{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T13:47:17Z","timestamp":1785937637460,"version":"3.56.0"},"reference-count":60,"publisher":"American Society of Tropical Medicine and Hygiene","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,5]]},"abstract":"<jats:title>ABSTRACT.<\/jats:title>\n                  <jats:p>West Nile Virus (WNV) is endemic throughout the world and is a leading cause of mosquito-borne severe and\/or fatal encephalitic disease. Although several promising WNV vaccines have been developed, none have been approved for human use. Studies were conducted to evaluate the immunogenicity, protective efficacy, and safety of a recombinant subunit WNV candidate vaccine (WN-80E) formulated with aluminum hydroxide (Alhydrogel\u2122) adjuvant and\/or in combination with a semi-synthetic saponin (GPI-0100) adjuvant in mice and hamsters, and for toxicology, immunogenicity and safety in rabbits. Adult mice and hamsters were immunized twice via the intramuscular (IM) route 3 to 4 weeks apart with escalating doses of WN-80E adsorbed to Alhydrogel\u2122. Mice were also immunized with WN-80E in combination with the GPI-0100 adjuvant. All animals were subsequently challenged with a lethal dose of virulent WNV. The rabbits received four IM immunizations 3 weeks apart with WN-80E\/Alhydrogel\u2122 that was compared to WN-80E\/Alhydrogel\u2122 plus various amounts of GPI-0100. The results of immunogenicity and challenge experiments demonstrated that all WN-80E vaccine formulations with Alhydrogel\u2122 with or without GPI-0100 were immunogenic and afforded complete protection to mice and hamsters against morbidity and mortality following challenge with WNV. Also, the WN-80E\/Alhydrogel formulations with or without GPI-0100 were well tolerated and elicited high neutralizing antibody (nAb) titers in rabbits. Cumulatively, because these findings demonstrated that the WN-80E formulated with Alhydrogel\u2122 alone elicited robust antibody responses and protection against viral challenge, this formulation was selected for further evaluation in clinical trials for the prevention of WNV disease in humans.<\/jats:p>","DOI":"10.4269\/ajtmh.26-0133","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T16:11:29Z","timestamp":1784045489000},"page":"372-382","source":"Crossref","is-referenced-by-count":0,"title":["Pre-Clinical Immunogenicity and Protective Efficacy of a Recombinant Subunit West Nile Virus Vaccine Formulated with Aluminum Hydroxide Adjuvant"],"prefix":"10.4269","volume":"115","author":[{"given":"Douglas M.","family":"Watts","sequence":"first","affiliation":[{"name":"University of Texas Medical Branch, Galveston, Texas, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth-Ann G.","family":"Coller","sequence":"additional","affiliation":[{"name":"Hawaii Biotech Inc., Honolulu, Hawaii, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelia P.","family":"Da Rosa Travassos","sequence":"additional","affiliation":[{"name":"University of Texas Medical Branch, Galveston, Texas, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Newman","sequence":"additional","affiliation":[{"name":"University of Texas Medical Branch, Galveston, Texas, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Grant","sequence":"additional","affiliation":[{"name":"University of Texas Medical Branch, Galveston, Texas, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Martyak","sequence":"additional","affiliation":[{"name":"Hawaii Biotech Inc., Honolulu, Hawaii, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhui","family":"Jia","sequence":"additional","affiliation":[{"name":"Family Nurse Practitioners, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E.","family":"Clements","sequence":"additional","affiliation":[{"name":"Hawaii Biotech Inc., Honolulu, Hawaii, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael M.","family":"Lieberman","sequence":"additional","affiliation":[{"name":"Hawaii Biotech Inc., Honolulu, Hawaii, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2795","reference":[{"key":"b1","series-title":"JAMA","first-page":"308","article-title":"West Nile virus: Review of the literature","volume":"310","author":"Petersen","year":"2013"},{"key":"b2","series-title":"J Gen Virol","first-page":"37","article-title":"Antigenic relationships between flaviviruses as determined by cross-neutralization tests with polyclonal antisera","volume":"70","author":"Calisher","year":"1989"},{"key":"b3","series-title":"QJM","first-page":"219","article-title":"Encephalitis caused by flaviviruses","volume":"105","author":"Turtle","year":"2012"},{"key":"b4","series-title":"Annu Rev Entomol","first-page":"61","article-title":"A global perspective on the epidemiology of West Nile virus","volume":"53","author":"Kramer","year":"2008"},{"key":"b5","series-title":"Viruses","first-page":"823","article-title":"Twenty years of progress toward West Nile virus vaccine development","volume":"11","author":"Kaiser","year":"2019"},{"key":"b6","series-title":"Disease Emerg Infect Dis","first-page":"1167","article-title":"Epidemiology and transmission dynamics of West Nile Virus","volume":"11","author":"Hayes","year":"2005"},{"key":"b7","series-title":"West Nile Historic Data (1999-2024).","year":"2026"},{"key":"b8","series-title":"Viruses","first-page":"606","article-title":"Clinical manifestations and outcomes of West Nile virus infection","volume":"6","author":"Sejvar","year":"2014"},{"key":"b9","series-title":"Pathogens","first-page":"193","article-title":"Current understanding of West Nile virus clinical manifestations, immune responses, neuroinvasion, and immuno-therapeutic implications","volume":"8","author":"Bai","year":"2019"},{"key":"b10","series-title":"Vector Borne Zoonotic Dis","first-page":"61","article-title":"The epidemic of West Nile virus in the United States, 2002","volume":"4","author":"O\u2019Leary","year":"2004"},{"key":"b11","series-title":"N Engl J Med","first-page":"1225","article-title":"West Nile virus encephalitis","volume":"347","author":"Petersen","year":"2002"},{"key":"b12","series-title":"Antiviral Research","first-page":"1","article-title":"Resurgence of West Nile neurologic disease in the United States in 2013: What happened? 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