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It is believed that vaccines save at least 2\u20133\u00a0million lives per year worldwide. Smallpox has been eradicated and polio has almost disappeared worldwide through global vaccine campaigns. Most of the viral and bacterial infections that traditionally affected children have been drastically reduced thanks to national immunization programs in developed countries. However, many diseases are not yet preventable by vaccination, and vaccines have not been fully exploited for target populations such as elderly and pregnant women. This review focuses on the state of the art of recent clinical trials of vaccines for major unmet medical needs such as HIV, malaria, TB, and cancer. In addition, we describe the innovative technologies currently used in vaccine research and development including adjuvants, vectors, nucleic acid vaccines, and structure\u2010based antigen design. The hope is that thanks to these technologies, more diseases will be addressed in the 21st century by novel preventative and therapeutic vaccines.<\/jats:p>","DOI":"10.1002\/emmm.201403876","type":"journal-article","created":{"date-parts":[[2014,5,20]],"date-time":"2014-05-20T13:38:32Z","timestamp":1400593112000},"page":"708-720","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":408,"title":["Vaccines for the 21st century"],"prefix":"10.1038","volume":"6","author":[{"given":"Isabel","family":"Delany","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rino","family":"Rappuoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ennio","family":"De Gregorio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2014,5,6]]},"reference":[{"key":"BFEMMM201403876_CR1","doi-asserted-by":"crossref","first-page":"1863","DOI":"10.1056\/NEJMoa1102287","volume":"365","author":"ST Agnandji","year":"2011","unstructured":"Agnandji ST, Lell B, Soulanoudjingar SS, Fernandes JF, Abossolo BP, Conzelmann C, Methogo BG, Doucka Y, Flamen A, Mordmuller B et\u00a0al (2011) First results of phase 3 trial of RTS,S\/AS01 malaria vaccine in African children. 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