RecNcMIC3-1-R is a microneme- and rhoptry-based chimeric antigen that protects against acute neosporosis and limits cerebral parasite load in the mouse model for Neospora caninum infection

Monney, Thierry; Rütti, David; Schorer, Michelle; Debache, Karim; Grandgirard, Denis; Leib, Stephen L.; Hemphill, Andrew (2011). RecNcMIC3-1-R is a microneme- and rhoptry-based chimeric antigen that protects against acute neosporosis and limits cerebral parasite load in the mouse model for Neospora caninum infection. Vaccine, 29(40), pp. 6967-6975. Amsterdam: Elsevier 10.1016/j.vaccine.2011.07.038

[img] Text
1-s2.0-S0264410X1101070X-main.pdf__tid=4cebb85e-24e1-11e5-b195-00000aab0f27&acdnat=1436298758_604a4497f4c3468a370db8259c6d9167 - Published Version
Restricted to registered users only
Available under License Publisher holds Copyright.

Download (822kB) | Request a copy

In order to achieve host cell entry, the apicomplexan parasite Neospora caninum relies on the contents of distinct organelles, named micronemes, rhoptries and dense granules, which are secreted at defined timepoints during and after host cell entry. It was shown previously that a vaccine composed of a mixture of three recombinant antigens, corresponding to the two microneme antigens NcMIC1 and NcMIC3 and the rhoptry protein NcROP2, prevented disease and limited cerebral infection and transplacental transmission in mice. In this study, we selected predicted immunogenic domains of each of these proteins and created four different chimeric antigens, with the respective domains incorporated into these chimers in different orders. Following vaccination, mice were challenged intraperitoneally with 2 × 10(6)N. caninum tachzyoites and were then carefully monitored for clinical symptoms during 4 weeks post-infection. Of the four chimeric antigens, only recNcMIC3-1-R provided complete protection against disease with 100% survivors, compared to 40-80% of survivors in the other groups. Serology did not show any clear differences in total IgG, IgG1 and IgG2a levels between the different treatment groups. Vaccination with all four chimeric variants generated an IL-4 biased cytokine expression, which then shifted to an IFN-γ-dominated response following experimental infection. Sera of recNcMIC3-1-R vaccinated mice reacted with each individual recombinant antigen, as well as with three distinct bands in Neospora extracts with similar Mr as NcMIC1, NcMIC3 and NcROP2, and exhibited distinct apical labeling in tachyzoites. These results suggest that recNcMIC3-1-R is an interesting chimeric vaccine candidate and should be followed up in subsequent studies in a fetal infection model.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Parasitology
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases > Research
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases

UniBE Contributor:

Monney, Thierry; Schorer, Michelle; Debache, Karim; Grandgirard, Denis; Leib, Stephen and Hemphill, Andrew

ISSN:

0264-410X

Publisher:

Elsevier

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:24

Last Modified:

22 Jul 2015 10:17

Publisher DOI:

10.1016/j.vaccine.2011.07.038

PubMed ID:

21787824

Web of Science ID:

000295300500019

BORIS DOI:

10.7892/boris.8285

URI:

https://boris.unibe.ch/id/eprint/8285 (FactScience: 213802)

Actions (login required)

Edit item Edit item
Provide Feedback