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Considering the importance of both CD4 and CD8 T cells in the control of intracellular pathogens such as<jats:named-content content-type=\"genus-species\">Leishmania donovani<\/jats:named-content>, we wanted to identify vaccines that could raise both CD4 and CD8 T cell responses and determine how to configure immunization strategies to generate the best combined protective T cell response. We examined responses generated against the<jats:named-content content-type=\"genus-species\">Leishmania<\/jats:named-content>vaccine antigen F3 following its administration in either recombinant form with the Toll-like receptor 4 (TLR4) agonist-containing adjuvant formulation GLA-SE (F3+GLA-SE) or as a gene product delivered in an adenoviral vector (Ad5-F3). Homologous immunization strategies using only F3+GLA-SE or Ad5-F3 preferentially generated either CD4 or CD8 T cells, respectively. In contrast, heterologous strategies generated both antigen-specific CD4 and CD8 T cells. Administration of F3+GLA-SE before Ad5-F3 generated the greatest combined CD4 and CD8 responses. Cytotoxic CD8 T cell responses were highest when Th1 cells were generated prior to their induction by Ad5-F3. Finally, a single immunization with a combination of F3+GLA-SE mixed with Ad5-F3 was found to be sufficient to provide protection against experimental<jats:named-content content-type=\"genus-species\">L. donovani<\/jats:named-content>infection. Taken together, our data delineate immunization regimens that induce antigen-specific CD4 and CD8 T cell memory responses, and identify a single immunization strategy that could be used to rapidly provide protection against intracellular pathogens in regions where access to health care is limited or sporadic.<\/jats:p>","DOI":"10.1128\/cvi.00251-16","type":"journal-article","created":{"date-parts":[[2016,7,27]],"date-time":"2016-07-27T22:59:09Z","timestamp":1469660349000},"page":"785-794","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":14,"title":["Optimizing Immunization Strategies for the Induction of Antigen-Specific CD4 and CD8 T Cell Responses for Protection against Intracellular Parasites"],"prefix":"10.1128","volume":"23","author":[{"given":"Kimberly A.","family":"Hofmeyer","sequence":"first","affiliation":[{"name":"Infectious Disease Research Institute, Seattle, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malcolm S.","family":"Duthie","sequence":"additional","affiliation":[{"name":"Infectious Disease Research Institute, Seattle, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John D.","family":"Laurance","sequence":"additional","affiliation":[{"name":"Infectious Disease Research Institute, Seattle, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle A.","family":"Favila","sequence":"additional","affiliation":[{"name":"Infectious Disease Research Institute, Seattle, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neal","family":"Van Hoeven","sequence":"additional","affiliation":[{"name":"Infectious Disease Research Institute, Seattle, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rhea N.","family":"Coler","sequence":"additional","affiliation":[{"name":"Infectious Disease Research Institute, Seattle, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven G.","family":"Reed","sequence":"additional","affiliation":[{"name":"Infectious Disease Research Institute, Seattle, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"doi-asserted-by":"publisher","key":"e_1_3_2_2_2","DOI":"10.1038\/nri.2015.10"},{"doi-asserted-by":"publisher","key":"e_1_3_2_3_2","DOI":"10.1093\/qjmed\/hct116"},{"doi-asserted-by":"publisher","key":"e_1_3_2_4_2","DOI":"10.1371\/journal.pone.0035671"},{"doi-asserted-by":"publisher","key":"e_1_3_2_5_2","DOI":"10.1111\/j.1365-3024.2009.01102.x"},{"doi-asserted-by":"publisher","key":"e_1_3_2_6_2","DOI":"10.1093\/infdis\/jit401"},{"doi-asserted-by":"publisher","key":"e_1_3_2_7_2","DOI":"10.1371\/journal.pntd.0003198"},{"doi-asserted-by":"publisher","key":"e_1_3_2_8_2","DOI":"10.1172\/JCI112209"},{"doi-asserted-by":"publisher","key":"e_1_3_2_9_2","DOI":"10.1371\/journal.ppat.1003053"},{"doi-asserted-by":"publisher","key":"e_1_3_2_10_2","DOI":"10.1371\/journal.pntd.0002914"},{"key":"e_1_3_2_11_2","doi-asserted-by":"crossref","first-page":"5949","DOI":"10.4049\/jimmunol.152.12.5949","article-title":"Restoration of IFN-gamma production and lymphocyte proliferation in visceral leishmaniasis","volume":"152","author":"Carvalho EM","year":"1994","unstructured":"Carvalho EM, Bacellar O, Brownell C, Regis T, Coffman RL, Reed SG. 1994. 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