Live Zika virus chimeric vaccine candidate based on a yellow fever 17-D attenuated backbone

Touret, Franck; Gilles, Magali; Klitting, Raphaëlle; Aubry, Fabien; Lamballerie, Xavier de; Nougairède, Antoine

doi:10.1101/272625

Cited by 6 publications

(5 citation statements)

References 36 publications

(3 reference statements)

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“…Therefore, different immune suppression strategies should be applied to reveal any protection before challenge as well as other animal models. Interferon-receptor-deficient immunocompromised mice can represent another strategy, by using AG129 Ifnαr1-/-mice, which lack receptors for both type I (α/β) and type II (γ) interferons [67], or mice treated with antibodies against interferon.…”

Section: Resultsmentioning

confidence: 99%

Construction of a recombinant avipoxvirus expressing the env gene of Zika virus as a novel putative preventive vaccine

Zanotto

Paolini²,

Radaelli

et al. 2021

Virol J

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Background Zika virus (ZIKV) has been declared a public health emergency that requires development of an effective vaccine, as it might represent an international threat. Methods Here, 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. Results These 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. Conclusions Although 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.

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Section: Resultsmentioning

confidence: 99%

Construction of a recombinant avipoxvirus expressing the env gene of Zika virus as a novel putative preventive vaccine

Zanotto

Paolini²,

Radaelli

et al. 2021

Virol J

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“…In the case of SARS-CoV-2 and FeCoV, we conveniently obtained the rescued viruses under standard operating conditions and showed that their genomic sequence and characteristics in terms of growth and production of cytopathic effect were those of the original "natural" strains. In previous studies, we demonstrated the capacity of the ISA method to generate modi ed DNA fragments to analyse the phenotypic effects of engineered sequences 21,22 .…”

Section: Discussionmentioning

confidence: 99%

Infectious Subgenomic Amplicons method to expedite reverse genetics of SARS-CoV-2 and other coronaviruses

Mélade¹,

Piorkowski

Touret

et al. 2020

Preprint

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There is a need for simple reverse genetics methods to decipher the biological properties of animal and human coronaviruses. Here, we attempted to rescue the recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the Feline enteric coronavirus (FeCoV) using the rapid “Infectious-Subgenomic Amplicons” (ISA) method. For each virus, transfection into permissive cells of eight overlapping subgenomic cDNA fragments covering the entire genome allowed reconstruction of the complete virus genome and generated infectious viral particles. Rescued viruses replicated the phenotypic and genotypic characteristics of the original isolates. In conclusion, the ISA method, which had been previously used for RNA viruses with shorter genomes (e.g., flaviviruses, alphaviruses and enteroviruses) can be used to rescue viruses with substantially longer genomes and usefully complements pre-existing methods for reverse genetics of coronaviruses. Its extreme simplicity and versatility makes it a strong option to decipher the biological properties of coronaviruses circulating in human, domestic or wild fauna populations.

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“…The 10.8 kb genome of ZIKV encodes a single polyprotein that, upon action of host and viral proteases, forms three structural proteins (C, PrM, and E) and seven nonstructural proteins (NS1-5 NS2A, NS2B, NS3, NS4A, NS4B, and NS5) (Ye et al, 2016). Numerous approaches are being employed to develop live attenuated virus (Shan et al, 2017), inactivated whole virus (Sumathy et al, 2017), subunit DNA/RNA vaccines (Pardi et al, 2017;To et al, 2018), virus like particles (Espinosa et al, 2018;Salvo et al, 2018), over virus vectored (Xu et al, 2018), and chimeric ZIKV (Kum et al, 2018;Li et al, 2018) vaccines pertaining to several benefits including economical and long-term immunity. But only a few of them have generated appropriate prophylactic responses in tested in vivo models.…”

Section: Chimeric Zika Virusmentioning

confidence: 99%

“…Another chimeric virus, CH-17-D/ZIKV, comprising prM/E proteins of ZIKV strain integrated into yellow fever virus 17-D attenuated backbone was constructed by Touret et al (2018). Using Infectious Subgenomic Amplicons (ISA) reverse genetics methods, cleavage site between prepeptide and prM protein was modified.…”

Section: Figmentioning

confidence: 99%

Next generation agents (synthetic agents): Emerging threats and challenges in detection, protection, and decontamination

Sharma

Gupta

Ahmad

et al. 2020

Handbook on Biological Warfare Preparedness

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Live Zika virus chimeric vaccine candidate based on a yellow fever 17-D attenuated backbone

Abstract: 11Zika virus (ZIKV) recently dispersed throughout the tropics and sub-tropics causing 12 epidemics associated with congenital disease and neurological complications.

Cited by 6 publications

References 36 publications

Construction of a recombinant avipoxvirus expressing the env gene of Zika virus as a novel putative preventive vaccine

Construction of a recombinant avipoxvirus expressing the env gene of Zika virus as a novel putative preventive vaccine

Infectious Subgenomic Amplicons method to expedite reverse genetics of SARS-CoV-2 and other coronaviruses

Next generation agents (synthetic agents): Emerging threats and challenges in detection, protection, and decontamination

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