{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:52:38Z","timestamp":1781110358784,"version":"3.54.1"},"reference-count":66,"publisher":"National Academy of Sciences","issue":"7","license":[{"start":{"date-parts":[[2021,8,8]],"date-time":"2021-08-08T00:00:00Z","timestamp":1628380800000},"content-version":"vor","delay-in-days":181,"URL":"https:\/\/www.pnas.org\/site\/aboutpnas\/licenses.xhtml"}],"funder":[{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"publisher","award":["CC30430"],"award-info":[{"award-number":["CC30430"]}],"id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R01-AI-042347"],"award-info":[{"award-number":["R01-AI-042347"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome","doi-asserted-by":"publisher","award":["218443\/Z\/19\/Z"],"award-info":[{"award-number":["218443\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["PGSD3-487259-2016"],"award-info":[{"award-number":["PGSD3-487259-2016"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2021,2,16]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    Two major serotypes of\n                    <jats:italic>Vibrio cholerae<\/jats:italic>\n                    circulate globally and cause pandemic cholera, but how infection or vaccination with each serotype impacts immune responses and subsequent protection against future infection by the pathogen is not well-known. We engineered matched serotype variants of a new oral cholera vaccine candidate, HaitiV, to investigate the effect of serotype variation on vaccine immunogenicity and protective efficacy. Our results provide a rigorous framework for oral bacterial vaccine evaluation in vivo and illuminate how serotype influences oral cholera vaccine potency, a finding of significant translational interest.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2018032118","type":"journal-article","created":{"date-parts":[[2021,2,8]],"date-time":"2021-02-08T19:11:44Z","timestamp":1612811504000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":14,"title":["Dissecting serotype-specific contributions to live oral cholera vaccine efficacy"],"prefix":"10.1073","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2378-3039","authenticated-orcid":false,"given":"Brandon","family":"Sit","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Brigham and Women\u2019s Hospital, Boston, MA 02115;"},{"name":"Department of Microbiology, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1737-5090","authenticated-orcid":false,"given":"Bolutife","family":"Fakoya","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Brigham and Women\u2019s Hospital, Boston, MA 02115;"},{"name":"Department of Microbiology, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1899-590X","authenticated-orcid":false,"given":"Ting","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Brigham and Women\u2019s Hospital, Boston, MA 02115;"},{"name":"Department of Microbiology, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3330-8023","authenticated-orcid":false,"given":"Gabriel","family":"Billings","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Brigham and Women\u2019s Hospital, Boston, MA 02115;"},{"name":"Department of Microbiology, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1843-7000","authenticated-orcid":false,"given":"Matthew K.","family":"Waldor","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Brigham and Women\u2019s Hospital, Boston, MA 02115;"},{"name":"Department of Microbiology, Harvard Medical School, Boston, MA 02115;"},{"name":"Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA 02115;"},{"name":"Howard Hughes Medical Institute, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2021,2,8]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)30559-7"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0003832"},{"key":"e_1_3_4_3_2","volume-title":"Ending cholera\u2014A global roadmap to 2030","author":"Global Task Force on Cholera Control","year":"2017","unstructured":"Global Task Force on Cholera Control, Ending cholera\u2014A global roadmap to 2030 (World Health Organization, 2017)."},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(17)30359-6"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0006376"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1510330"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(18)30284-5"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(18)30602-9"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1431769100"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00438-06"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jix253"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1080\/14760584.2017.1291348"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60436-X"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10392"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad5901"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aao2136"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1012928"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0818-3"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiy414"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0022172400032265"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1993.1046"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/0008-6215(94)84231-0"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0005044"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.03339-19"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1086\/341206"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jir416"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.7.2566"},{"key":"e_1_3_4_28_2","first-page":"43","article-title":"Contributions to the knowledge of Vibrio cholerae. 3. Immunological studies upon the types of Vibrio cholerae","volume":"2","author":"Nobechi K.","year":"1923","unstructured":"K. Nobechi, Contributions to the knowledge of Vibrio cholerae. 3. Immunological studies upon the types of Vibrio cholerae. Sci. Rep. Inst. Inf. Dis. Tokyo Govt. 2, 43\u201388 (1923).","journal-title":"Sci. Rep. Inst. Inf. Dis. Tokyo Govt."},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(67)92542-1"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.4103\/0970-0218.84142"},{"key":"e_1_3_4_31_2","first-page":"186","article-title":"Serotype variation in Vibrio cholerae El Tor diarrhoea in northern Nigeria","volume":"37","author":"Onyemelukwe G. C.","year":"1991","unstructured":"G. C. Onyemelukwe, R. V. Lawande, Serotype variation in Vibrio cholerae El Tor diarrhoea in northern Nigeria. Cent. Afr. J. Med. 37, 186\u2013189 (1991).","journal-title":"Cent. Afr. J. Med."},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0108521"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2011.06.121"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2018.1504155"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2020.10.043"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aap8423"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0007417"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00232-20"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0011558"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.64.10.4373-4377.1996"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.2.977-981.2000"},{"key":"e_1_3_4_42_2","first-page":"195","volume-title":"Cholera and Related Diarrheas. Molecular Aspects of a Global Health Problem","author":"Levine M. M.","year":"1980","unstructured":"M. M. Levine, \u201cImmunity to cholera as evaluated in volunteers\u201d in Cholera and Related Diarrheas. Molecular Aspects of a Global Health Problem, \u00d6. Ouchterlony, J. Holmgren, Eds. (43rd Nobel Symposium, Karger, Basel, Switzerland, 1980), pp. 195\u2013203."},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0003881"},{"key":"e_1_3_4_44_2","first-page":"618","article-title":"Sur certaines proprietes du bacille cholerique en rapport avec l\u2019immunite","volume":"81","author":"Kabeshima T.","year":"1918","unstructured":"T. Kabeshima, Sur certaines proprietes du bacille cholerique en rapport avec l\u2019immunite. C. R. Soc. Biol. 81, 618 (1918).","journal-title":"C. R. Soc. Biol."},{"key":"e_1_3_4_45_2","first-page":"327","article-title":"A serological survey for cholear antibodies in rural east Pakistan. 1. The distribution of antibody in the control population of a cholera-vaccine field-trial area and the relation of antibody titre to the pattern of endemic cholera","volume":"38","author":"Mosley W. H.","year":"1968","unstructured":"W. H. Mosley, A. S. Benenson, R. Barui, A serological survey for cholear antibodies in rural east Pakistan. 1. The distribution of antibody in the control population of a cholera-vaccine field-trial area and the relation of antibody titre to the pattern of endemic cholera. Bull. World Health Organ. 38, 327\u2013334 (1968).","journal-title":"Bull. World Health Organ."},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciw145"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/0035-9203(79)90119-6"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00626-16"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40168-019-0746-y"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.05.036"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiaa358.10.1093\/infdis\/jiaa358"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aap8775"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2020.04.008"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.3109\/00365540903289688"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1098\/rspb.2006.3668"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-13-173"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.11604\/pamj.2020.35.32.18853"},{"key":"e_1_3_4_58_2","first-page":"117","article-title":"Note on the relationship of the so-called Ogawa and Inaba types of V. cholerae","volume":"35","author":"Shrivastava D.","year":"1947","unstructured":"D. Shrivastava, P. White, Note on the relationship of the so-called Ogawa and Inaba types of V. cholerae. Indian J. Med. Res. 35, 117\u2013129 (1947).","journal-title":"Indian J. Med. Res."},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.99.3.688-695.1969"},{"key":"e_1_3_4_60_2","first-page":"3","article-title":"The utility of human challenge studies in vaccine development: Lessons learned from cholera","volume":"2011","author":"Shirley D.-A. T.","year":"2011","unstructured":"D.-A. T. Shirley, M. A. McArthur, The utility of human challenge studies in vaccine development: Lessons learned from cholera. Vaccine (Auckl.) 2011, 3\u201313 (2011).","journal-title":"Vaccine (Auckl.)"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00189-16"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00799-10"},{"key":"e_1_3_4_63_2","first-page":"17","article-title":"Cholera outbreaks in the El Tor biotype era and the impact of the new El Tor variants","volume":"379","author":"Mukhopadhyay A. K.","year":"2014","unstructured":"A. K. Mukhopadhyay, Y. Takeda, G. Balakrish Nair, Cholera outbreaks in the El Tor biotype era and the impact of the new El Tor variants. Curr. Top. Microbiol. Immunol. 379, 17\u201347 (2014).","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"e_1_3_4_64_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0008128"},{"key":"e_1_3_4_65_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.8.3733-3739.1999"},{"key":"e_1_3_4_66_2","volume-title":"Guide for the Care and Use of Laboratory Animals","author":"National Research Council","year":"2011","unstructured":"National Research Council, Guide for the Care and Use of Laboratory Animals (National Academies Press, Washington, DC, ed. 8, 2011).","edition":"8"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.2018032118","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2018032118","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T06:10:59Z","timestamp":1649830259000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.2018032118"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,8]]},"references-count":66,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2021,2,16]]}},"alternative-id":["10.1073\/pnas.2018032118"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2018032118","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.08.20.259119","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,8]]},"assertion":[{"value":"2021-02-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2018032118"}}