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Vet. Sci."],"abstract":"<jats:p>Both strong innate and adaptive immune responses are an important component of protection against intraerythrocytic protozoan parasites. Resistance to bovine babesiosis is associated with interferon (IFN)-\u03b3 mediated responses. CD4<jats:sup>+<\/jats:sup> T cells and macrophages have been identified as major effector cells mediating the clearance of pathogens. Previously, the apical membrane antigen 1 (AMA-1) was found to significantly induce the immune response inhibiting <jats:italic>B. bovis<\/jats:italic> merozoite growth and invasion. However, a detailed characterization of both humoral and cellular immune responses against the structure of <jats:italic>B. bovis<\/jats:italic> AMA-1 (BbAMA-1) has not yet been established. Herein, the present study aimed to express the recombinant BbAMA-1 domain I+II protein [rBbAMA-1(I\/II)], which is the most predominant immune response region, and to characterize its immune response. As a result, cattle vaccinated with BbAMA-1(I\/II) significantly developed high titters of total immunoglobulin (Ig) G antibodies and a high ratio of IgG2\/IgG1 when compared to control groups. Interestingly, the BbAMA-1(I\/II)-based formulations produced in our study could elicit CD4<jats:sup>+<\/jats:sup> T cells and CD8<jats:sup>+<\/jats:sup> T cells producing IFN-\u03b3 and tumor necrosis factor (TNF)-\u03b1. Collectively, the results indicate that immunization of cattle with BbAMA-1(I\/II) could induce strong Th1 cell responses. In support of this, we observed the up-regulation of Th1 cytokine mRNA transcripts, including <jats:italic>IFN-<\/jats:italic>\u03b3, <jats:italic>TNF-<\/jats:italic>\u03b1, Interleukin <jats:italic>(IL)-2<\/jats:italic> and <jats:italic>IL-12<\/jats:italic>, in contrast to down regulation of <jats:italic>IL-4, IL-6<\/jats:italic> and <jats:italic>IL-10<\/jats:italic>, which would be indicative of a Th2 cytokine response. Moreover, the up-regulation of inducible nitric oxide synthase (<jats:italic>iNOS<\/jats:italic>) was observed. In conclusion, this is the first report on the in-depth immunological characterization of the response to BbAMA-1. According to our results, BbAMA-1 is recognized as a potential candidate vaccine against <jats:italic>B. bovis<\/jats:italic> infection. As evidenced by the Th1 cell response, it could potentially provide protective immunity. However, further challenge-exposure with virulent <jats:italic>B. bovis<\/jats:italic> strain in immunized cattle would be needed to determine its protective efficacy.<\/jats:p>","DOI":"10.3389\/fvets.2022.917389","type":"journal-article","created":{"date-parts":[[2022,6,23]],"date-time":"2022-06-23T09:38:40Z","timestamp":1655977120000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Immunization of Cattle With Recombinant Structural Ectodomains I and II of Babesia bovis Apical Membrane Antigen 1 [BbAMA-1(I\/II)] Induces Strong Th1 Immune Response"],"prefix":"10.3389","volume":"9","author":[{"given":"Amarin","family":"Rittipornlertrak","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boondarika","family":"Nambooppha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anucha","family":"Muenthaisong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nisachon","family":"Apinda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pongpisid","family":"Koonyosying","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanwisa","family":"Srisawat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paweena","family":"Chomjit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanokwan","family":"Sangkakam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veerasak","family":"Punyapornwithaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saruda","family":"Tiwananthagorn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoaki","family":"Yokoyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nattawooti","family":"Sthitmatee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"S247","DOI":"10.1017\/S0031182004005190","article-title":"Babesiosis of cattle","volume":"129","author":"Bock","year":"2004","journal-title":"Parasitology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.ijpara.2018.11.002","article-title":"Unraveling the cellular and molecular pathogenesis of bovine babesiosis: is the sky the limit?","volume":"49","author":"Suarez","year":"2019","journal-title":"Int J Parasitol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.ijpddr.2019.02.001","article-title":"Development of unstable resistance to diminazene aceturate in Babesia bovis","volume":"9","author":"Tuvshintulga","year":"2019","journal-title":"Int J Parasitol Drugs Drug Resist"},{"key":"B4","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1111\/j.1365-3024.2006.00849.x","article-title":"Prospects for recombinant vaccines against Babesia bovis and related parasites","volume":"28","author":"Brown","year":"2006","journal-title":"Parasite Immunol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1083\/jcb.77.1.72","article-title":"Erythrocyte entry by malarial parasites. 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