{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:06:27Z","timestamp":1791223587928,"version":"4.1.0"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2014,2,1]],"date-time":"2014-02-01T00:00:00Z","timestamp":1391212800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Shigella is one of the leading pathogens contributing to the vast pediatric diarrheal disease burden in low-income countries. No licensed vaccine is available, and the existing candidates are only partially effective and serotype specific. Shigella type III secretion system proteins IpaB and IpaD, which are conserved across Shigella spp., are candidates for a broadly protective, subunit-based vaccine. In this study, we investigated the immunogenicity and protective efficacy of IpaB and IpaD administered intradermally (i.d.) with a double-mutant of the Escherichia coli heat-labile enterotoxin (dmLT) adjuvant using microneedles. Different dosage levels of IpaB and IpaD, with or without dmLT, were tested in mice. Vaccine delivery into the dermis, recruitment of neutrophils, macrophages, dendritic cells, and Langerhans cells, and colocalization of vaccine Ag within skin-activated APC were demonstrated through histology and immunofluorescence microscopy. Ag-loaded neutrophils, macrophages, dendritic cells, and Langerhans cells remained in the tissue at least 1 wk. IpaB, IpaD, and dmLT-specific serum IgG- and IgG-secreting cells were produced following i.d. immunization. The protective efficacy was 70% against Shigella flexneri and 50% against Shigella sonnei. Similar results were obtained when the vaccine was administered intranasally, with the i.d. route requiring 25\u201340 times lower doses. Distinctively, IgG was detected in mucosal secretions; secretory IgA, as well as mucosal and systemic IgA Ab-secreting cells, were seemingly absent. Vaccine-induced T cells produced IFN-\u03b3, IL-2, TNF-\u03b1, IL-17, IL-4, IL-5, and IL-10. These results demonstrate the potential of i.d. vaccination with IpaB and IpaD to prevent Shigella infection and support further studies in humans.<\/jats:p>","DOI":"10.4049\/jimmunol.1302743","type":"journal-article","created":{"date-parts":[[2014,1,23]],"date-time":"2014-01-23T04:55:34Z","timestamp":1390452934000},"page":"1630-1640","source":"Crossref","is-referenced-by-count":54,"title":["Intradermal Delivery of <i>Shigella<\/i> IpaB and IpaD Type III Secretion Proteins: Kinetics of Cell Recruitment and Antigen Uptake, Mucosal and Systemic Immunity, and Protection across Serotypes"],"prefix":"10.1093","volume":"192","author":[{"given":"Shannon J","family":"Heine","sequence":"first","affiliation":[{"name":"Center for Vaccine Development, University of Maryland School of Medicine , Baltimore, MD 21201"},{"name":"Department of Pediatrics, University of Maryland School of Medicine , Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jovita","family":"Diaz-McNair","sequence":"additional","affiliation":[{"name":"Center for Vaccine Development, University of Maryland School of Medicine , Baltimore, MD 21201"},{"name":"Department of Pediatrics, University of Maryland School of Medicine , Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhay U","family":"Andar","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences Department, University of Maryland School of Pharmacy , Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cinthia B","family":"Drachenberg","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Maryland School of Medicine , Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lillian","family":"van de Verg","sequence":"additional","affiliation":[{"name":"Enteric Vaccine Initiative, PATH , Washington, DC 20001"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Walker","sequence":"additional","affiliation":[{"name":"Enteric Vaccine Initiative, PATH , Washington, DC 20001"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy L","family":"Picking","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, Oklahoma State University , Stillwater, OK 74078"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcela F","family":"Pasetti","sequence":"additional","affiliation":[{"name":"Center for Vaccine Development, University of Maryland School of Medicine , Baltimore, MD 21201"},{"name":"Enteric Vaccine Initiative, PATH , Washington, DC 20001"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,2,15]]},"reference":[{"key":"2025032404140538200_r1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S0140-6736(13)60844-2","article-title":"Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study","volume":"382","author":"Kotloff","year":"2013","journal-title":"Lancet"},{"key":"2025032404140538200_r2","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1016\/S0140-6736(12)61728-0","article-title":"Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010","volume":"380","author":"Lozano","year":"2012","journal-title":"Lancet"},{"key":"2025032404140538200_r3","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.1016\/S0140-6736(12)61689-4","article-title":"Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010","volume":"380","author":"Murray","year":"2012","journal-title":"Lancet"},{"key":"2025032404140538200_r4","doi-asserted-by":"crossref","first-page":"3865","DOI":"10.1016\/j.vaccine.2006.03.039","article-title":"Enteric infections and the vaccines to counter them: future directions","volume":"24","author":"Levine","year":"2006","journal-title":"Vaccine"},{"key":"2025032404140538200_r5","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/nrgastro.2013.12","article-title":"Progress and pitfalls in Shigella vaccine research","volume":"10","author":"Barry","year":"2013","journal-title":"Nat. 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