A single-dose live attenuated chimeric vaccine candidate against Zika virus

Chin, Wei-Xin; Lee, Regina Ching Hua; Kaur, Parvinder; Lew, Tian Sheng; Yogarajah, Thinesshwary; Kong, Hao Yuin; Teo, Zi-Yun; Salim, Cyrill Kafi; Zhang, Rongrong; Li, Xiaofeng; Alonso, Sylvie; Qin, Cheng‐Feng; Chu, Justin Jang Hann

doi:10.1038/s41541-021-00282-y

Cited by 13 publications

(18 citation statements)

References 52 publications

(153 reference statements)

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“…A chimeric ZIKV LAV based on a similar DENV-2 PDK-53 backbone (VacDZ) was recently described 36 . Differences between our D2/ZK-V candidates and VacDZ include the number of DENV-2 PDK-53 specific mutations, the C-terminal chimeric junction, and the inclusion of Vero-adaptive substitutions.…”

Section: Discussionmentioning

confidence: 99%

Single dose of chimeric dengue-2/Zika vaccine candidate protects mice and non-human primates against Zika virus

et al. 2021

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The development of a safe and effective Zika virus (ZIKV) vaccine has become a global health priority since the widespread epidemic in 2015-2016. Based on previous experience in using the well-characterized and clinically proven dengue virus serotype-2 (DENV-2) PDK-53 vaccine backbone for live-attenuated chimeric flavivirus vaccine development, we developed chimeric DENV-2/ZIKV vaccine candidates optimized for growth and genetic stability in Vero cells. These vaccine candidates retain all previously characterized attenuation phenotypes of the PDK-53 vaccine virus, including attenuation of neurovirulence for 1-day-old CD-1 mice, absence of virulence in interferon receptor-deficient mice, and lack of transmissibility in the main mosquito vectors. A single DENV-2/ZIKV dose provides protection against ZIKV challenge in mice and rhesus macaques. Overall, these data indicate that the ZIKV live-attenuated vaccine candidates are safe, immunogenic and effective at preventing ZIKV infection in multiple animal models, warranting continued development.

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Section: Discussionmentioning

confidence: 99%

Single dose of chimeric dengue-2/Zika vaccine candidate protects mice and non-human primates against Zika virus

et al. 2021

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“…Subsequently, the chimeric vaccines retain the highly attenuated phenotype of backbone viruses. The chimera vaccines also maintain a low-risk risk of reversion to virulent wild-type strains compared to the engineering attenuated mutations in LAVs [ 54 , 55 ]. Despite potential concerns of cross-reactive immunity against backbone virus, the chimera vaccines often provide dual protection against both target and backbone viruses challenge due to the induction of T and B cell responses against both [ 56 , 57 ].…”

Section: Zikv Lavsmentioning

confidence: 99%

“…Lastly, VacDZ was developed using the clinically validated DENV serotype-2 (DENV-2) derivative, PDK-53, as the backbone. The candidate chimeric vaccine induces neutralizing antibodies and a strong T helper 1 response in AG129 mice and protects mice from lethal wild-type ZIKV infection [ 54 ].…”

Section: Zikv Lavsmentioning

confidence: 99%

Rational Development of Live-Attenuated Zika Virus Vaccines

Adam

Lee²

2023

Pathogens

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Zika virus (ZIKV), a re-emerging mosquito-borne flavivirus, has caused outbreaks in Africa, Asia, the Pacific, and, more recently, in the Americas. ZIKV has been associated with the neurological autoimmune disorder Guillain–Barre syndrome in adults and congenital Zika syndrome in fetuses and infants, including microcephaly, spontaneous abortion, and intrauterine growth restriction. It is considered to be a major threat to global public health due to its unprecedented clinical impact on humans. Currently, there are no specific prophylactics or therapeutics available to prevent or treat ZIKV infection. The development of a safe and efficacious ZIKV vaccine remains a global health priority. Since the recent outbreak, multiple platforms have been used in the development of candidate ZIKV vaccines. The candidate vaccines have been shown to elicit strong T cell and neutralization antibody responses and protect against ZIKV infection in animal models. Some candidates have progressed successfully to clinical trials. Live-attenuated vaccines, which induce rapid and durable protective immunity, are one of the most important strategies for controlling flavivirus diseases. In this review, we discuss recent progress in the development of candidate live-attenuated ZIKV vaccines.

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“…Chimeric vaccines using the YFV 17D genome as a backbone have been developed and tested for efficacy and lack of neurovirulence as well, replacing the envelope and pre-membrane proteins with target viruses. Some examples include vaccines against West Nile virus, Japanese encephalitis virus, Zika virus, and dengue viruses have been tested for neurovirulence and shown significant attenuation [25][26][27][28][29][30].…”

Section: Attenuation Of Neurovirulence In Live Viral Vaccinesmentioning

confidence: 99%

Live Viral Vaccine Neurovirulence Screening: Current and Future Models

Fulton¹,

Bailey²

2021

Vaccines

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Live viral vaccines are one of the most successful methods for controlling viral infections but require strong evidence to indicate that they are properly attenuated. Screening for residual neurovirulence is an important aspect for live viral vaccines against potentially neurovirulent diseases. Approximately half of all emerging viral diseases have neurological effects, so testing of future vaccines will need to be rapid and accurate. The current method, the monkey neurovirulence test (MNVT), shows limited translatability for human diseases and does not account for different viral pathogenic mechanisms. This review discusses the MNVT and potential alternative models, including in vivo and in vitro methods. The advantages and disadvantages of these methods are discussed, and there are promising data indicating high levels of translatability. There is a need to investigate these models more thoroughly and to devise more accurate and rapid alternatives to the MNVT.

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A single-dose live attenuated chimeric vaccine candidate against Zika virus

Cited by 13 publications

References 52 publications

Single dose of chimeric dengue-2/Zika vaccine candidate protects mice and non-human primates against Zika virus

Single dose of chimeric dengue-2/Zika vaccine candidate protects mice and non-human primates against Zika virus

Rational Development of Live-Attenuated Zika Virus Vaccines

Live Viral Vaccine Neurovirulence Screening: Current and Future Models

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