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However, we have no antiviral therapies against alphaviral disease, and current vaccine strategies target only a single alphavirus species. In an effort to develop new tools for a broader response to outbreaks, we designed and tested a novel alphavirus vaccine comprised of cationic lipid nucleic acid complexes (CLNCs) and the ectodomain of WEEV E1 protein (E1ecto). Interestingly, we found that the CLNC component, alone, had therapeutic efficacy, as it increased survival of CD-1 mice following lethal WEEV infection. Immunization with the CLNC-WEEV E1ecto mixture (lipid-antigen-nucleic acid complexes [LANACs]) using a prime-boost regimen provided 100% protection in mice challenged with WEEV subcutaneously, intranasally, or via mosquito. Mice immunized with LANACs mounted a strong humoral immune response but did not produce neutralizing antibodies. Passive transfer of serum from LANAC E1ecto-immunized mice to nonimmune CD-1 mice conferred protection against WEEV challenge, indicating that antibody is sufficient for protection. In addition, the LANAC E1ecto immunization protocol significantly increased survival of mice following intranasal or subcutaneous challenge with EEEV. In summary, our LANAC formulation has therapeutic potential and is an effective vaccine strategy that offers protection against two distinct species of alphavirus irrespective of the route of infection. We discuss plausible mechanisms as well the potential utility of our LANAC formulation as a pan-alphavirus vaccine.<\/jats:p>","DOI":"10.1128\/jvi.02297-13","type":"journal-article","created":{"date-parts":[[2013,11,21]],"date-time":"2013-11-21T03:15:58Z","timestamp":1385003758000},"page":"1771-1780","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":19,"title":["Liposome-Antigen-Nucleic Acid Complexes Protect Mice from Lethal Challenge with Western and Eastern Equine Encephalitis Viruses"],"prefix":"10.1128","volume":"88","author":[{"given":"Aaron T.","family":"Phillips","sequence":"first","affiliation":[{"name":"Arthropod-Borne and Infectious Disease Laboratory, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony","family":"Schountz","sequence":"additional","affiliation":[{"name":"Arthropod-Borne and Infectious Disease Laboratory, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann M.","family":"Toth","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, University of Wyoming, Laramie, Wyoming, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amber B.","family":"Rico","sequence":"additional","affiliation":[{"name":"Arthropod-Borne and Infectious Disease Laboratory, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald L.","family":"Jarvis","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, University of Wyoming, Laramie, Wyoming, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann M.","family":"Powers","sequence":"additional","affiliation":[{"name":"Division of Vector-Borne Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken E.","family":"Olson","sequence":"additional","affiliation":[{"name":"Arthropod-Borne and Infectious Disease Laboratory, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00670.x"},{"key":"e_1_3_2_3_2","volume-title":"Immunization of persons at risk of exposure to eastern equine encephalitis virus: continued assessment of the safety and effectiveness of eastern equine encephalitis vaccine, inactivated, TSI-GSD 104 (protocol no. 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