Long-Term Protection Elicited by a DNA Vaccine Candidate Expressing the prM-E Antigen of Dengue Virus Serotype 3 in Mice

Abstract

Dengue virus (DENV) is the causative agent of dengue, and its incidence has increased 30-fold in the past five decades. Among the four cocirculating serotypes, DENV3 is associated with an increased number of severe infections and has become widespread. Vaccination is the mainstay of prevention in reducing disease burden. Previously, the protective efficacy of DNA vaccine candidates toward DENV1, 2, and 4 was confirmed in mice. In this study, a DNA vaccine candidate (pVAX1-D3ME) expressing the prM and E proteins of DENV3 was constructed, and then the immunogenicity and protection were assessed in mice to further develop a tetravalent dengue vaccine. Moreover, the cross-reactive immune responses against the other three serotypes were investigated. The results showed that three doses of 50 µg of pVAX1-D3ME were sufficient to induce strong antigen-specific T cell responses and robust and consistent neutralizing antibodies. Additionally, immunization with pVAX1-D3ME offered protective immunity against not only DENV3 but also the other three serotypes, which could be observed even after 12 months. This study shows great promise for the further evaluation of a dengue tetravalent DNA vaccine candidate in large animal models, including non-human primates.

An Intramuscular DNA Vaccine for SARS-CoV-2 Decreases Viral Lung Load but Not Lung Pathology in Syrian Hamsters

“…Further, pVax1 features a kanamycin resistance gene for selection to avoid allergic responses associated with ampicillin as well as a human CMV promoter and BGH polyadenylation signal for efficient DNA expression and mRNA transcription termination, respectively [ 18 ]. Recently, the vector has been used in platforms showing enhanced protection from Japanese Encephalitis Virus, influenza H9N2, Dengue virus, Crimean-Congo Hemorrhagic Fever Virus, and anti-tumor applications, [ 19 , 20 , 21 , 22 , 23 ]. These DNA vaccines were able to elicit high titers of protective antibody [ 19 , 20 , 21 , 22 ] suggesting this approach may also be effective for COVID-19.…”

“…Recently, the vector has been used in platforms showing enhanced protection from Japanese Encephalitis Virus, influenza H9N2, Dengue virus, Crimean-Congo Hemorrhagic Fever Virus, and anti-tumor applications, [ 19 , 20 , 21 , 22 , 23 ]. These DNA vaccines were able to elicit high titers of protective antibody [ 19 , 20 , 21 , 22 ] suggesting this approach may also be effective for COVID-19. Importantly, none of these studies reported negative side effects associated with use of the pVax1 vector [ 19 , 20 , 21 , 22 ].…”

Dengue Virus and Vaccines: How Can DNA Immunization Contribute to This Challenge?

“…Following these and other reports presenting promising results with monovalent prM/E-based pVAX constructions (99)(100)(101)(102), a new tetravalent formulation was developed by cloning sequences of Hawaii, Tr1751 strain, H87 and H241 strains from DENV1 to 4, respectively (TetraME) (78, 102). A 3-dose scheme of 50 µg of each monovalent DNA vaccine administered by electroporation in BALB/c mice induced T-cell activation with high IL-4 and IFN-γ production, long-term NAb response against all the four serotypes, and animals survived monovalent DENV1-4 challenges (78).…”

Yersinia pestis Plasminogen Activator

“…This information added with the fact that Pla is not an effective immunogen and is not a protective antigen in mice suggest that the absence of pla should not decrease the efficacy of a live plague vaccine while increasing its safety. Consistent with this idea, different vaccine strains were engineered [ 147 , 148 , 149 , 150 ]. One of them, lacking the Braun lipoprotein, the lipid A biosynthesis myristoyltransferase and Pla (i.e., a Δ lpp Δ msbB Δ pla strain), confers long-term humoral and cell-mediated immune responses and full protection against pneumonic plague in rats [ 149 ].…”