Biomedical Scientist Lawrence Livermore National Laboratory Livermore, California, United States
Background:
The successful development of mRNA-based vaccines against SARS-CoV-2 underscores the transformative potential of this formulation modality in rapidly developing and disseminating protective vaccines. While the implementation of mRNA-based vaccines against viral pathogens has advanced exponentially over the past 3 years, mRNA-based vaccines against bacterial pathogens remain underdeveloped. Our goal is to leverage mRNA technology to elicit protective immunological responses against Chlamydia.
Methods:
To evaluate the potential of mRNA-based vaccines against Chlamydia, we engineered mRNA constructs encoding two protective Chlamydia antigens: the major outer membrane protein (MOMP) and the chlamydial protease-like activity factor (CPAF) from Chlamydia muridarum. Three antigenic constructs were evaluated: 1) full-length MOMP, 2) a polypeptide comprised of multiple MOMP T- and B-cell epitopes, and 3) full-length inactivated CPAF. These antigens were encoded in self-amplifying mRNAs (SAM), which are derived from an alphavirus genome that can self-amplify in the cytoplasm upon cellular entry to produce high copy numbers of antigen-encoding mRNA at low SAM doses (relative to non-replicating mRNAs). The SAMs were subsequently formulated into lipid nanoparticles (LNPs) and administered intramuscularly using a prime-boost regimen to BALB/c mice.
Results:
Preliminary data suggest that the Chlamydia antigens can elicit significant humoral responses, as measured by serum IgG titers. Evaluation of T-cell responses and protective efficacy studies are currently underway.
Conclusion:
Our data suggest that mRNA-based antigens represent promising candidates for Chlamydia vaccines and merit additional optimization of antigen constructs, LNP formulation, and dosing regimen to further enhance antigen-specific immune responses.
