Recently, Zika virus (ZIKV) outbreak has been associated with a sharp increase in cases of Guillain–Barré syndrome and severe fetal abnormalities. However, the mechanism underlying the interaction of ZIKV with host cells is not yet clear. Axl, a receptor tyrosine kinase, is postulated as a receptor for ZIKV entry; however, its in vivo role during ZIKV infection and its impact on the outcome of the disease have not been fully characterized and evaluated. Moreover, there are contradictory results on its involvement in ZIKV infection. Here we utilized Axl-deficient mice (Axl−/−) and their littermates (Axl+/−) to study the in vivo role of Axl in ZIKV infection. Our results showed that both Axl+/− and Axl−/− suckling mice supported the replication of ZIKV and presented clinical manifestations. No significant difference has been found between Axl-deficient mice and their littermates in terms of the survival rate, clinical manifestations, viral load, ZIKV distribution and histopathological changes in major organs. These results therefore indicate that Axl is not an indispensable factor for ZIKV infection in mice.

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Both Zika virus (ZIKV) and four serotypes of dengue virus (DENV1–4) are antigenically related mosquito-borne flaviviruses that co-circulate in overlapping geographic distributions. The considerable amino acid sequence homology and structural similarities between ZIKV and DENV1–4 may be responsible for the complicated immunological cross-reactivity observed for these viruses. Thus, a successful Zika vaccine needs to not only confer protection from ZIKV infection but must also be safe during secondary exposures with other flavivirus, especially DENVs. In this study, we used a Zika DNA vaccine candidate (pV-ZME) expressing the ZIKV premembrane and envelop proteins to immunize BALB/c mice and evaluated the potential cross-reactive immune responses to DENV1–4. We observed that three doses of the pV-ZME vaccine elicited the production of cross-reactive antibodies, cytokines and CD8 + T cell responses and generated cross-protection against DENV1–4. Our results demonstrate a novel approach for design and development of safe Zika and/or dengue vaccines.

The development of a safe and effective tetravalent dengue vaccine that elicits protection against all dengue virus (DENV) serotypes is urgently needed. The consensus sequence of the ectodomain of envelope (E) protein of DENV (cE80) has been examined as an immunogen previously. In the current study, a cE80 DNA (D) vaccine was constructed and evaluated in conjunction with the cE80 protein (P) vaccine to examine whether both vaccines used together can further improve the immune responses. The cE80 DNA vaccine was administrated using either a homologous (DNA alone, DDD) or heterologous (DNA prime-protein boost: DDP or DPP) regimen, and evaluated for immunogenicity and protective efficacy in mice. Among the three DNA-based immunization regimens tested, DDP immunization is the optimal immunization regimen that elicited the greatest systemic immune response and conferred protection against all four DENV serotypes. This work provides innovative ideas for the development of consensus E-based dengue vaccines and the testing of optimal immunization regimens.

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.

Dengue virus (DV) is the causal pathogen of dengue fever, which is one of the most rapidly spread mosquito-borne disease worldwide and has become a severe public health problem. Currently, there is no specific treatment for dengue; thus, a vaccine would be an effective countermeasure to reduce the morbidity and mortality. Although, the chimeric Yellow fever dengue tetravalent vaccine has been approved in some countries, it is still necessary to develop safer, more effective, and less costly vaccines. In this study, a DNA vaccine candidate pVAX1-D1ME expressing the prME protein of DV1 was inoculated in BALB/c mice via intramuscular injection or electroporation, and the immunogenicity and protection were evaluated. Compared with traditional intramuscular injection, administration with 50 μg pVAX1-D1ME via electroporation with three immunizations induced persistent humoral and cellular immune responses and effectively protected mice against lethal DV1 challenge. In addition, immunization with a bivalent vaccine consisting of pVAX1-D1ME and pVAX1-D2ME via electroporation generated a balanced IgG response and neutralizing antibodies against DV1 and DV2 and could protect mice from lethal challenge with DV1 and DV2. This study sheds new light on developing a dengue tetravalent DNA vaccine.

Dengue fever, caused by dengue viruses (DENVs), is a widespread mosquito-borne zoonotic disease; however, there is no available anti-dengue vaccine for worldwide use. In the current study, a DNA vaccine candidate (pV-D4ME) expressing prM-E protein of DENV serotype 4 (DENV-4) was constructed, and its immunogenicity and protection were evaluated in immunocompetent BALB/c mice. The pV-D4ME candidate vaccine induced effective humoral and cellular immunity of mice against DENV-4 in vivo when administered both at 50 lg and 5 lg through electroporation. Two weeks after receiving three immunizations, both doses of pV-D4ME DNA were shown to confer effective protection against lethal DENV-4 challenge. Notably, at 6 months after the three immunizations, 50 lg, but not 5 lg, of pV-D4ME could provide stable protection (100% survival rate) against DENV-4 lethal challenge without any obvious clinical signs. These results suggest that immunization with 50 lg pV-D4ME through electroporation could confer effective and long-term protection against DENV-4, offering a promising approach for development of a novel DNA vaccine against DENVs.