Abstract
BackgroundZika virus (ZIKV) has been declared a public health emergency that requires development of an effective vaccine, as it might represent an international threat.MethodsHere, two novel DNA-based (pVAXzenv) and fowlpox-based (FPzenv) recombinant putative vaccine candidates were constructed that contained the cPrME genes of ZIKV. The env gene inserted into the fowlpox vector was verified for correct transgene expression by Western blotting and by immunofluorescence in different cell lines. The production of virus-like particles as a result of env gene expression was also demonstrated by electron microscopy. BALB/c mice were immunosuppressed with dexamethasone and immunized following a prime–boost strategy in a heterologous protocol where pVAXzenv was followed by FPzenv, to evaluate the immunogenicity of the Env protein. The mice underwent a challenge with an epidemic ZIKV after the last boost.ResultsThese data show that the ZIKV Env protein was correctly expressed in both normal human lung fibroblasts (MRC-5 cells) and green monkey kidney (Vero) cells infected with FPzenv, and that the transgene expression lasted for more than 2 weeks. After mucosal administration of FPzenv, the immunized mice showed specific and significantly higher humoral responses compared to the control mice. However, virus neutralizing antibodies were not detected using plaque reduction assays.ConclusionsAlthough BALB/c mice appear to be an adequate model for ZIKV infection, as it mimics the natural mild infection in human beings, inadequate immune suppression seemed to occur by dexamethasone and different immune suppression strategies should be applied before challenge to reveal any protection of the mice.
Highlights
Zika virus (ZIKV) has been declared a public health emergency that requires development of an effective vaccine, as it might represent an international threat
We report on the construction of a novel DNA recombinant and a novel FP recombinant (FPzenv) putative vaccines that contain the cPrME genes of ZIKV (Fig. 1). This sequence is related to cellular entry, and we evaluate the immunogenicity of the Env protein in a mouse model after challenge with an epidemic ZIKV strain
A band of 54 kDa was always seen (Fig. 2a, lanes 4), which was present when the Vero cells were infected with ZIKV (Fig. 2a, lanes 2) as the positive control, both when recognized by the mouse monoclonal antibody and the rabbit polyclonal antibodies
Summary
Zika virus (ZIKV) has been declared a public health emergency that requires development of an effective vaccine, as it might represent an international threat. Human infections were initially reported in Nigeria in 1954 [7], but the first major outbreak occurred in 2007 on Yap Island, in the Federated States of Micronesia, where almost 75% of the population was shown to be infected, and almost 20% developed symptomatic disease [8]. ZIKV infections are mainly asymptomatic, but in spite of the generally mild self-limiting symptoms associated with maculopapular rash, headache, conjunctivitis, and musculoskeletal pain, neurological complications can occur, such as microcephaly in the developing fetus [4]. ZIKV has been associated with Guillain-Barré syndrome in adults, an autoimmune neurological disease that is characterized by muscle weakness, motor dysfunction, and in some cases, paralysis [10, 11], as the virus can infect human neural progenitor cells [12]
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