A Zika Vaccine Targeting NS1 Protein Protects Immunocompetent Adult Mice in a Lethal Challenge Model

Brault, Aaron C.; Domi, Arban; McDonald, Erin; Talmi-Frank, Dalit; McCurley, Nathanael; Basu, Rahul; Robinson, Harriet L.; Hellerstein, Michael; Duggal, Nisha K.; Bowen, Richard A.; Guirakhoo, Farshad

doi:10.1038/s41598-017-15039-8

Cited by 108 publications

(101 citation statements)

References 40 publications

(38 reference statements)

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“…These studies highlight the value of including the NS1 protein in candidate vaccines for flaviviruses. During revision of our manuscript, Brault et al reported that intramuscular immunization of immunocompetent mice with the Modified Vaccinia Ankara (MVA) vector expressing NS1 (MVA-ZIKV-NS1) vaccine candidate provided 100% protection against a lethal intracerebral dose of ZIKV (strain MR766) 61 . However, their study did not evaluate the efficacy of MVA-ZIKV-NS1 in A129 mice which is more highly sensitive to ZIKV infection.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

confidence: 99%

A Zika virus vaccine expressing premembrane-envelope-NS1 polyprotein

et al. 2018

Nat Commun

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“…Finally, MVA and MV vectors have been engineered to express the NS1 or prM-ENV proteins of ZIKV, respectively. Protection in pre-clinical models with these candidates has also been reported 73 .…”

Section: Protection In Pre-clinical Modelsmentioning

confidence: 89%

Zika virus vaccines

2018

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The recent epidemic of Zika virus (ZIKV) in the Americas has revealed the devastating consequences of ZIKV infection, particularly in pregnant women. Congenital Zika syndrome, characterized by malformations and microcephaly in neonates as well as developmental challenges in children, highlights the need for the development of a safe and effective vaccine. Multiple vaccine candidates have been developed and have shown promising results in both animal models and phase I clinical trials. However, important challenges remain for clinical development of these vaccines. In this Progress, we discuss recent preclinical studies and lessons learned from first in-human clinical trials with ZIKV vaccines.

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“…Furthermore, Pérez et al constructed an MVA-ZIKV vaccine expressing the prME gene, which is capable of expressing Virus-Like Particles (VLPs) and inducing partial protection in mice after a ZIKV challenge, upon a homologous prime-boost approach [21]. Of particular interest, an MVA vaccine expressing the non-structural protein 1 (NS1) of ZIKV has been demonstrated to be 100% effective in both a single-or two-dose vaccination [22]. Here, we developed four MVA-ZIKV vaccines expressing the envelope gene, with or without its transmembrane domain, both in the presence and absence of the prM antigens.…”

Section: Discussionmentioning

confidence: 99%

Assessment of Immunogenicity and Efficacy of a Zika Vaccine Using Modified Vaccinia Ankara Virus as Carriers

et al. 2019

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Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that has spread to more than 70 countries worldwide since 2015. Despite active research, there are currently no licensed vaccines or therapeutics. We have previously reported the development of various adenoviral vectored vaccine candidates (ChAdOx1 ZIKV) with the ability to stimulate effective immunity in mice and provide protection upon a ZIKV challenge model, using a non-adjuvanted single vaccination approach. In this study, we constructed various modified vaccinia Ankara (MVA) viruses to express the ZIKV Envelope (E) with modifications on the precursor membrane (prM) or on the C-terminus envelope transmembrane domain (TM), similar to our ChAdOx1 vaccine candidates. MVA-ZIKV vaccine candidates were evaluated as a non-adjuvanted single vaccination regimen against a ZIKV Brazilian isolate, using viraemia as the correlate of protection. Here, we report the induction of a modest level of anti-ZIKV E antibodies by all MVA vectored vaccines and sub-optimal efficacy in a ZIKV challenge model. Our results indicate the requirement of additional strategies when using MVA-ZIKV vaccines to afford sterile protection upon a non-adjuvanted and single vaccination regime.

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A Zika Vaccine Targeting NS1 Protein Protects Immunocompetent Adult Mice in a Lethal Challenge Model

Cited by 108 publications

References 40 publications

A Zika virus vaccine expressing premembrane-envelope-NS1 polyprotein

A Zika virus vaccine expressing premembrane-envelope-NS1 polyprotein

Zika virus vaccines

Assessment of Immunogenicity and Efficacy of a Zika Vaccine Using Modified Vaccinia Ankara Virus as Carriers

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