy, rhesus macaques vaccinated with a vaccine comprising of Chlamydia trachomatis serover F native major outer membrane protein (MOMP) with CpG-2395 and Montanide ISA 720 VG as adjuvants developed potent systemic and mucosal humoral and CMI responses with high levels of antigen-specific IgG and IgA in plasma and mucosal secretions (vaginal washes, tears, saliva and stools), as well as enhanced lymphocyte proliferation responses and IFN-g, TNF-a and IL-6 production by PBMCs. 68…”

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

“…A nonhuman primate model was used to demonstrate the efficacy of a vaccine formulated with native MOMP. Rhesus macaques that were immunized intramuscularly and subcutaneously along with the adjuvants CpG-2395 and Montanide ISA 720 produced high levels of Th1 cytokines (IFN-␥ and TNF-␣) and C. trachomatisspecific IgG and IgA (161). Drawbacks of subunit vaccines include the facts that extracting, refolding, and purifying protein complexes such as MOMP are very expensive and that purifications are not standardized, so differences in extraction methods may influence the conformation of the protein epitopes and the vaccine efficacy.…”

The Yin and Yang of Human Beta-Defensins in Health and Disease

“…Similarly, TLR2 has been implicated as a critical factor in CD4 + T cell responses to the outer membrane protein (OmpA) of Shigella flexneri (Pore et al, 2012). Moreover, vaccine adjuvant activity of LT-IIa-B (Rodriguez-Jimenez et al, 2003), derived from enterotoxin, and Chlamydia major OmpA have both been linked to TLR2 activation (Cheng et al, 2011; Lee et al, 2011). Not all studies have shown enhanced adaptive immune responses with TLR2 agonists, however, as these molecules sometimes lead to high induction of IL-10 and potential downregulation of immune responses in certain circumstances (Netea et al, 2004).…”