Evaluation of CpG-ODN-Adjuvanted Toxoplasma Gondii Virus-Like Particle Vaccine upon One, Two, and Three Immunizations.

Hae-Ji Kang,Hyunwoo Park,Hui Jin,Fu-Shi Quan,Su-Hwa Lee,Ki-Back Chu,Min-Ju Kim,Eun-Kyung Moon

doi:10.3390/pharmaceutics12100989

Hae-Ji Kang, Hyunwoo Park + Show 6 more

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https://doi.org/10.3390/pharmaceutics12100989

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Abstract

Successful vaccines against specific pathogens often require multiple immunizations and adjuvant usage. Yet, assessing the protective efficacy of different immunization regimens with adjuvanted Toxoplasma gondii vaccines remains elusive. In this study, we investigated the vaccine efficacy induced by CpG-ODN-adjuvanted T. gondii virus-like particles (VLPs) after challenge infection with T. gondii (ME49) in mice (BALB/c) upon one, two, and three immunizations. Immunization with adjuvanted T. gondii VLPs induced higher levels of T. gondii-specific IgG and/or IgA antibody responses, germinal center (GC) B cells, total B cells, and CD4+ and CD8+ T cells compared with unadjuvanted VLPs. Increasing the number of immunizations was strongly correlated with enhanced protective immunity against T. gondii in mice, with the highest protection being demonstrated in mice thrice-immunized with either adjuvanted T. gondii VLPs or VLPs alone. Notably, lesser bodyweight reductions and cerebral cyst counts were observed in mice receiving multiple immunizations with the adjuvanted VLPs, thereby confirming the effectiveness of adjuvanted boost immunizations. These results demonstrated that multiple immunizations with T. gondii VLPs is an effective approach, and the CpG-ODN can be developed as an effective adjuvant for T. gondii VLP vaccines.

Highlights

Toxoplasma gondii is an obligate intracellular parasite widely distributed across the globe and infects a vast array of mammals including humans [1,2,3]
All of the mice immunized with the DNA vaccine encoding the T. gondii surface antigen 1 (SAG1) survived upon T. gondii (ME49) challenge infection [10], whereas none of the mice immunized with the DNA vaccine expressing T. gondii superoxide dismutase (SOD) survived [11]
To determine whether the CpG-ODN adjuvant can enhance the efficacy of the T. gondii virus-like particles (VLPs) vaccine after multiple immunizations, mice were immunized with either T. gondii VLPs alone or CpG-ODN-adjuvanted T. gondii VLPs for one, two, or three times

Summary

Introduction

Toxoplasma gondii is an obligate intracellular parasite widely distributed across the globe and infects a vast array of mammals including humans [1,2,3]. While therapeutic interventions are possible, their applications are hindered by toxicity and other side effects [7,8] To address these limitations, multitudes of T. gondii vaccine studies are currently being conducted using DNA, protein subunit, inactivated, and attenuated vaccines to develop an effective toxoplasmosis vaccine [9]. Survival discrepancies were observed from mice immunized with various subunit vaccines before challenge infection with T. gondii ME49 [12,13,14]. In contrast to the DNA or recombinant subunit vaccines, immunizing the mice with attenuated T. gondii ensured that all of the immunized mice survived following challenge infection with a lethal dose of ME49 [15,16]. All of the immunized mice survived in our previous studies, incomplete removal of cerebral cysts and bodyweight loss upon challenge infection from these mice indicated that further improvements to the VLP vaccines are needed to minimize disease manifestation

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