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Cell-Free Scaled Production and Adjuvant Addition to a Recombinant Major Outer Membrane Protein from Chlamydia muridarum for Vaccine Development
Published on: March 16, 2022
Chlamydia trachomatis native major outer membrane protein induces partial protection in nonhuman primates:
Laszlo Kari1, William M Whitmire, Deborah D Crane
1Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
Abstract:
A vaccine is likely the most effective strategy for controlling human chlamydial infections. Recent studies have shown immunization with Chlamydia muridarum major outer membrane protein (MOMP) can induce significant protection against infection and disease in mice if its native trimeric structure is preserved (nMOMP). The objective of this study was to investigate the immunogenicity and vaccine efficacy of Chlamydia trachomatis nMOMP in a nonhuman primate trachoma model. Cynomolgus monkeys (Macaca fascicularis) were immunized systemically with nMOMP, and monkeys were challenged ocularly. Immunization induced high serum IgG and IgA ELISA Ab titers, with Abs displaying high strain-specific neutralizing activity. The PBMCs of immunized monkeys produced a broadly cross-reactive, Ag-specific IFN-gamma response equivalent to that induced by experimental infection. Immunized monkeys exhibited a significant decrease in infectious burden during the early peak shedding periods (days 3-14). However, at later time points, they exhibited no difference from control animals in either burden or duration of infection. Immunization had no effect on the progression of ocular disease. These results show that systemically administered nMOMP is highly immunogenic in nonhuman primates and elicits partially protective immunity against ocular chlamydial challenge. This is the first time a subunit vaccine has shown a significant reduction in ocular shedding in nonhuman primates. A partially protective vaccine, particularly one that reduces infectious burden after primary infection of children, could interrupt the natural trachoma reinfection cycle. This would have a beneficial effect on the transmission between children and sensitized adults which drives blinding inflammatory disease.
Insights
A novel vaccine using native trimeric major outer membrane protein (nMOMP) from Chlamydia trachomatis showed partial protection against ocular infection in nonhuman primates. This vaccine significantly reduced early infectious burden, offering hope for interrupting trachoma transmission cycles.
Area of Science:
- Ophthalmology
- Vaccinology
- Microbiology
Background:
- Chlamydial infections, particularly trachoma, pose a significant global health burden.
- Effective vaccines are crucial for controlling human chlamydial infections.
- Previous studies in mice demonstrated protection using native trimeric major outer membrane protein (nMOMP).
Purpose of the Study:
- To assess the immunogenicity and vaccine efficacy of Chlamydia trachomatis nMOMP in a nonhuman primate trachoma model.
- To evaluate the immune responses and protective effects of nMOMP immunization against ocular chlamydial challenge.
Main Methods:
- Cynomolgus monkeys were immunized systemically with nMOMP.
- Immunized and control monkeys were challenged ocularly with Chlamydia trachomatis.
- Serum antibody titers (IgG, IgA), peripheral blood mononuclear cell (PBMC) responses (IFN-gamma), infectious burden, and ocular disease progression were assessed.
Main Results:
- Systemic nMOMP immunization induced high serum IgG and IgA titers with neutralizing activity.
- PBMCs from immunized monkeys showed a broadly cross-reactive, antigen-specific IFN-gamma response.
- Immunized monkeys had a significant reduction in early infectious burden (days 3-14) but no difference at later time points.
- No effect on ocular disease progression was observed.
Conclusions:
- Systemically administered nMOMP is highly immunogenic in nonhuman primates, eliciting partially protective immunity against ocular chlamydial challenge.
- This represents the first subunit vaccine to show significant reduction in ocular shedding in nonhuman primates.
- Partially protective vaccines could interrupt trachoma reinfection cycles, reducing transmission and disease progression.
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