3.8 Review

Harnessing Recent Advances in Synthetic DNA and Electroporation Technologies for Rapid Vaccine Development Against COVID-19 and Other Emerging Infectious Diseases

Journal

FRONTIERS IN MEDICAL TECHNOLOGY
Volume 3, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fmedt.2021.640964

Keywords

dengue virus; DNA vaccines; prime-boost immunization; dengue envelope protein; dengue non-structural proteins

Funding

  1. Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro (FAPERJ) [E-26/010.001959/2019]
  2. National Institute of Science and Technology in Vaccines (INCTV) [573547/2013]
  3. Coordination of Improvement of Higher Education Personnel (CAPES) [88882.332560/2019-01]
  4. Brazilian National Research Council (CNPq) [310361/2019-2]

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Dengue virus infections continue to pose a significant threat to public health systems in tropical and subtropical regions, with the currently available Dengvaxia vaccine facing challenges. Recent research suggests that DNA vaccines could be a promising approach in combating dengue virus infections.
Dengue infections still have a tremendous impact on public health systems in most countries in tropical and subtropical regions. The disease is systemic and dynamic with broad range of manifestations, varying from mild symptoms to severe dengue (Dengue Hemorrhagic Fever and Dengue Shock Syndrome). The only licensed tetravalent dengue vaccine, Dengvaxia, is a chimeric yellow fever virus with prM and E genes from the different dengue serotypes. However, recent results indicated that seronegative individuals became more susceptible to develop severe dengue when infected after vaccination, and now WHO recommends vaccination only to dengue seropositive people. One possibility to explain these data is the lack of robust T-cell responses and antibody-dependent enhancement of virus replication in vaccinated people. On the other hand, DNA vaccines are excellent inducers of T-cell responses in experimental animals and it can also elicit antibody production. Clinical trials with DNA vaccines have improved and shown promising results regarding the use of this approach for human vaccination. Therefore, in this paper we review preclinical and clinical tests with DNA vaccines against the dengue virus. Most of the studies are based on the E protein since this antigen is the main target for neutralizing antibody production. Yet, there are other reports with DNA vaccines based on non-structural dengue proteins with protective results, as well. Combining structural and non-structural genes may be a solution for inducing immune responses aging in different infection moments. Furthermore, DNA immunizations are also a very good approach in combining strategies for vaccines against dengue, in heterologous prime/boost regimen or even administering different vaccines at the same time, in order to induce efficient humoral and cellular immune responses.

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