Vaccination with Recombinant Microneme Proteins Confers Protection against Experimental Toxoplasmosis in Mice
Author(s)
Type
Journal Article
Abstract
Toxoplasmosis, a zoonotic disease caused by Toxoplasma gondii, is an important public
health problem and veterinary concern. Although there is no vaccine for human toxoplasmosis,
many attempts have been made to develop one. Promising vaccine candidates utilize
proteins, or their genes, from microneme organelle of T. gondii that are involved in the
initial stages of host cell invasion by the parasite. In the present study, we used different
recombinant microneme proteins (TgMIC1, TgMIC4, or TgMIC6) or combinations of these
proteins (TgMIC1-4 and TgMIC1-4-6) to evaluate the immune response and protection
against experimental toxoplasmosis in C57BL/6 mice. Vaccination with recombinant
TgMIC1, TgMIC4, or TgMIC6 alone conferred partial protection, as demonstrated by
reduced brain cyst burden and mortality rates after challenge. Immunization with TgMIC1-4
or TgMIC1-4-6 vaccines provided the most effective protection, since 70% and 80% of
mice, respectively, survived to the acute phase of infection. In addition, these vaccinated
mice, in comparison to non-vaccinated ones, showed reduced parasite burden by 59% and
68%, respectively. The protective effect was related to the cellular and humoral immune
responses induced by vaccination and included the release of Th1 cytokines IFN-γ and IL-
12, antigen-stimulated spleen cell proliferation, and production of antigen-specific serum
antibodies. Our results demonstrate that microneme proteins are potential vaccines against
T. gondii, since their inoculation prevents or decreases the deleterious effects of the
infection.
health problem and veterinary concern. Although there is no vaccine for human toxoplasmosis,
many attempts have been made to develop one. Promising vaccine candidates utilize
proteins, or their genes, from microneme organelle of T. gondii that are involved in the
initial stages of host cell invasion by the parasite. In the present study, we used different
recombinant microneme proteins (TgMIC1, TgMIC4, or TgMIC6) or combinations of these
proteins (TgMIC1-4 and TgMIC1-4-6) to evaluate the immune response and protection
against experimental toxoplasmosis in C57BL/6 mice. Vaccination with recombinant
TgMIC1, TgMIC4, or TgMIC6 alone conferred partial protection, as demonstrated by
reduced brain cyst burden and mortality rates after challenge. Immunization with TgMIC1-4
or TgMIC1-4-6 vaccines provided the most effective protection, since 70% and 80% of
mice, respectively, survived to the acute phase of infection. In addition, these vaccinated
mice, in comparison to non-vaccinated ones, showed reduced parasite burden by 59% and
68%, respectively. The protective effect was related to the cellular and humoral immune
responses induced by vaccination and included the release of Th1 cytokines IFN-γ and IL-
12, antigen-stimulated spleen cell proliferation, and production of antigen-specific serum
antibodies. Our results demonstrate that microneme proteins are potential vaccines against
T. gondii, since their inoculation prevents or decreases the deleterious effects of the
infection.
Date Issued
2015-11-17
Date Acceptance
2015-10-04
Citation
PLOS One, 2015, 10 (11)
ISSN
1932-6203
Publisher
Public Library of Science
Journal / Book Title
PLOS One
Volume
10
Issue
11
Copyright Statement
© 2015 Pinzan et al. This is an open
access article distributed under the terms of the
Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any
medium, provided the original author and source are
credited.
access article distributed under the terms of the
Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any
medium, provided the original author and source are
credited.
License URL
Sponsor
Medical Research Council (MRC)
Grant Number
G0800038
Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
CELL-MEDIATED-IMMUNITY
APICOMPLEXAN PARASITES
GONDII INFECTION
IFN-GAMMA
PERORAL INFECTION
TNF-ALPHA
INVASION
RESISTANCE
RECOGNITION
RESPONSES
Publication Status
Published
Article Number
e0143087