{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T13:06:52Z","timestamp":1759410412207},"reference-count":29,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2008,9,18]],"date-time":"2008-09-18T00:00:00Z","timestamp":1221696000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Scand J Immunol"],"published-print":{"date-parts":[[2008,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>T\u2010cell mediated immune responses are key determinants to the natural course of infection caused by intracellular parasites such as <jats:italic>Leishmania<\/jats:italic>. Thus, T\u2010cell activating proteins of these microbes continue to generate active interest particularly in view of their possible role in the design and development of newer and more effective vaccines. We have recently reported the presence of T\u2010cell immunostimulatory antigens with the high\u2010molecular\u2010weight (MW) fractions (134\u201364.2\u2003kDa) of whole <jats:italic>Leishmania donovani<\/jats:italic> antigen (strain 2001), which stimulated variable amounts of IFN\u2010\u03b3, IL\u201012 and IL\u201010 in exposed immune individuals. The present study was undertaken to further evaluate these high\u2010MW antigenic fractions (MW range &gt;100\u201360\u2003kDa) for potential protective efficacy. The high\u2010MW region of the parasite was resolved into five antigenic fractions (Prep A\u2013E) using continuous elution gel electrophoresis. Prior to <jats:italic>in vivo<\/jats:italic> protection studies in hamsters, these fractions were used to evaluate <jats:italic>in vitro<\/jats:italic> cellular responses in eight <jats:italic>Leishmania<\/jats:italic>\u2010exposed individuals and treated cured hamsters. The protective efficacy of prep (A\u2003+\u2003B), C, D and E in combination with BCG was evaluated in inbred hamsters using standard immunization protocol. Proliferative responses were seen in all eight of eight exposed individuals to prep D [median stimulation index (SI): 5.2 (range 3.9\u20137.1)] and E [median SI: 5.6 (range 4.4\u20138.2)], five of eight individuals to prep B and prep C and three of eight to prep A [median SI: 0.2 (range 0.1\u20137.2)]. The median proliferative responses to prep D and prep E were significantly higher than to fraction prep A; (<jats:italic>P<\/jats:italic>\u2003&lt;\u20030.05) but not to prep B and prep C. However, prep A\u2013E induced equivalent levels of IFN\u2010\u03b3, IL\u201010 and IL\u201012 cytokines. Fractions D and E also exhibited marked parasite inhibition in spleen (52.5% and 73.7%) and liver (65% and 80.2%) as compared with prep (A\u2003+\u2003B) (23% in spleen and 24% in liver) and prep C (38% in spleen and 24% in liver). Prep D and prep E vaccinated animals showed higher <jats:italic>in vitro<\/jats:italic> stimulatory responses (mean SI: 6.6 and 8.8) and nitric oxide (NO) induction (mean NO levels: 6.4 and 10.7\u2003<jats:italic>\u03bc<\/jats:italic>g\/ml) against whole cell extract as compared with other groups. The protection also correlated with presence of suppressed <jats:italic>Leishmania<\/jats:italic>\u2010specific IgG levels in prep D and prep E immunized hamsters. These studies indicate the presence of immunostimulatory and protective molecules in 60\u201380\u2003kDa region of <jats:italic>L. donovani<\/jats:italic>, which may be further exploited for developing a subunit vaccine.<\/jats:p>","DOI":"10.1111\/j.1365-3083.2008.02171.x","type":"journal-article","created":{"date-parts":[[2008,9,18]],"date-time":"2008-09-18T06:32:12Z","timestamp":1221719532000},"page":"492-501","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Prophylactic Efficacy of High\u2010Molecular\u2010Weight Antigenic Fractions of a Recent Clinical Isolate of <i>Leishmania donovani<\/i> Against Visceral Leishmaniasis"],"prefix":"10.1111","volume":"68","author":[{"given":"P.","family":"Tripathi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. 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