{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T04:12:50Z","timestamp":1794370370038,"version":"4.9.0"},"reference-count":71,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2019,10,27]],"date-time":"2019-10-27T00:00:00Z","timestamp":1572134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21AI137790"],"award-info":[{"award-number":["R21AI137790"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"New York Blood Center","award":["NYB616"],"award-info":[{"award-number":["NYB616"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Zika virus (ZIKV), a mosquito-borne flavivirus, has attracted global attention due to its close association with congenital Zika syndrome and neurological diseases, and transmission through additional routes, such as sexual contact. Currently there are no vaccines approved for ZIKV, and thus, there is an urgent need to develop an effective and safe ZIKV vaccine. Domain III (DIII) of the ZIKV envelope (E) protein is an important vaccine target, and a vaccine developed using a mutant DIII of E (EDIII) protein protects adult and pregnant mice, and unborn offspring, against ZIKV infection. Here, we have used immunocompetent BALB\/c mice treated with anti-interferon-\u03b1\/\u03b2 receptor 1 (Ifnar1) antibodies to investigate whether three adjuvants (aluminum (Alum), monophosphoryl lipid A (MPL), and MF59), either alone or in combination, could improve the efficacy of this EDIII subunit vaccine. Our data show that, although vaccine formulated with a single adjuvant induced a specific antibody and cellular immune response, and reduced viral load in mice challenged with ZIKV, the combination of Alum and MPL adjuvants led to a more robust and balanced immune response, stronger neutralizing activity against three recent ZIKV human strains, and greater protection against a high-dose ZIKV challenge. Particularly, the combination of Alum with MPL significantly reduced viral titers and viral RNA copy numbers in sera and tissues, including the male reproductive organs. Overall, this study has identified the combination of Alum and MPL as the most effective adjuvant for ZIKV EDIII subunit vaccines, and it has important implications for subunit vaccines against other enveloped viruses, including non-ZIKV flaviviruses.<\/jats:p>","DOI":"10.3390\/vaccines7040161","type":"journal-article","created":{"date-parts":[[2019,10,28]],"date-time":"2019-10-28T04:44:31Z","timestamp":1572237871000},"page":"161","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Effects of Adjuvants on the Immunogenicity and Efficacy of a Zika Virus Envelope Domain III Subunit Vaccine"],"prefix":"10.3390","volume":"7","author":[{"given":"Xinyi","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Medical School, Southeast University, Nanjing 210009, China"},{"name":"Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9864-8993","authenticated-orcid":false,"given":"Wanbo","family":"Tai","sequence":"additional","affiliation":[{"name":"Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolu","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusen","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China"},{"name":"Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanying","family":"Du","sequence":"additional","affiliation":[{"name":"Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3748-3742","authenticated-orcid":false,"given":"Chuanlai","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Medical School, Southeast University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/0035-9203(52)90042-4","article-title":"Zika virus. I. Isolations and serological specificity","volume":"46","author":"Dick","year":"1952","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Krauer, F., and Riesen, M. (2017). 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