Use of a Th1 Stimulator Adjuvant for Vaccination against Neospora caninum Infection in the Pregnant Mouse Model.

Thierry Monney,Andrew Hemphill,Stephen Leib,Denis Grandgirard

doi:10.3390/pathogens2020193

Thierry Monney, Andrew Hemphill + Show 2 more

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https://doi.org/10.3390/pathogens2020193

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Abstract

Vertical transmission from an infected cow to its fetus accounts for the vast majority of new Neospora caninum infections in cattle. A vaccine composed of a chimeric antigen named recNcMIC3-1-R, based on predicted immunogenic domains of the two microneme proteins NcMIC1 and NcMIC3, the rhoptry protein NcROP2, and emulsified in saponin adjuvants, significantly reduced the cerebral infection in non-pregnant BALB/c mice. Protection was associated with a mixed Th1/Th2-type cytokine response. However, the same vaccine formulation elicited a Th2-type immune response in pregnant mice and did not prevent vertical transmission or disease, neither in dams nor in offspring mice. In this study, an alternative vaccine formulation containing recNcMIC3-1-R emulsified in Freund’s incomplete adjuvant, a stimulator of the cellular immunity, was investigated. No protection against vertical transmission and cerebral infection in the pregnant mice and a very limited protective effect in the non-pregnant mice were observed. The vaccine induced a Th1-type immune response characterized by high IgG2a titres and strong IFN-γ expression, which appeared detrimental to pregnancy.

Highlights

Neospora caninum is an intracellular apicomplexan parasite, which is reported as a major cause of bovine abortion worldwide, and neosporosis represents an important veterinary disease of high economic significance [1,2,3]
Vaccination with a recombinant chimeric antigen composed of putative immunogenic domains of the three proteins predicted in silico and emulsified in saponin adjuvants conferred a high level of protection against cerebral infection in non-pregnant mice [24], but did not prevent vertical transmission, nor cerebral infection in pregnant mice [25]
Comparison of antibody responses and cytokine data in pregnant and non-pregnant mouse models showed that a mixed Th1-/Th2-type immune response was associated with the protection observed in the non-pregnant mouse model, but a Th2-biased immune response was observed in the pregnant mice [24]

Summary

Introduction

Neospora caninum is an intracellular apicomplexan parasite, which is reported as a major cause of bovine abortion worldwide, and neosporosis represents an important veterinary disease of high economic significance [1,2,3]. Studies employing different recombinant protein vaccine candidates have shown promising results in terms of limiting the parasite load and reducing the effects of the disease (reviewed in [15]). Vaccination with a recombinant chimeric antigen composed of putative immunogenic domains of the three proteins (recNcMIC3-1-R) predicted in silico and emulsified in saponin adjuvants conferred a high level of protection against cerebral infection in non-pregnant mice [24], but did not prevent vertical transmission, nor cerebral infection in pregnant mice [25]. The use of an adjuvant that stimulates the cellular immunity, in order to counterbalance the inherent Th2-type biased immune response observed in the pregnant mice, may lead to protection. We report on the use of recNcMIC3-1-R emulsified in Freund’s incomplete adjuvant (FIA) for vaccination in the pregnant mouse model

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