Protective efficacy of vaccination with NcMIC3 and NcMIC8 against Neospora caninum infection in mice

Taotao ZHANG, Xiao ZHANG, Qun LIU, Jianhai XU, Jing LIU

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Front. Agr. Sci. Eng. ›› 2019, Vol. 6 ›› Issue (2) : 188-196. DOI: 10.15302/J-FASE-2019253
RESEARCH ARTICLE
RESEARCH ARTICLE

Protective efficacy of vaccination with NcMIC3 and NcMIC8 against Neospora caninum infection in mice

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Abstract

Microneme proteins (MICs) are important for Apicomplexan parasite invasion due to their adhesion to host cells. Several studies have indicated that Neospora caninum MIC3 and MIC8 are important adhesion factors and potential vaccine candidates against neosporosis. In this study, we evaluated the protective efficacy of recombinant proteins and DNA vaccines of NcMIC3 and NcMIC8. BALB/c mice were immunized with rNcMIC3, rNcMIC8, pcDNA3.1-NcMIC3 and pcDNA3.1-NcMIC8 respectively, and challenged with N. caninum tachyzoites. The immune responses were evaluated through cytokine, antibody measurements and the parasite burden in the mice brain tissues. Serological analysis showed that recombinant protein vaccines induced higher levels of immunoglobulin G (IgG) than other groups. The percentage of IgG1 and IgG2a in the recombinant protein groups was higher than the other groups, and with a predominance of IgG1 over IgG2a, suggesting that recombinant protein vaccines elicited a Th2-type immune response, while DNA vaccines mainly produce a Th1-type immune response. In addition, mice immunized with rNcMIC3 and rNcMIC8 a had lower parasite burden in brain tissue compared with the other groups. These results demonstrate that rNcMIC3 and rNcMIC8 could induce humoral and Th2-type immune response, leading to a considerable level of resistance against neosporosis.

Keywords

NcMIC3 / NcMIC8 / Neospora caninum / vaccination

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Taotao ZHANG, Xiao ZHANG, Qun LIU, Jianhai XU, Jing LIU. Protective efficacy of vaccination with NcMIC3 and NcMIC8 against Neospora caninum infection in mice. Front. Agr. Sci. Eng., 2019, 6(2): 188‒196 https://doi.org/10.15302/J-FASE-2019253

References

[1]
Dubey J P, Schares G, Ortega-Mora L M. Epidemiology and control of neosporosis and Neospora caninum. Clinical Microbiology Reviews, 2007, 20(2): 323–367
CrossRef Pubmed Google scholar
[2]
Mansilla F C, Capozzo A V. Apicomplexan profilins in vaccine development applied to bovine neosporosis. Experimental Parasitology, 2017, 183: 64–68
CrossRef Pubmed Google scholar
[3]
Pereira L M, de Luca G, Abichabki N L M, Bronzon da Costa C M, Yatsuda A P. Synergic in vitro combinations of artemisinin, pyrimethamine and methylene blue against Neospora caninum. Veterinary Parasitology, 2018, 249: 92–97
CrossRef Pubmed Google scholar
[4]
Ma L, Liu G, Liu J, Li M, Zhang H, Tang D, Liu Q. Neospora caninum ROP16 play an important role in the pathogenicity by phosphorylating host cell STAT3. Veterinary Parasitology, 2017, 243: 135–147
CrossRef Pubmed Google scholar
[5]
Nishikawa Y. Towards a preventive strategy for neosporosis: challenges and future perspectives for vaccine development against infection with Neospora caninum. Journal of Veterinary Medical Science, 2017, 79(8): 1374–1380
CrossRef Pubmed Google scholar
[6]
Lv Q, Xing S, Gong P, Chang L, Bian Z, Wang L, Zhang X, Li J. A 78 kDa host cell invasion protein of Neospora caninum as a potential vaccine candidate. Experimental Parasitology, 2015, 148: 56–65
CrossRef Pubmed Google scholar
[7]
Rojo-Montejo S, Collantes-Fernández E, López-Pérez I, Risco-Castillo V, Prenafeta A, Ortega-Mora L M. Evaluation of the protection conferred by a naturally attenuated Neospora caninum isolate against congenital and cerebral neosporosis in mice. Veterinary Research, 2012, 43(1): 62
CrossRef Pubmed Google scholar
[8]
Weston J F, Heuer C, Williamson N B. Efficacy of a Neospora caninum killed tachyzoite vaccine in preventing abortion and vertical transmission in dairy cattle. Preventive Veterinary Medicine, 2012, 103(2–3): 136–144
CrossRef Pubmed Google scholar
[9]
Burleigh B A, Soldati D. Molecular mechanisms of parasite invasion. In: Carruthers V B, Tomley F M, eds. Microneme proteins in Apicomplexans. New York: Landes Bioscience; Springer Science+Business Media, 2008, 47: 33–45
[10]
Debache K, Alaeddine F, Guionaud C, Monney T, Müller J, Strohbusch M, Leib S L, Grandgirard D, Hemphill A. Vaccination with recombinant NcROP2 combined with recombinant NcMIC1 and NcMIC3 reduces cerebral infection and vertical transmission in mice experimentally infected with Neospora caninum tachyzoites. International Journal for Parasitology, 2009, 39(12): 1373–1384
CrossRef Pubmed Google scholar
[11]
Li W, Liu J, Wang J, Fu Y, Nan H, Liu Q. Identification and characterization of a microneme protein (NcMIC6) in Neospora caninum. Parasitology Research, 2015, 114(8): 2893–2902
CrossRef Pubmed Google scholar
[12]
Wang J, Tang D, Li W, Xu J, Liu Q, Liu J. A new microneme protein of Neospora caninum, NcMIC8 is involved in host cell invasion. Experimental Parasitology, 2017, 175: 21–27
CrossRef Pubmed Google scholar
[13]
Lovett J L, Howe D K, Sibley L D. Molecular characterization of a thrombospondin-related anonymous protein homologue in Neospora caninum. Molecular and Biochemical Parasitology, 2000, 107(1): 33–43
CrossRef Pubmed Google scholar
[14]
Cannas A, Naguleswaran A, Müller N, Gottstein B, Hemphill A. Reduced cerebral infection of Neospora caninum-infected mice after vaccination with recombinant microneme protein NcMIC3 and ribi adjuvant. Journal of Parasitology, 2003, 89(1): 44–50
CrossRef Pubmed Google scholar
[15]
Alaeddine F, Keller N, Leepin A, Hemphill A. Reduced infection and protection from clinical signs of cerebral neosporosis in C57BL/6 mice vaccinated with recombinant microneme antigen NcMIC1. Journal of Parasitology, 2005, 91(3): 657–665
CrossRef Pubmed Google scholar
[16]
Yang D, Liu J, Hao P, Wang J, Lei T, Shan D, Liu Q. MIC3, a novel cross-protective antigen expressed in Toxoplasma gondii and Neospora caninum. Parasitology Research, 2015, 114(10): 3791–3799
CrossRef Pubmed Google scholar
[17]
Eperon S, Brönnimann K, Hemphill A, Gottstein B. Susceptibility of B-cell deficient C57BL/6 (microMT) mice to Neospora caninum infection. Parasite Immunology, 1999, 21(5): 225–236
CrossRef Pubmed Google scholar
[18]
Debache K, Guionaud C, Alaeddine F, Mevissen M, Hemphill A. Vaccination of mice with recombinant NcROP2 antigen reduces mortality and cerebral infection in mice infected with Neospora caninum tachyzoites. International Journal for Parasitology, 2008, 38(12): 1455–1463
CrossRef Pubmed Google scholar
[19]
Srinivasan S, Mueller J, Suana A, Hemphill A. Vaccination with microneme protein NcMIC4 increases mortality in mice inoculated with Neospora caninum. Journal of Parasitology, 2007, 93(5): 1046–1055
CrossRef Pubmed Google scholar
[20]
Hao P, Yang N, Cui X, Liu J, Yang D, Liu Q. First isolation of Neospora caninum from blood of a naturally infected adult dairy cow in Beijing, China. Journal of Parasitology, 2014, 100(6): 812–816
CrossRef Pubmed Google scholar
[21]
Monney T, Debache K, Grandgirard D, Leib S L, Hemphill A. Vaccination with the recombinant chimeric antigen recNcMIC3-1-R induces a non-protective Th2-type immune response in the pregnant mouse model for N. caninum infection. Vaccine, 2012, 30(46): 6588–6594
CrossRef Pubmed Google scholar
[22]
Ybañez R H, Leesombun A, Nishimura M, Matsubara R, Kojima M, Sakakibara H, Nagamune K, Nishikawa Y. In vitro and in vivo effects of the phytohormone inhibitor fluridone against Neospora caninum infection. Parasitology International, 2016, 65(4): 319–322
CrossRef Pubmed Google scholar
[23]
Cannas A, Naguleswaran A, Müller N, Eperon S, Gottstein B, Hemphill A. Vaccination of mice against experimental Neospora caninum infection using NcSAG1- and NcSRS2-based recombinant antigens and DNA vaccines. Parasitology, 2003, 126(Pt 4): 303–312
CrossRef Pubmed Google scholar
[24]
Liddell S, Parker C, Vinyard B, Jenkins M, Dubey J P. Immunization of mice with plasmid DNA coding for NcGRA7 or NcsHSP33 confers partial protection against vertical transmission of Neospora caninum. Journal of Parasitology, 2003, 89(3): 496–500
CrossRef Pubmed Google scholar
[25]
Álvarez-García G, Pitarch A, Zaballos A, Fernández-García A, Gil C, Gómez-Bautista M, Aguado-Martínez A, Ortega-Mora L M. The NcGRA7 gene encodes the immunodominant 17 kDa antigen of Neospora caninum. Parasitology, 2007, 134(1): 41–50
CrossRef Pubmed Google scholar
[26]
Monney T, Rütti D, Schorer M, Debache K, Grandgirard D, Leib S L, Hemphill A. 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, 2011, 29(40): 6967–6975
CrossRef Pubmed Google scholar
[27]
Uchida M, Nagashima K, Akatsuka Y, Murakami T, Ito A, Imai S, Ike K. Comparative study of protective activities of Neospora caninum bradyzoite antigens, NcBAG1, NcBSR4, NcMAG1, and NcSAG4, in a mouse model of acute parasitic infection. Parasitology Research, 2013, 112(2): 655–663
CrossRef Pubmed Google scholar
[28]
Haldorson G J, Mathison B A, Wenberg K, Conrad P A, Dubey J P, Trees A J, Yamane I, Baszler T V. Immunization with native surface protein NcSRS2 induces a Th2 immune response and reduces congenital Neospora caninum transmission in mice. International Journal for Parasitology, 2005, 35(13): 1407–1415
CrossRef Pubmed Google scholar
[29]
Ramamoorthy S, Sanakkayala N, Vemulapalli R, Duncan R B, Lindsay D S, Schurig G S, Boyle S M, Kasimanickam R, Sriranganathan N. Prevention of lethal experimental infection of C57BL/6 mice by vaccination with Brucella abortus strain RB51 expressing Neospora caninum antigens. International Journal for Parasitology, 2007, 37(13): 1521–1529
CrossRef Pubmed Google scholar
[30]
Rojo-Montejo S, Collantes-Fernández E, Regidor-Cerrillo J, Rodríguez-Bertos A, Prenafeta A, Gomez-Bautista M, Ortega-Mora L M. Influence of adjuvant and antigen dose on protection induced by an inactivated whole vaccine against Neospora caninum infection in mice. Veterinary Research, 2011, 175(3–4): 220–229
Pubmed
[31]
Hemphill A, Debache K, Monney T, Schorer M, Guionaud C, Alaeddine F, Mueller N, Mueller J. Proteins mediating the Neospora caninum-host cell interaction as targets for vaccination. Frontiers in Bioscience, 2013, 5(1): 23–36
CrossRef Pubmed Google scholar
[32]
Ahmadpour E, Sarvi S, Hashemi Soteh M B, Sharif M, Rahimi M T, Valadan R, Tehrani M, Khalilian A, Montazeri M, Daryani A. Evaluation of the immune response in BALB/c mice induced by a novel DNA vaccine expressing GRA14 against Toxoplasma gondii. Parasite Immunology, 2017, 39(4): e12419
CrossRef Pubmed Google scholar

Acknowledgements

Project support was provided by the National Key Research and Development Program of China (2017YFD0501200), the National Key Basic Research Program (973 program) of China (2015CB150300), the National Natural Science Foundation of China (31772730).
Compliance with ethics guidelines Taotao Zhang, Xiao Zhang, Qun Liu, Jianhai Xu, and Jing Liu declare that they have no conflicts of interest or financial conflicts to disclose. All applicable institutional and national guidelines for the care and use of animals were followed.

RIGHTS & PERMISSIONS

The Author(s) 2019. Published by Higher Education Press. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0)
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