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The present study aimed to enhance the immunogenic response of a current injectable killed cholera vaccine (KCV) using chitosan and alginate salt as natural adjuvants against alum. We tested KCV adjuvanted with alum, chitosan, and sodium alginate in mice. Mice were immunized intraperitoneally with KCV adjuvanted with alum, chitosan, or alginate salt and compared with a control unadjuvanted immunized group. Humoral, cellular, and functional immune responses were evaluated in all groups. The addition of adjuvants, particularly natural adjuvants, to KCV significantly improved the immune response as demonstrated by specific antibody increase, strong proliferation effects, and high protection rate against different challenge doses of cholera strains. Our findings demonstrate that chitosan and alginate salt are superior adjuvants for boosting the KCV immune response and highlights the requirement for further vaccine development.<\/jats:p>","DOI":"10.1002\/jbm.a.37240","type":"journal-article","created":{"date-parts":[[2021,6,12]],"date-time":"2021-06-12T06:36:30Z","timestamp":1623479790000},"page":"2462-2470","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Chitosan and alginate salt as biomaterials are potential natural adjuvants for killed cholera vaccine"],"prefix":"10.1002","volume":"109","author":[{"given":"Nourhan H.","family":"AbdelAllah","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Pharmacy Beni\u2010Suef University  Beni\u2010Suef Egypt"},{"name":"Viral Control Unit Egyptian Drug Authority (EDA)  Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasser","family":"Gaber","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Pharmacy Beni\u2010Suef University  Beni\u2010Suef Egypt"},{"name":"Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy Mutah University  Al\u2010karak Jordan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3999-2839","authenticated-orcid":false,"given":"Sameh","family":"AbdelGhani","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Pharmacy Beni\u2010Suef University  Beni\u2010Suef Egypt"},{"name":"Department of Medicine School of Medicine, University of Louisville  Louisville Kentucky USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed E.","family":"Rashed","sequence":"additional","affiliation":[{"name":"Microbiology Department Egyptian Drug Authority (EDA)  Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmed F.","family":"Azmy","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Pharmacy Beni\u2010Suef University  Beni\u2010Suef Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,6,11]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/polym11111837"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-6446(03)02864-2"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.589833"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3409"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0900164"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2510"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2013.07.081"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2020.02.287"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/7659684"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2010.09.058"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2018.08.054"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.02.004"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2008.12.003"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.4161\/hv.4.2.5122"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2017.09.034"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/169.1.230"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1128\/iai.65.9.3571-3576.1997"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2008.79.708"},{"key":"e_1_2_8_20_1","first-page":"CD000974","article-title":"Vaccines for preventing cholera: killed whole cell or other subunit vaccines (injected)","volume":"8","author":"Graves PM","year":"2010","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiy414"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpb.2011.06.009"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0002683"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0003881"},{"key":"e_1_2_8_25_1","volume-title":"AVMA Guidelines for the Euthanasia of Animals: 2013 edition","author":"Underwood W","year":"2013"},{"key":"e_1_2_8_26_1","unstructured":"World Health Organization.Active mouse protection test of cholera vaccine. 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