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Several studies indicate promising results in preclinical and clinical trials regarding immunization against ebola, human immunodeficiency virus (HIV), influenza, and human papillomavirus (HPV). The efficiency of nucleic acid vaccines has been highlighted in the fight against COVID-19 with unprecedented approval of their use in humans. However, their low intrinsic immunogenicity points to the need to use strategies capable of overcoming this characteristic and increasing the efficiency of vaccine campaigns. These strategies include the improvement of the epitopes\u2019 presentation to the system via MHC, the evaluation of immunodominant epitopes with high coverage against emerging viral subtypes, the use of adjuvants that enhance immunogenicity, and the increase in the efficiency of vaccine transfection. In this review, we provide updates regarding some characteristics, construction, and improvement of such vaccines, especially about the production of synthetic multi-epitope genes, widely employed in the current gene-based vaccines.<\/jats:p>","DOI":"10.3390\/genes13122287","type":"journal-article","created":{"date-parts":[[2022,12,5]],"date-time":"2022-12-05T03:38:38Z","timestamp":1670211518000},"page":"2287","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Third-Generation Vaccines: Features of Nucleic Acid Vaccines and Strategies to Improve Their Efficiency"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1786-3369","authenticated-orcid":false,"given":"Alanne Rayssa da Silva","family":"Melo","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Studies and Experimental Therapy\u2014LEMTE, Department of Genetics, Federal University of Pernambuco, Recife 50670-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1660-4901","authenticated-orcid":false,"given":"Larissa Silva","family":"de Mac\u00eado","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Studies and Experimental Therapy\u2014LEMTE, Department of Genetics, Federal University of Pernambuco, Recife 50670-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9360-1275","authenticated-orcid":false,"given":"Maria da Concei\u00e7\u00e3o Viana","family":"Inven\u00e7\u00e3o","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Studies and Experimental Therapy\u2014LEMTE, Department of Genetics, Federal University of Pernambuco, Recife 50670-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0715-8674","authenticated-orcid":false,"given":"Ingrid Andr\u00eassa","family":"de 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Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8341-7877","authenticated-orcid":false,"given":"Anna J\u00e9ssica Duarte","family":"Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Studies and Experimental Therapy\u2014LEMTE, Department of Genetics, Federal University of Pernambuco, Recife 50670-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4745-8919","authenticated-orcid":false,"given":"Marcus Vinicius de Arag\u00e3o","family":"Batista","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics and Biotechnology (GMBio), Department of Biology, Center for Biological and Health Sciences, Federal University of Sergipe, S\u00e3o Crist\u00f3v\u00e3o 49100-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4957-9549","authenticated-orcid":false,"given":"Antonio Carlos de","family":"Freitas","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Studies and Experimental Therapy\u2014LEMTE, Department of Genetics, Federal University of Pernambuco, Recife 50670-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,4]]},"reference":[{"key":"ref_1","first-page":"e02616","article-title":"Designing the Next Generation of Vaccines: Relevance for Future Pandemics","volume":"11","author":"Divangahi","year":"2020","journal-title":"mBio"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1016\/S0140-6736(16)31012-1","article-title":"Global, Regional, and National Life Expectancy, All-Cause Mortality, and Cause-Specific Mortality for 249 Causes of Death, 1980\u20132015: A Systematic Analysis for the Global Burden of Disease Study 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