A VSV-based Zika virus vaccine protects mice from lethal challenge

Emanuel, Jackson; Callison, Julie; Dowd, Kimberly A.; Pierson, Theodore C.; Feldmann, Heinz; Marzi, Andrea

doi:10.1038/s41598-018-29401-x

Cited by 68 publications

(67 citation statements)

References 66 publications

(64 reference statements)

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“…53 Replicationcompetent recombinant VSVs (VSV-EBOV-sHAzip, VSV-sHAzip-EBOV, VSV-sHA-EBOV, VSV-EBOV-HAfl, and VSV-HAfl) were generated as described previously. 24 The complete sequence of the VSV vaccines was confirmed by Sanger sequencing. Detailed sequence information can be obtained from the authors upon request.…”

Section: Plasmid Construction and Vsv Recoverymentioning

confidence: 99%

“…21 The VSV platform used here is based on the attenuated replication-competent vaccine that produces a rapid and robust immune response to foreign antigens after a single immunization and has been shown to protect against numerous pathogens. [22][23][24][25][26] Especially, the VSV-based Ebola virus (EBOV) vaccine, VSV-EBOV (also known as rVSV-ZEBOV or Ervebo), which expresses the EBOV GP instead of the VSV GP, is considered safe and highly immunogenic based on data from multiple clinical trials. 27,28 Noteworthy, VSV-EBOV has shown promising efficacy against EBOV in a phase III clinical trial 28 and is currently being used in the Democratic Republic of the Congo during the ongoing EBOV outbreak.…”

Section: Introductionmentioning

confidence: 99%

“…30 The feasibility of this concept has previously been demonstrated in preclinical studies with vaccines for influenza (HPAI virus), flavi-(Zika virus), and bunyaviruses (Andes virus). 24,[31][32][33] In this study, we designed and tested different VSV-EBOV-based vaccine vectors expressing different versions of the H5N1 HA (A/Vietnam/1203/2004 (VN/1203)) to demonstrate the feasibility of the platform for a fast-acting pan-H5 vaccine. Mice were vaccinated with a single dose or prime/boost regimen of the different vaccine candidates and challenged with a lethal dose of homologous H5N1 virus.…”

Section: Introductionmentioning

confidence: 99%

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A single dose of a vesicular stomatitis virus-based influenza vaccine confers rapid protection against H5 viruses from different clades

et al. 2020

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The avian influenza virus outbreak in 1997 highlighted the potential of the highly pathogenic H5N1 virus to cause severe disease in humans. Therefore, effective vaccines against H5N1 viruses are needed to counter the potential threat of a global pandemic. We have previously developed a fast-acting and efficacious vaccine against Ebola virus (EBOV) using the vesicular stomatitis virus (VSV) platform. In this study, we generated recombinant VSV-based H5N1 influenza virus vectors to demonstrate the feasibility of this platform for a fast-acting pan-H5 influenza virus vaccine. We chose multiple approaches regarding antigen design and genome location to define a more optimized vaccine approach. After the VSV-based H5N1 influenza virus constructs were recovered and characterized in vitro, mice were vaccinated by a single dose or prime/boost regimen followed by challenge with a lethal dose of the homologous H5 clade 1 virus. We found that a single dose of VSV vectors expressing full-length hemagglutinin (HAfl) were sufficient to provide 100% protection. The vaccine vectors were fast-acting as demonstrated by uniform protection when administered 3 days prior to lethal challenge. Moreover, single vaccination induced cross-protective H5-specific antibodies and protected mice against lethal challenge with various H5 clade 2 viruses, highlighting the potential of the VSV-based HAfl as a pan-H5 influenza virus emergency vaccine.npj Vaccines (2020) 5:4 ; https://doi.

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Section: Plasmid Construction and Vsv Recoverymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A single dose of a vesicular stomatitis virus-based influenza vaccine confers rapid protection against H5 viruses from different clades

et al. 2020

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“…Interestingly, vaccination with the vaccines was sufficient to also protect outbred CD1 mice from EBOV challenge. 123 In a study assessing multiple ZIKV antigens in a VSV vector, which was attenuated via a point mutation in the VSV L protein, combining the ZIKV prM and E proteins with the nonstructural NS1 protein showed robust humoral and cellular responses in immunocompetent mice, as well as protection from disease in IFNAR − / − mice. 124 Furthermore, a VSV vector expressing the ZIKV capsid protein was also shown to be immunogenic with dominating cellular immune responses and reduced viral replication in the spinal cord and brain tissues of immunocompetent mice.…”

Section: Mers-and Sars-coronavirusesmentioning

confidence: 99%

Recombinant vesicular stomatitis virus vector vaccines for WHO blueprint priority pathogens

Fathi

Dahlke

Addo

2019

Human Vaccines & Immunotherapeutics

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The devastating Ebola virus (EBOV) outbreak in West Africa in 2013-2016 has flagged the need for the timely development of vaccines for high-threat pathogens. To be better prepared for new epidemics, the WHO has compiled a list of priority pathogens that are likely to cause future outbreaks and for which R&D efforts are, therefore, paramount (R&D Blueprint: https://www.who.int/blueprint/priority-diseases/en/). To this end, the detailed characterization of vaccine platforms is needed. The vesicular stomatitis virus (VSV) has been established as a robust vaccine vector backbone for infectious diseases for well over a decade. The recent clinical trials testing the vaccine candidate VSV-EBOV against EBOV disease now have added a substantial amount of clinical data and suggest VSV to be an ideal vaccine vector candidate for outbreak pathogens. In this review, we discuss insights gained from the clinical VSV-EBOV vaccine trials as well as from animal studies investigating vaccine candidates for Blueprint pathogens. ARTICLE HISTORY

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“…In order to determine the protective efficacy of this hAd5-ZKV, we used a Ifnar1 -/lethal infection model that has been used to validate several ZIKV vaccines currently in phase I trials [67,68]. Using this model, we demonstrated that a single hAd5-ZKV vaccination is sufficient for providing protection against a lethal challenge within Ifnar1 -/mice, as well as reducing weight-loss, improving clinical scores, and preventing mortality.…”

Section: Discussionmentioning

confidence: 99%

Immunogenicity and Efficacy of a Recombinant Human Adenovirus Type 5 Vaccine against Zika Virus

et al. 2020

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Zika virus (ZIKV) is a significant public health concern due to the pathogen's ability to be transmitted by either mosquito bite or sexual transmission, allowing spread to occur throughout the world. The potential consequences of ZIKV infection to human health, specifically neonates, necessitates the development of a safe and effective Zika virus vaccine. Here, we developed an intranasal Zika vaccine based upon the replication-deficient human adenovirus serotype 5 (hAd5) expressing ZIKV pre-membrane and envelope protein (hAd5-ZKV). The hAd5-ZKV vaccine is able to induce both cell-mediated and humoral immune responses to ZIKV epitopes. Importantly, this vaccine generated CD8 + T cells specific for a dominant ZIKV T cell epitope and is shown to be protective against a ZIKV challenge by using a pre-clinical model of ZIKV disease. We also demonstrate that the vaccine expresses pre-membrane and envelope protein in a confirmation recognized by ZIKV experienced individuals. Our studies demonstrate that this adenovirus-based vaccine expressing ZIKV proteins is immunogenic and protective in mice, and it encodes ZIKV proteins in a conformation recognized by the human antibody repertoire.The development of a ZIKV vaccine is urgent due to the speed of ZIKV spread in susceptible populations, as well as the range of diseases caused by infection [5]. According to the World Health Organization (WHO), a majority of individuals who are infected with ZIKV are asymptomatic, but those with a mild clinical form of the disease report symptoms including fever, rash, conjunctivitis, and muscle and joint pain, all of which typically last less than a week. While these symptoms are rarely debilitating, complications of Zika virus disease can include Guillain-Barré syndrome. Zika-induced microcephaly and congenital abnormalities are generally classified as congenital Zika syndrome (CZS), which is also a potential complication in the developing fetuses of pregnant women [4,6-10]. These risks, combined with the explosive outbreaks that occurred at Yap Island in 2007 [11], French Polynesia in 2013 [12], and Brazil in 2015-16 [13], underscore the need to control the spread of ZIKV. However, there are no current FDA-approved vaccines available to control infection.Harnessing the power of both arms of the adaptive immune response improves vaccine potency and efficacy while reducing opportunities of viral escape. Current data from both naturally acquired human infection and mouse models of ZIKV disease indicate that protection from disease is multi-faceted (reviewed in [14][15][16][17][18]). Both small and large animal models of ZIKV infection have demonstrated that the Zika-specific CD8 + and CD4 + T cell response is necessary and sufficient to protect against a lethal ZIKV challenge [19][20][21][22]. As has been demonstrated previously for multiple flavivirus infections [23-25], ZIKV-specific polyclonal and monoclonal neutralizing antibody responses can protect mice and nonhuman primates from mortality and severe disease. There is also a role fo...

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A VSV-based Zika virus vaccine protects mice from lethal challenge

Cited by 68 publications

References 66 publications

A single dose of a vesicular stomatitis virus-based influenza vaccine confers rapid protection against H5 viruses from different clades

A single dose of a vesicular stomatitis virus-based influenza vaccine confers rapid protection against H5 viruses from different clades

Recombinant vesicular stomatitis virus vector vaccines for WHO blueprint priority pathogens

Immunogenicity and Efficacy of a Recombinant Human Adenovirus Type 5 Vaccine against Zika Virus

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