Characterization of a Novel Chimeric Theileria parva p67 Antigen Which Incorporates into Virus-like Particles and Is Highly Immunogenic in Mice
Abstract
:1. Introduction
2. Materials and Methods
2.1. Plasmids, Cells and Primary Antibodies
2.2. Confirmation of p67, p67HA and BLV Gag Expression
2.3. VLP Isolation, Immunogold-Labelling and Electron Microscopy
2.4. Characterization of p67ΔTM Protein
2.5. Purification of p67ΔTM and BLV Gag Protein
2.6. Mouse Immunizations
2.7. ELISAs for p67- and BLV Gag-Binding Antibodies
3. Results
3.1. Confirmation of p67, p67HA and BLV Gag Expression
3.2. Presence of p67HA on the Cell Surface and Isolated VLPs
3.3. Characterisation of p67ΔTM Expression
3.4. Immunogenicity of p67, p67HA and p67HA-VLPs
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
References
- Byaruhanga, C.; Oosthuizen, M.; Collins, N.; Knobel, D. Using participatory epidemiology to investigate management options and relative importance of tick-borne diseases amongst transhumant zebu cattle in Karamoja Region, Uganda. Prev. Veter. Med. 2015, 122, 287–297. [Google Scholar] [CrossRef] [Green Version]
- Nene, V.; Kiara, H.; Lacasta, A.; Pelle, R.; Svitek, N.; Steinaa, L. The biology of Theileria parva and control of East Coast fever—Current status and future trends. Ticks Tick Borne Dis. 2016, 7, 549–564. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Silatsa, B.A.; Simo, G.; Githaka, N.; Kamga, R.; Oumarou, F.; Tiambo, C.K.; Machuka, E.; Domelevo, J.; Odongo, D.; Bishop, R.; et al. First detection of Theileria parva in cattle from Cameroon in the absence of the main tick vector Rhipicephalus appendiculatus. Transbound. Emerg. Dis. 2020, 67 (Suppl. 1), 68–78. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kivaria, F.M. Estimated direct economic costs associated with tick-borne diseases on cattle in Tanzania. Trop. Anim. Health Prod. 2006, 38, 291–299. [Google Scholar] [CrossRef]
- Kimaro, E.G.; Toribio, J.-A.L.; Mor, S.M. Climate change and cattle vector-borne diseases: Use of participatory epidemiology to investigate experiences in pastoral communities in Northern Tanzania. Prev. Veter. Med. 2017, 147, 79–89. [Google Scholar] [CrossRef]
- Boucher, F.; Moutroifi, Y.; Ali, M.; Moindjie, Y.; Soulé, M.; Charafouddine, O.; Cêtre-Sossah, C.; Cardinale, E. Impact of East Coast fever on Grande Comore: Assessment taking a participatory epidemiology approach. Trop. Anim. Health Prod. 2019, 51, 99–107. [Google Scholar] [CrossRef]
- Nthiwa, D.; Alonso, S.; Odongo, D.; Kenya, E.; Bett, B. A participatory epidemiological study of major cattle diseases amongst Maasai pastoralists living in wildlife-livestock interfaces in Maasai Mara, Kenya. Trop. Anim. Health Prod. 2019, 51, 1097–1103. [Google Scholar] [CrossRef] [Green Version]
- Malak, A.; Mpoke, L.; Banak, J.; Muriuki, S.; Skilton, R.; Odongo, D.; Sunter, J.; Kiara, H. Prevalence of livestock diseases and their impact on livelihoods in Central Equatoria State, southern Sudan. Prev. Veter. Med. 2012, 104, 216–223. [Google Scholar] [CrossRef] [PubMed]
- Bishop, R.; Musoke, A.; Morzaria, S.; Gardner, M.; Nene, V. Theileria: Intracellular protozoan parasites of wild and domestic ruminants transmitted by ixodid ticks. Parasitology 2004, 129 (Suppl. 1), S271–S283. [Google Scholar] [CrossRef] [PubMed]
- Patel, E.; Mwaura, S.; Kiara, H.; Morzaria, S.; Peters, A.; Toye, P. Production and dose determination of the Infection and Treatment Method (ITM) Muguga cocktail vaccine used to control East Coast fever in cattle. Ticks Tick Borne Dis. 2016, 7, 306–314. [Google Scholar] [CrossRef]
- Di Giulio, G.; Lynen, G.; Morzaria, S.; Oura, C.; Bishop, R. Live immunization against East Coast fever—Current status. Trends Parasitol. 2009, 25, 85–92. [Google Scholar] [CrossRef] [PubMed]
- Bishop, R.P.; Odongo, D.O.; Spooner, P.R.; Morzaria, S.P.; Oura, C.A.L.; Skilton, R.A. Multilocus genotyping of Theileria parva isolates associated with a live vaccination trial in Kenya provides evidence for transmission of immunizing parasites into local tick and cattle populations. Transbound. Emerg. Dis. 2020, 67, 88–98. [Google Scholar] [CrossRef] [PubMed]
- De Deken, R.; Martin, V.; Saido, A.; Madder, M.; Brandt, J.; Geysen, D. An outbreak of East Coast Fever on the Comoros: A consequence of the import of immunised cattle from Tanzania? Vet. Parasitol. 2007, 143, 245–253. [Google Scholar] [CrossRef] [PubMed]
- Nene, V.; Morrison, W.I. Approaches to vaccination against Theileria parva and Theileria annulata. Parasite Immunol. 2016, 38, 724–734. [Google Scholar] [CrossRef] [Green Version]
- Nene, V.; Gobright, E.; Bishop, R.; Morzaria, S.; Musoke, A. Linear Peptide Specificity of Bovine Antibody Responses to p67 of Theileria parva and Sequence Diversity of Sporozoite-Neutralizing Epitopes: Implications for a Vaccine. Infect. Immun. 1999, 67, 1261–1266. [Google Scholar] [CrossRef] [Green Version]
- Shaw, M.K. Cell invasion by Theileria sporozoites. Trends Parasitol. 2003, 19, 2–6. [Google Scholar] [CrossRef]
- Tonui, T.; Corredor-Moreno, P.; Kanduma, E.; Njuguna, J.; Njahira, M.N.; Nyanjom, S.G.; Silva, J.C.; Djikeng, A.; Pelle, R. Transcriptomics reveal potential vaccine antigens and a drastic increase of upregulated genes during Theileria parva development from arthropod to bovine infective stages. PLoS ONE 2018, 13, e0204047. [Google Scholar] [CrossRef] [Green Version]
- Nene, V.; Iams, K.P.; Gobright, E.; Musoke, A.J. Characterisation of the gene encoding a candidate vaccine antigen of Theileria parva sporozoites. Mol. Biochem. Parasitol. 1992, 51, 17–28. [Google Scholar] [CrossRef]
- Kaba, S.A.; Nene, V.; Musoke, A.J.; Vlak, J.M.; VAN Oers, M.M. Fusion to green fluorescent protein improves expression levels of Theileria parva sporozoite surface antigen p67 in insect cells. Parasitology 2002, 125 Pt 6, 497–505. [Google Scholar] [CrossRef] [Green Version]
- Bishop, R.; Nene, V.; Staeyert, J.; Rowlands, J.; Nyanjui, J.; Osaso, J.; Morzaria, S.; Musoke, A. Immunity to East Coast fever in cattle induced by a polypeptide fragment of the major surface coat protein of Theileria parva sporozoites. Vaccine 2003, 21, 1205–1212. [Google Scholar] [CrossRef]
- Nene, V.; Inumaru, S.; McKeever, D.; Morzaria, S.; Shaw, M.; Musoke, A. Characterization of an insect cell-derived Theileria parva sporozoite vaccine antigen and immunogenicity in cattle. Infect. Immun. 1995, 63, 503–508. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tebaldi, G.; Williams, L.B.; Verna, A.E.; Macchi, F.; Franceschi, V.; Fry, L.M.; Knowles, D.P.; Donofrio, G. Assessment and optimization of Theileria parva sporozoite full-length p67 antigen expression in mammalian cells. PLoS Negl. Trop. Dis. 2017, 11, e0005803. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Musoke, A.; Rowlands, J.; Nene, V.; Nyanjui, J.; Katende, J.; Spooner, P.; Mwaura, S.; Odongo, D.; Nkonge, C.; Mbogo, S.; et al. Subunit vaccine based on the p67 major surface protein of Theileria parva sporozoites reduces severity of infection derived from field tick challenge. Vaccine 2005, 23, 3084–3095. [Google Scholar] [CrossRef]
- Kaba, S.A.; Hemmes, J.C.; Van Lent, J.W.; Vlak, J.M.; Nene, V.; Musoke, A.J.; Van Oers, M.M. Baculovirus surface display of Theileria parva p67 antigen preserves the conformation of sporozoite-neutralizing epitopes. Protein Eng. Des. Sel. 2003, 16, 73–78. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lacasta, A.; Mwalimu, S.; Kibwana, E.; Saya, R.; Awino, E.; Njoroge, T.; Poole, J.; Ndiwa, N.; Pelle, R.; Nene, V.; et al. Immune parameters to p67C antigen adjuvanted with ISA206VG correlate with protection against East Coast fever. Vaccine 2018, 36, 1389–1397. [Google Scholar] [CrossRef] [PubMed]
- Kaba, S.A.; Schaap, D.; Roode, E.C.; Nene, V.; Musoke, A.J.; Vlak, J.M.; Van Oers, M.M. Improved immunogenicity of novel baculovirus-derived Theileria parva p67 subunit antigens. Veter. Parasitol. 2004, 121, 53–64. [Google Scholar] [CrossRef] [PubMed]
- Lacasta, A.; Mody, K.T.; De Goeyse, I.; Yu, C.; Zhang, J.; Nyagwange, J.; Mwalimu, S.; Awino, E.; Saya, R.; Njoroge, T.; et al. Synergistic Effect of Two Nanotechnologies Enhances the Protective Capacity of the Theileria parva Sporozoite p67C Antigen in Cattle. J. Immunol. 2021, 206, 686–699. [Google Scholar] [CrossRef] [PubMed]
- Lee, K.L.; Twyman, R.M.; Fiering, S.; Steinmetz, N.F. Virus-based nanoparticles as platform technologies for modern vaccines. WIREs Nanomed. Nanobiotechnol. 2016, 8, 554–578. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Smith, M.L.; Lindbo, J.A.; Dillard-Telm, S.; Brosio, P.M.; Lasnik, A.B.; McCormick, A.A.; Nguyen, L.V.; Palmer, K.E. Modified Tobacco mosaic virus particles as scaffolds for display of protein antigens for vaccine applications. Virology 2006, 348, 475–488. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- McBurney, S.P.; Young, K.R.; Ross, T.M. Membrane embedded HIV-1 envelope on the surface of a virus-like particle elicits broader immune responses than soluble envelopes. Virology 2007, 358, 334–346. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kaba, S.A.; Musoke, A.J.; Schaap, D.; Schetters, T.; Rowlands, J.; Vermeulen, A.N.; Nene, V.; Vlak, J.M.; Van Oers, M.M. Novel baculovirus-derived p67 subunit vaccines efficacious against East Coast fever in cattle. Vaccine 2005, 23, 2791–2800. [Google Scholar] [CrossRef] [PubMed]
- Rheinemann, L.; Sundquist, W.I. Virus Budding. Encycl. Virol. 2021, 519–528. [Google Scholar] [CrossRef]
- Musoke, A.J.; Nantulya, V.M.; Rurangirwa, F.R.; Buscher, G. Evidence for a common protective antigenic determinant on sporozoites of several Theileria parva strains. Immunology 1984, 52, 231–238. [Google Scholar] [PubMed]
- Wang, B.-Z.; Liu, W.; Kang, S.-M.; Alam, M.; Huang, C.; Ye, L.; Sun, Y.; Li, Y.; Kothe, D.L.; Pushko, P.; et al. Incorporation of High Levels of Chimeric Human Immunodeficiency Virus Envelope Glycoproteins into Virus-Like Particles. J. Virol. 2007, 81, 10869–10878. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chapman, R.; van Diepen, M.; Galant, S.; Kruse, E.; Margolin, E.; Ximba, P.; Hermanus, T.; Moore, P.; Douglass, N.; Williamson, A.-L.; et al. Immunogenicity of HIV-1 Vaccines Expressing Chimeric Envelope Glycoproteins on the Surface of Pr55 Gag Virus-Like Particles. Vaccines 2020, 8, 54. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Vzorov, A.N.; Wang, L.; Chen, J.; Wang, B.-Z.; Compans, R.W. Effects of modification of the HIV-1 Env cytoplasmic tail on immunogenicity of VLP vaccines. Virology 2016, 489, 141–150. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Barez, P.-Y.; De Brogniez, A.; Carpentier, A.; Gazon, H.; Gillet, N.; Gutiérrez, G.; Hamaidia, M.; Jacques, J.-R.; Perike, S.; Neelature Sriramareddy, S.; et al. Recent Advances in BLV Research. Viruses 2015, 7, 6080–6088. [Google Scholar] [CrossRef]
- Käll, L.; Krogh, A.; Sonnhammer, E. Advantages of combined transmembrane topology and signal peptide prediction--the Phobius web server. Nucleic Acids Res. 2007, 35, W429–W432. [Google Scholar] [CrossRef] [Green Version]
- Tanzer, F.L.; Shephard, E.G.; E Palmer, K.; Burger, M.; Williamson, A.-L.; Rybicki, E.P. The porcine circovirus type 1 capsid gene promoter improves antigen expression and immunogenicity in a HIV-1 plasmid vaccine. Virol. J. 2011, 8, 51. [Google Scholar] [CrossRef] [Green Version]
- Van Diepen, M.T.; Chapman, R.; Douglass, N.; Galant, S.; Moore, P.L.; Margolin, E.; Ximba, P.; Morris, L.; Rybicki, E.P.; Williamson, A.L. Prime-boost Iunizations with DNA, Modified Vaccinia Virus Ankara, and Protein-Based Vaccines Elicit Robust HIV-1 Tier 2 Neutralizing Antibodies against the CAP256 Superinfecting Virus. J. Virol. 2019, 93, e02155-18. [Google Scholar] [CrossRef] [Green Version]
- Chapman, R.; Jongwe, T.I.; Douglass, N.; Chege, G.; Williamson, A.-L. Heterologous prime-boost vaccination with DNA and MVA vaccines, expressing HIV-1 subtype C mosaic Gag virus-like particles, is highly immunogenic in mice. PLoS ONE 2017, 12, e0173352. [Google Scholar] [CrossRef] [PubMed]
- Provost and Wallert. His Tag Purification: Purification Protocol. Investigating the Biochemistry & Cellular Physiology of NHE1 2015. Available online: http://home.sandiego.edu/~josephprovost/2015%20His%20tag%20Purification%20Protocol.pdf (accessed on 6 May 2020).
- Musoke, A.; Morzaria, S.; Nkonge, C.; Jones, E.; Nene, V. A recombinant sporozoite surface antigen of Theileria parva induces protection in cattle. Proc. Natl. Acad. Sci. USA 1992, 89, 514–518. [Google Scholar] [CrossRef] [Green Version]
- Kaba, S.A.; Salcedo, A.M.; Wafula, P.O.; Vlak, J.M.; van Oers, M.M. Development of a chitinase and v-cathepsin negative bacmid for improved integrity of secreted recombinant proteins. J. Virol. Methods 2004, 122, 113–118. [Google Scholar] [CrossRef] [PubMed]
- Dobbelaere, D.A.; Webster, P.; Leitch, B.L.; Voigt, W.P.; Irvin, A.D. Theileria parva: Expression of a sporozoite surface coat antigen. Exp. Parasitol. 1985, 60, 90–100. [Google Scholar] [CrossRef]
- Andersson, A.-M.C.; Resende, M.; Salanti, A.; Nielsen, M.A.; Holst, P.J. Novel adenovirus encoded virus-like particles displaying the placental malaria associated VAR2CSA antigen. Vaccine 2017, 35, 1140–1147. [Google Scholar] [CrossRef] [PubMed]
- Haynes, J.R.; Dokken, L.; Wiley, J.A.; Cawthon, A.G.; Bigger, J.; Harmsen, A.G.; Richardson, C. Influenza-pseudotyped Gag virus-like particle vaccines provide broad protection against highly pathogenic avian influenza challenge. Vaccine 2009, 27, 530–541. [Google Scholar] [CrossRef]
- Suzuki, A.; Chapman, R.; Douglass, N.; Carulei, O.; Van Rensburg, J.; Williamson, A.-L. Phylogenetic Analysis of South African Bovine Leukaemia Virus (BLV) Isolates. Viruses 2020, 12, 898. [Google Scholar] [CrossRef]
- Williamson, A.-L.; Rybicki, E.P. Justification for the inclusion of Gag in HIV vaccine candidates. Expert Rev. Vaccines 2015, 15, 585–598. [Google Scholar] [CrossRef]
- Chapman, R.; Rybicki, E.P. Use of a Novel Enhanced DNA Vaccine Vector for Preclinical Virus Vaccine Investigation. Vaccines 2019, 7, 50. [Google Scholar] [CrossRef] [Green Version]
- Babiuk, L.A.; Pontarollo, R.; Babiuk, S.; Loehr, B. Induction ofimmune responses by DNA vaccines in large animals. Vaccine 2003, 21, 649–658. [Google Scholar] [CrossRef]
- Fry, L.M.; Bastos, R.G.; Stone, B.C.; Williams, L.B.; Knowles, D.P.; Murphy, S.C. Gene gun DNA immunization of cattle induces humoral and CD4 T-cell-mediated immune responses against the Theileria parva polymorphic immunodominant molecule. Vaccine 2019, 37, 1546–1553. [Google Scholar] [CrossRef] [PubMed]
- Toussaint, J.-F.; Letellier, C.; Paquet, D.; Dispas, M.; Kerkhofs, P. Prime-boost strategies combining DNA and inactivated vaccines confer high immunity and protection in cattle against bovine herpesvirus-1. Vaccine 2005, 23, 5073–5081. [Google Scholar] [CrossRef] [PubMed]
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Whittle, L.; Chapman, R.; van Diepen, M.; Rybicki, E.P.; Williamson, A.-L. Characterization of a Novel Chimeric Theileria parva p67 Antigen Which Incorporates into Virus-like Particles and Is Highly Immunogenic in Mice. Vaccines 2022, 10, 210. https://doi.org/10.3390/vaccines10020210
Whittle L, Chapman R, van Diepen M, Rybicki EP, Williamson A-L. Characterization of a Novel Chimeric Theileria parva p67 Antigen Which Incorporates into Virus-like Particles and Is Highly Immunogenic in Mice. Vaccines. 2022; 10(2):210. https://doi.org/10.3390/vaccines10020210
Chicago/Turabian StyleWhittle, Leah, Ros Chapman, Michiel van Diepen, Edward P. Rybicki, and Anna-Lise Williamson. 2022. "Characterization of a Novel Chimeric Theileria parva p67 Antigen Which Incorporates into Virus-like Particles and Is Highly Immunogenic in Mice" Vaccines 10, no. 2: 210. https://doi.org/10.3390/vaccines10020210