A single-dose live-attenuated vaccine prevents Zika virus pregnancy transmission and testis damage

Shan, Chao; Muruato, Antonio E.; Jagger, Brett W.; Richner, Justin M.; Nunes, Bruno Tardelli Diniz; Medeiros, Daniele B. A.; Xie, Xuping; Nunes, Jannyce G. C; Morabito, Kaitlyn M.; Kong, Wing-Pui; Pierson, Theodore C.; Barrett, Alan D.T.; Weaver, Scott C.; Rossi, Shannan L.; Vasconcelos, Pedro F. C.; Graham, Barney S.; Diamond, Michael S.; Shi, Pei–Yong

doi:10.1038/s41467-017-00737-8

Cited by 129 publications

(134 citation statements)

References 35 publications

(42 reference statements)

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“…To further address the impact of inflammasome activation on type I IFN signaling, we performed in vivo ZIKV infection in Nlrp3 −/− mice. According to previous work, 1‐day‐old neonatal mice were intracerebrally injected with ZIKV for 5 days (Manangeeswaran et al , ; Shan et al , ). The production of IL‐1β was significantly decreased in the brains of Nlrp3 −/− mice than that in WT mice (Fig H).…”

Section: Resultsmentioning

confidence: 99%

Zika virus elicits inflammation to evade antiviral response by cleaving cGAS via NS 1‐caspase‐1 axis

et al. 2018

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Viral infection triggers host innate immune responses, which primarily include the activation of type I interferon (IFN) signaling and inflammasomes. Here, we report that Zika virus (ZIKV) infection triggers NLRP3 inflammasome activation, which is further enhanced by viral non-structural protein NS1 to benefit its replication. NS1 recruits the host deubiquitinase USP8 to cleave K11-linked poly-ubiquitin chains from caspase-1 at Lys134, thus inhibiting the proteasomal degradation of caspase-1. The enhanced stabilization of caspase-1 by NS1 promotes the cleavage of cGAS, which recognizes mitochondrial DNA release and initiates type I IFN signaling during ZIKV infection. NLRP3 deficiency increases type I IFN production and strengthens host resistance to ZIKV and Taken together, our work unravels a novel antagonistic mechanism employed by ZIKV to suppress host immune response by manipulating the interplay between inflammasome and type I IFN signaling, which might guide the rational design of therapeutics in the future.

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Section: Resultsmentioning

confidence: 99%

Zika virus elicits inflammation to evade antiviral response by cleaving cGAS via NS 1‐caspase‐1 axis

et al. 2018

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“…Recently, several ZIKV vaccine candidates have been reported, including nucleic acid (DNA and mRNA), inactivated virus, subunit, VLP, vectored vaccines (including adenovirus and vaccinia virus), and live attenuated vaccines 17,19,[27][28][29][30][31][32][33][34] . These vaccine candidates triggered various degrees of humoral and cellular immunity and protection in rodent and/or nonhuman primate models.…”

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confidence: 99%

A Zika virus vaccine expressing premembrane-envelope-NS1 polyprotein

et al. 2018

Nat Commun

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Current efforts to develop Zika virus (ZIKV) subunit vaccines have been focused on pre-membrane (prM) and envelope (E) proteins, but the role of NS1 in ZIKV-specific immune response and protection is poorly understood. Here, we develop an attenuated recombinant vesicular stomatitis virus (rVSV)-based vaccine expressing ZIKV prM-E-NS1 as a polyprotein. This vectored vaccine candidate is attenuated in mice, where a single immunization induces ZIKV-specific antibody and T cell immune responses that provide protection against ZIKV challenge. Co-expression of prM, E, and NS1 induces significantly higher levels of Th2 and Th17 cytokine responses than prM-E. In addition, NS1 alone is capable of conferring partial protection against ZIKV infection in mice even though it does not induce neutralizing antibodies. These results demonstrate that attenuated rVSV co-expressing prM, E, and NS1 is a promising vaccine candidate for protection against ZIKV infection and highlights an important role for NS1 in ZIKV-specific cellular immune responses.

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“…LAVs undeniably represent the most effective class of vaccines ever developed. Based on the success of past LAVs, several LAV candidates targeting challenging pathogens such as Dengue virus [40], Japanese Encephalitis virus [41], West Nile virus [42], Zika virus [43], SARS [44], Malaria [45] or Ebola virus [46,47], have been designed and evaluated. For instance, in response to the Ebola virus disease outbreaks in Africa between 2013 and 2016, a recombinant vesicular stomatitis virus (VSV) expressing the envelope glycoprotein of Ebola virus was generated (VSV-EBOV).…”

Section: Live-attenuated Vaccinesmentioning

confidence: 99%

Humanized Mice for Live-Attenuated Vaccine Research: From Unmet Potential to New Promises

O'Connell

Douam

2020

Vaccines

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Live-attenuated vaccines (LAV) represent one of the most important medical innovations in human history. In the past three centuries, LAV have saved hundreds of millions of lives, and will continue to do so for many decades to come. Interestingly, the most successful LAVs, such as the smallpox vaccine, the measles vaccine, and the yellow fever vaccine, have been isolated and/or developed in a purely empirical manner without any understanding of the immunological mechanisms they trigger. Today, the mechanisms governing potent LAV immunogenicity and long-term induced protective immunity continue to be elusive, and therefore hamper the rational design of innovative vaccine strategies. A serious roadblock to understanding LAV-induced immunity has been the lack of suitable and cost-effective animal models that can accurately mimic human immune responses. In the last two decades, human-immune system mice (HIS mice), i.e., mice engrafted with components of the human immune system, have been instrumental in investigating the life-cycle and immune responses to multiple human-tropic pathogens. However, their use in LAV research has remained limited. Here, we discuss the strong potential of LAVs as tools to enhance our understanding of human immunity and review the past, current and future contributions of HIS mice to this endeavor.

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A single-dose live-attenuated vaccine prevents Zika virus pregnancy transmission and testis damage

Cited by 129 publications

References 35 publications

Zika virus elicits inflammation to evade antiviral response by cleaving cGAS via NS 1‐caspase‐1 axis

Zika virus elicits inflammation to evade antiviral response by cleaving cGAS via NS 1‐caspase‐1 axis

A Zika virus vaccine expressing premembrane-envelope-NS1 polyprotein

Humanized Mice for Live-Attenuated Vaccine Research: From Unmet Potential to New Promises

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