Induction of protective immunity by vaccination against Chlamydia trachomatis using the major outer membrane protein adjuvanted with CpG oligodeoxynucleotide coupled to the nontoxic B subunit of cholera toxin

Abstract

The present study was undertaken to test the efficacy of immunization with the native major outer membrane protein (nMOMP) of C. trachomatis mouse pneumonitis (MoPn) serovar in combination with a novel immunostimulatory adjuvant consisting of CpG oligodeoxynucleotide (ODN) linked to the nontoxic B subunit of cholera toxin (CTB-CpG) to elicit a protective immune response to C. trachomatis. High levels of Chlamydia specific IgG antibodies were detected in the sera from BALB/c mice immunized intramuscularly and subcutaneously (i.m.+s.c.) with the nMOMP/CTB-CpG vaccine or with nMOMP adjuvanted with a mixture of CT and CpG ODN (CT + CpG). Further, these immunization schemes gave rise to significant T-cell mediated Chlamydia-specific immune responses. No Chlamydia-specific humoral or cell-mediated immune responses were detected in the control mice vaccinated with ovalbumin together with either CTB-CpG or CT + CpG. Following an intranasal challenge with C. trachomatis the groups of mice immunized with nMOMP plus CTB-CpG, CT + CpG or live C. trachomatis were found to be protected based on their change in body weight and lung weight as well as number of inclusion forming unit recovered from the lungs, as compared with control groups immunized with ovalbumin plus either adjuvants. Interestingly, IFN-γ-producing CD4+, but not CD8+, T-cells showed a significant correlation with the outcomes of the challenge. In conclusion, nMOMP in combination with the novel adjuvant CTB-CpG elicited a significant antigen specific antibody and cell-mediated immune responses as well as protection against a pulmonary challenge with C. trachomatis.

Selection of Adjuvants for Enhanced Vaccine Potency

“…Successful examples include fusion of subunit B of LT to a viral protein [287], conjugation of toxoids to capsular polysaccharides of many invasive bacteria such as Streptococcus pneumoniae, H. influenzae type b, meningococci, pneumococci [2,288,289], and conjugation of LT subunits with CpG [111,290]. It should be noted that the bacterial toxins can initiate a strong humoral immune response, which may overshadow the response to the conjugate antigen [7].…”

Chlamydia trachomatis recombinant MOMP encapsulated in PLGA nanoparticles triggers primarily T helper 1 cellular and antibody immune responses in mice: a desirable candidate nanovaccine

“…Second-generation vaccines are subunit immunogens, such as proteins, DNA, RNA, or oligonucleotides, and have been shown to be very promising. [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] However, these secondgeneration vaccines need effective delivery systems to protect their respective immunogens from rapid degradation and to potentiate immunological responses. Biodegradable nanoparticles used as immune potentiators and delivery systems are now playing an increasing role in next-generation vaccine development projects.…”

“…26,27 Nonetheless, vaccine research with MOMP as the prime immunogen has been both encouraging and disappointing. Previous studies using native MOMP in combination with adjuvant revealed some protective efficacy in vivo, [28][29][30] but the drawback with native MOMP is the expense associated with its production if selected as a candidate vaccine. 16 The use of recombinant MOMP (rMOMP) with conventional adjuvants, including cholera toxin, aluminum, and CpG, to name a few, has been widely explored, but the degree of protection achieved with these vaccines is not as robust as that achieved with native MOMP.…”

REVIEW ARTICLE: Chlamydia trachomatis, a Hidden Epidemic: Effects on Female Reproduction and Options for Treatment

“…The use of the major outer membrane protein (MOMP) as a vaccine candidate has been extensively studied, with varying success. [72][73][74][75][76][77][78][79] The use of this antigen has resulted from the fact that it constitutes approximately 60% of the outer membrane protein mass of the chlamydial EB. 47 However, MOMP contains four variable domains that are surface exposed and are antigenically variable between serovars.…”