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Published on: July 25, 2022
A Recombinant 47-kDa Outer Membrane Protein Induces an Immune Response against Orientia tsutsugamushi Strain Boryong
Sangho Choi1, Hang Jin Jeong1, Kyu-Jam Hwang1
1Division of Zoonoses, Center for Immunology and Pathology, National Institute of Health, Korea Centers for Disease Control and Prevention, Cheongju, Korea.
Abstract:
We investigated the 47-kDa outer membrane protein (OMP), which is a periplasmic serine protease and an antigenic major surface protein of Orientia tsutsugamushi, as a vaccine candidate. We developed a conventional subunit vaccine expressing recombinant 47-kDa OMP (rec47) and a DNA vaccine (p47). In mouse immunization experiments, intranasal immunization with rec47 alone or with rec47 plus heat-labile enterotoxin B subunit from Escherichia coli or plus cholera toxin (CT) as adjuvants induced a higher amount of rec47-specific antibodies than intramuscular immunization with p47 alone or with p47 plus pBOOST2-samIRF7/3 (pB) as adjuvant. Moreover, the combination of rec47 and CT induced a strong cellular immune response to 47-kDa OMP, as demonstrated by a spleen cell proliferation assay, and also induced Th1- and Th2-type cytokine production, as demonstrated by a cytokine enzyme-linked immunosorbent assay. Intranasal immunization with rec47 plus CT was the most effective method for the induction of humoral and cell-mediated immune responses. Furthermore, relatively strong protection against homologous O. tsutsugamushi strain Boryong challenge was observed in mice immunized with rec47 plus CT. Therefore, 47-kDa OMP is an attractive candidate for developing a prophylactic vaccine against scrub typhus by O. tsutsugamushi infection.
Insights
The 47-kDa outer membrane protein (OMP) of Orientia tsutsugamushi shows promise as a vaccine candidate. Intranasal immunization with recombinant 47-kDa OMP and cholera toxin (CT) effectively induced immune responses and offered protection against scrub typhus.
Area of Science:
- Immunology
- Vaccinology
- Microbiology
Background:
- Orientia tsutsugamushi causes scrub typhus, a significant public health concern.
- The 47-kDa outer membrane protein (OMP) is a major surface antigen of O. tsutsugamushi and a potential vaccine target.
Purpose of the Study:
- To evaluate the 47-kDa OMP as a vaccine candidate against O. tsutsugamushi.
- To compare the immunogenicity and efficacy of subunit and DNA vaccines with different adjuvants and administration routes.
Main Methods:
- Development of a recombinant subunit vaccine (rec47) and a DNA vaccine (p47).
- Mouse immunization via intranasal and intramuscular routes with various adjuvants (heat-labile enterotoxin B subunit, cholera toxin, pBOOST2-samIRF7/3).
- Assessment of humoral immunity (antibody levels), cellular immunity (spleen cell proliferation), cytokine production (Th1/Th2 response), and protection against O. tsutsugamushi challenge.
Main Results:
- Intranasal immunization with rec47 plus cholera toxin (CT) induced higher levels of rec47-specific antibodies compared to other methods.
- This combination also elicited a strong cellular immune response, Th1/Th2 cytokine production, and significant protection against homologous O. tsutsugamushi challenge.
- Intramuscular immunization with p47 showed lower immunogenicity.
Conclusions:
- The 47-kDa OMP is a promising candidate for a prophylactic vaccine against scrub typhus.
- Intranasal administration of recombinant 47-kDa OMP with CT as an adjuvant is the most effective strategy for inducing protective immunity.
