Intranasal Immunization With Nanoparticles Containing an Orientia tsutsugamushi Protein Vaccine Candidate and a Polysorbitol Transporter Adjuvant Enhances Both Humoral and Cellular Immune Responses

Cheol Gyun Kim; Won Kyong Kim; Narae Kim; Young Jin Pyung; Da-Jeong Park; Jeong-Cheol Lee; Chong-Su Cho; Hyuk Chu; Cheol-Heui Yun

doi:10.4110/in.2023.23.e47

Intranasal Immunization With Nanoparticles Containing an Orientia tsutsugamushi Protein Vaccine Candidate and a Polysorbitol Transporter Adjuvant Enhances Both Humoral and Cellular Immune Responses

Immune Netw. 2023 Dec 15;23(6):e47. doi: 10.4110/in.2023.23.e47. eCollection 2023 Dec.

Authors

Cheol Gyun Kim^{1

2}, Won Kyong Kim³, Narae Kim¹, Young Jin Pyung¹, Da-Jeong Park¹, Jeong-Cheol Lee¹, Chong-Su Cho¹, Hyuk Chu³, Cheol-Heui Yun^{1

4

5

6}

Affiliations

¹ Department of Agricultural Biotechnology, and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Korea.
² Bio-MAX/N-Bio, Seoul National University, Seoul 08826, Korea.
³ Division of Zoonotic and Vector Borne Disease Research, Center for Infectious Disease Research, National Institute of Health, Cheongju 28159, Korea.
⁴ Center for Food and Bioconvergence, Seoul National University, Seoul 08826, Korea.
⁵ Institutes of Green-bio Science and Technology, Seoul National University, Pyeongchang 25354, Korea.
⁶ Interdisciplinary Programs in Agricultural Genomics, Seoul National University, Seoul 08826, Korea.

Abstract

Scrub typhus, a mite-borne infectious disease, is caused by Orientia tsutsugamushi. Despite many attempts to develop a protective strategy, an effective preventive vaccine has not been developed. The identification of appropriate Ags that cover diverse antigenic strains and provide long-lasting immunity is a fundamental challenge in the development of a scrub typhus vaccine. We investigated whether this limitation could be overcome by harnessing the nanoparticle-forming polysorbitol transporter (PST) for an O. tsutsugamushi vaccine strategy. Two target proteins, 56-kDa type-specific Ag (TSA56) and surface cell Ag A (ScaA) were used as vaccine candidates. PST formed stable nano-size complexes with TSA56 (TSA56-PST) and ScaA (ScaA-PST); neither exhibited cytotoxicity. The formation of Ag-specific IgG2a, IgG2b, and IgA in mice was enhanced by intranasal vaccination with TSA56-PST or ScaA-PST. The vaccines containing PST induced Ag-specific proliferation of CD8⁺ and CD4⁺ T cells. Furthermore, the vaccines containing PST improved the mouse survival against O. tsutsugamushi infection. Collectively, the present study indicated that PST could enhance both Ag-specific humoral immunity and T cell response, which are essential to effectively confer protective immunity against O. tsutsugamushi infection. These findings suggest that PST has potential for use in an intranasal vaccination strategy.

Keywords: Adaptive immunity; Intranasal administration; Nano-vaccine; Orientia tsutsugamushi.