Orally Administrated Recombinant Vaccinia Virus Displaying ROP4 Induces Protection against Toxoplasma gondii Challenge Infection.

Keon-Woong Yoon,Fu-Shi Quan,Min-Ju Kim,Gi-Deok Eom,Hae-Ji Kang,Ki-Back Chu

doi:10.3390/vaccines10020152

Keon-Woong Yoon, Fu-Shi Quan + Show 4 more

Open Access

https://doi.org/10.3390/vaccines10020152

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Abstract

Recombinant vaccinia viruses (rVVs) are attenuated viruses and are widely utilized as vectored vaccine platforms against numerous diseases. However, the protective efficacy of these rVV vaccines against Toxoplasma gondii and the resulting mucosal immunity has not been thoroughly assessed. Here, rVVs expressing the rhoptry protein 4 (ROP4) of T. gondii were generated. To evaluate the protection induced by the vaccines, mice were orally immunized with the ROP4-rVVs and subsequently challenge-infected with a lethal dose of T. gondii ME49 strain. Immunization with the rVVs induced higher levels of parasite-specific IgG and IgA antibody responses in sera compared to unimmunized control (NC). Upon challenge infection, significantly higher levels of IgG or IgA antibody responses in the brain, intestines, and vaginal samples were found in the immunized mice compared to NC. The ROP4-rVV vaccination elicited potent IgG and IgA secreting cell (ASC) responses, while substantially enhancing germinal center B cell, as well as CD4+ and CD8+ T cell responses from lymphoid organs. The production of pro-inflammatory cytokines IFN-γ and IL-6 in the brains was markedly diminished following immunization. The immunized mice also experienced reduced bodyweight loss and possessed fewer brain cysts than the control group. These results suggest that oral delivery of ROP4 displaying rVVs induced mucosal and systemic immunities that contributed to protection against lethal T. gondii challenge infection.

Highlights

Infection in humans can occur through the ingestion of undercooked meat and contaminated water, resulting in severe symptoms depending on the host’s immune status
We have recently investigated the efficacy of rhoptry protein 4 (ROP4)-expressing recombinant baculovirus vaccines and the resulting immune responses in mice [10]
Our findings demonstrated that the ROP4-Recombinant vaccinia viruses (rVVs) vaccines elicited a robust cellular and humoral response that protected mice upon lethal T. gondii infection

Summary

Introduction

Infection in humans can occur through the ingestion of undercooked meat and contaminated water, resulting in severe symptoms depending on the host’s immune status. The current treatment options for T. gondii infection involve co-administration of pyrimethamine and sulfadiazine. Other drugs such as hydroxynaphthoquinone (atovaquone) and azithromycin could be used, but there are major issues with these drugs. Pathogen drug resistance is a recurring theme frequently reported from various diseases and toxoplasmosis is no exception. This and the severe side effects, poor patient tolerability, and therapeutic ineffectiveness against bradyzoites of T. gondii are several of the obstacles that must be surmounted [1]. Vaccines are widely considered to be the most cost-effective healthcare intervention, and successful vaccines can benefit public health, which translates to economic growth [2]. For these reasons, developing a vaccine to protect against toxoplasmosis is an urgent need

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