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Bhattarai, Acta Trop. 94:163-169, 2005); ultimately successful vaccine strategies will undoubtedly be multifactorial, incorporating multiple antigens and targeting diverse aspects of the malaria parasites\u2019 biology (M. F. Good et al., Immunol. Rev. 201:254-267, 2004). Using a murine model of malaria infection, we show here that exposure to bites from uninfected mosquitoes prior to<jats:italic>Plasmodium yoelii<\/jats:italic>infection influences the local and systemic immune responses and limits parasite development within the host. In hosts preexposed to bites from uninfected mosquitoes, reduced parasite burdens in the livers were detected early, and during the blood-stage of the life cycle, these burdens remained lower than those in hosts that received mosquito bites only at the time of infection. Repeated exposure to bites from uninfected mosquitoes skewed the immune response towards a T-helper 1 (Th1) phenotype as indicated by increased levels of interleukin-12, gamma interferon, and inducible nitric oxide synthase. These data suggest that the addition of mosquito salivary components to antimalaria vaccines may be a viable strategy for creating a Th1-biased environment known to be effective against malaria infection. Furthermore, this strategy may be important for the development of vaccines to combat other mosquito-transmitted pathogens.<\/jats:p>","DOI":"10.1128\/iai.01928-06","type":"journal-article","created":{"date-parts":[[2007,3,6]],"date-time":"2007-03-06T01:28:43Z","timestamp":1173144523000},"page":"2523-2530","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":107,"title":["Uninfected Mosquito Bites Confer Protection against Infection with Malaria Parasites"],"prefix":"10.1128","volume":"75","author":[{"given":"Michael J.","family":"Donovan","sequence":"first","affiliation":[{"name":"Center for Global Health and Infectious Diseases, Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana 46556"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew S.","family":"Messmore","sequence":"additional","affiliation":[{"name":"Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah A.","family":"Scrafford","sequence":"additional","affiliation":[{"name":"Center for Global Health and Infectious Diseases, Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana 46556"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L.","family":"Sacks","sequence":"additional","affiliation":[{"name":"Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaden","family":"Kamhawi","sequence":"additional","affiliation":[{"name":"Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Ann","family":"McDowell","sequence":"additional","affiliation":[{"name":"Center for Global Health and Infectious Diseases, Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana 46556"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4894(76)90091-6"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/238341a0"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01200448"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.188.10.1941"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.4.2487"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3024.2006.00805.x"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.actatropica.2005.04.015"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182004004834"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0020-7519(01)00265-X"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1159\/000023955"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004360050699"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1984.33.538"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.7.4141"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.65.5.1593-1598.1997"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1086\/339408"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.3.1453"},{"key":"e_1_3_2_18_2","doi-asserted-by":"crossref","first-page":"884","DOI":"10.4049\/jimmunol.163.2.884","volume":"163","year":"1999","unstructured":"Doolan, D. 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