Vaccination with major outer membrane protein proteosomes elicits protection in mice against a Chlamydia respiratory
Delia F Tifrea1, Sukumar Pal, Deana N Toussi
1Department of Pathology and Laboratory Medicine, Medical Sciences I, Room D440, University of California, Irvine, Irvine, CA 92697-4800, USA.
Abstract:
Vaccines formulated with the Chlamydia muridarum native major outer membrane protein (nMOMP) have so far been shown to elicit the most robust protection against this pathogen. nMOMP is a membrane protein and therefore, detergents are used to keep it in solution. Detergents however, have toxic effects. To address this limitation, we tested a nMOMP proteosome vaccine and compared its ability to elicit protection against nMOMP solubilized in the detergent Z3-14. The two preparations were formulated with or without CpG + Montanide (C/M). As a control antigen we used ovalbumin. Mice vaccinated with nMOMP developed strong humoral and cell mediated Chlamydia-specific immune responses. Based on the IgG2a/IgG1 levels in serum and amounts of IFN-γ in splenocytes supernatants the immune responses were predominantly Th1-biased. The animals were subsequently challenged intranasally with 2 × 10(3)Chlamydia inclusion forming units (IFU) and the course of the infection was followed for 10 days when the mice were euthanized. Based on changes in body weight, weight of the lungs and number of IFU recovered from the lungs, mice immunized with nMOMP-Ps and nMOMP + Z3-14 adjuvanted with C/M showed the most robust protection. In summary, nMOMP-Ps should be considered as Chlamydia vaccine candidates.
Insights
A novel Chlamydia muridarum vaccine using native major outer membrane protein (nMOMP) proteosomes demonstrated robust protection. This approach avoids toxic detergents, offering a promising alternative for Chlamydia vaccine development.
Area of Science:
- Immunology
- Vaccinology
- Microbiology
Background:
- Chlamydia muridarum infections pose a significant health challenge.
- Vaccines targeting the native major outer membrane protein (nMOMP) show promise for protection.
- Detergents used to solubilize nMOMP have toxic effects, necessitating alternative vaccine formulations.
Purpose of the Study:
- To evaluate a Chlamydia muridarum nMOMP proteosome vaccine candidate.
- To compare the efficacy of nMOMP proteosomes against detergent-solubilized nMOMP.
- To assess the immunogenicity and protective capabilities of these vaccine formulations.
Main Methods:
- Mice were vaccinated with either nMOMP proteosomes (nMOMP-Ps) or nMOMP solubilized in Z3-14 detergent.
- Vaccines were formulated with or without CpG + Montanide (C/M) adjuvants.
- Immune responses (humoral and cell-mediated) were analyzed, and mice were challenged intranasally with C. muridarum.
Main Results:
- nMOMP vaccination induced strong, Th1-biased humoral and cell-mediated immune responses.
- Both nMOMP-Ps and nMOMP + Z3-14 adjuvanted with C/M provided robust protection against C. muridarum challenge.
- Protection was assessed by body weight changes, lung weight, and reduction in Chlamydia inclusion-forming units (IFU).
Conclusions:
- nMOMP proteosomes (nMOMP-Ps) represent a viable and potentially safer vaccine candidate against Chlamydia muridarum.
- Adjuvant formulation with CpG + Montanide enhances protective immunity.
- This study highlights the potential of proteosome-based vaccines for infectious diseases.
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