Encapsulation of Recombinant MOMP in Extended-Releasing PLGA 85:15 Nanoparticles Confer Protective Immunity Against a Chlamydia muridarum Genital Challenge and Re-Challenge

• Published in: Frontiers in immunology Vol. 12; p. 660932
• Main Authors: Sahu, Rajnish, Dixit, Saurabh, Verma, Richa, Duncan, Skyla A, Smith, Lula, Giambartolomei, Guillermo H, Singh, Shree R, Dennis, Vida A
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 14-04-2021
• Subjects: Adjuvants, Immunologic; Animals; Antibodies, Bacterial - blood; Antimicrobial Cationic Peptides - administration & dosage; Antimicrobial Cationic Peptides - chemistry; Antimicrobial Cationic Peptides - metabolism; Bacterial Outer Membrane Proteins - administration & dosage; Bacterial Outer Membrane Proteins - genetics; Bacterial Outer Membrane Proteins - immunology; Bacterial Vaccines - administration & dosage; Bacterial Vaccines - immunology; Chlamydia Infections - prevention & control; Chlamydia muridarum; Chlamydia muridarum - drug effects; Cytokines - immunology; Delayed-Action Preparations - administration & dosage; Female; Genitalia - drug effects; Genitalia - microbiology; Immunology; major outer membrane protein; Mice; Mice, Inbred BALB C; Nanoparticles - administration & dosage; Nanoparticles - chemistry; nanovaccine; neutralizing antibodies; PLGA nanoparticles; Recombinant Proteins - administration & dosage; Recombinant Proteins - genetics; Recombinant Proteins - immunology; Vaccination; nanovaccine; neutralizing antibodies; major outer membrane protein; PLGA nanoparticles; Chlamydia muridarum
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.660932

Recently we reported the immune-potentiating capacity of a
nanovaccine (PLGA-rMOMP) comprising rMOMP (recombinant major outer membrane protein) encapsulated in extended-releasing PLGA [poly (D, L-lactide-co-glycolide) (85:15)] nanoparticles. Here we hypothesized that PLGA-rMOMP would bolster immune-effector mechanisms to confer protective efficacy in mice against a
genital challenge and re-challenge. Female BALB/c mice received three immunizations, either subcutaneously (SC) or intranasally (IN), before receiving an intravaginal challenge with
on day 49 and a re-challenge on day 170. Both the SC and IN immunization routes protected mice against genital challenge with enhanced protection after a re-challenge, especially in the SC mice. The nanovaccine induced robust antigen-specific Th1 (IFN-γ, IL-2) and IL-17 cytokines plus CD4
proliferating T-cells and memory (CD44
CD62L
) and effector (CD44
CD62L
) phenotypes in immunized mice. Parallel induction of antigen-specific systemic and mucosal Th1 (IgG2a, IgG2b), Th2 (IgG1), and IgA antibodies were also noted. Importantly, immunized mice produced highly functional Th1 avidity and serum antibodies that neutralized
infectivity of McCoy fibroblasts
that correlated with their respective protection levels. The SC, rather than the IN immunization route, triggered higher cellular and humoral immune effectors that improved mice protection against genital
We report for the first time that the extended-releasing PLGA 85:15 encapsulated rMOMP nanovaccine confers protective immunity in mice against genital
and advances the potential towards acquiring a nano-based
vaccine.