Enemy of My Enemy: A Novel Insect-Specific Flavivirus Offers a Promising Platform for a Zika Virus Vaccine

Porier, Danielle L.; Wilson, Sarah N.; Auguste, Dawn I.; Leber, Andrew; Coutermarsh-Ott, Sheryl; Allen, Irving C.; Caswell, Clayton C.; Budnick, James A.; Bassaganya‐Riera, Josep; Hontecillas, Raquel; Weger-Lucarelli, James; Weaver, Scott C.; Auguste, Albert J.

doi:10.3390/vaccines9101142

Cited by 14 publications

(27 citation statements)

References 47 publications

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“…ISFs are effective vaccine vectors for flaviviruses, with the potential of a human clinical trial. Vaccines against ZIKV, DENV, WNV, and JEV are developed using ISF vectors, such as Binjari and Aripo viruses 23,25 . Here, CYV-ZIKV also elicited robust humoral immune responses in IFNAR −/− mice via mosquito bites and lasted for at least 5 months, with no ADE against DENV observed in vitro, which needs to be further confirmed in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…ISFs are also a promising platform for flavivirus vaccine development. Chimeric Binjari virus or Aripo virus expressing the envelope proteins of ZIKV, dengue virus (DENV), or yellow fever virus (YFV) could not replicate in vertebrates, but trigger protective immune responses in vertebrates [23][24][25] . Using a similar strategy, a chimeric insect-specific alphavirus, Eilat virus, expressing the envelope proteins of chikungunya virus (CHIKV), elicited robust protective immunity in monkeys 26 .…”

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confidence: 99%

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Suppression of flavivirus transmission from animal hosts to mosquitoes with a mosquito-delivered vaccine

et al. 2022

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Zoonotic viruses circulate in the natural reservoir and sporadically spill over into human populations, resulting in endemics or pandemics. We previously found that the Chaoyang virus (CYV), an insect-specific flavivirus (ISF), is replication-defective in vertebrate cells. Here, we develope a proof-of-concept mosquito-delivered vaccine to control the Zika virus (ZIKV) within inaccessible wildlife hosts using CYV as the vector. The vaccine is constructed by replacing the pre-membrane and envelope (prME) proteins of CYV with those of ZIKV, assigned as CYV-ZIKV. CYV-ZIKV replicates efficiently in Aedes mosquitoes and disseminates to the saliva, with no venereal or transovarial transmission observed. To reduce the risk of CYV-ZIKV leaking into the environment, mosquitoes are X-ray irradiated to ensure 100% infertility, which does not affect the titer of CYV-ZIKV in the saliva. Immunization of mice via CYV-ZIKV-carrying mosquito bites elicites robust and persistent ZIKV-specific immune responses and confers complete protection against ZIKV challenge. Correspondingly, the immunized mice could no longer transmit the challenged ZIKV to naïve mosquitoes. Therefore, immunization with an ISF-vectored vaccine via mosquito bites is feasible to induce herd immunity in wildlife hosts of ZIKV. Our study provides a future avenue for developing a mosquito-delivered vaccine to eliminate zoonotic viruses in the sylvatic cycle.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Suppression of flavivirus transmission from animal hosts to mosquitoes with a mosquito-delivered vaccine

et al. 2022

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“…ARPV/ZIKV containing the precursor PrM/E genes of ZIKV in replacement of the ARPV homologs retains the vertebrate host-restriction of ARPV. A single dose of this candidate vaccine elicited strong neutralizing antibodies, ZIKV-specific CD4 + and CD8 + T cell responses and offered complete protection against ZIKV-induced diseases and in utero transmission in both wild-type immunocompetent and IFN deficient (AB6) mice [ 66 ].…”

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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“…The copyright holder for this preprint this version posted March 1, 2023. ; https://doi.org/10.1101/2023.03.01.530296 doi: bioRxiv preprint candidates for both alphaviruses and flaviviruses [9,[11][12][13][14][15][16]. These "pseudo-inactivated" recombinant vaccines are extremely safe due to the natural vertebrate host-restriction conferred to them by the insect-specific virus backbone, yet still retain significant immunogenicity.…”

Section: Introductionmentioning

confidence: 99%

Humoral and T-cell-mediated responses to a pre-clinical Zika vaccine candidate that utilizes a unique insect-specific flavivirus platform

Porier¹,

Adam

Kang

et al. 2023

Preprint

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Vaccination is critical for the control and prevention of viral outbreaks, yet conventional vaccine platforms may involve trade-offs between immunogenicity and safety. Insect-specific viruses have emerged as a novel vaccine platform to overcome this challenge. Detailed studies of humoral and T-cell responses induced by new insect-specific flavivirus (ISFV)-based vaccine platforms are needed to better understand correlates of protection and improve vaccine efficacy. Previously, we used a novel ISFV called Aripo virus (ARPV) to create a Zika virus (ZIKV) vaccine candidate (designated ARPV/ZIKV). ARPV/ZIKV demonstrated exceptional safety and single-dose efficacy, completely protecting mice from a lethal ZIKV challenge. Here, we explore the development of immune responses induced by ARPV/ZIKV immunization and evaluate its correlates of protection. Passive transfer of ARPV/ZIKV-induced immune sera to naïve mice prior to challenge emphasized the importance of neutralizing antibodies as a correlate of protection. Depletion of T-cells in vaccinated mice and adoptive transfer of ARPV/ZIKV-primed T-cells to naïve mice prior to challenge indicated that ARPV/ZIKV-induced CD4+and CD8+T-cell responses contribute to the observed protection but may not be essential for protection during ZIKV challenge. However, vaccination of Rag1 KO, Tcra KO, and muMt−mice demonstrated the critical role for ARPV/ZIKV-induced T-cells in developing protective immune responses following vaccination. Overall, both humoral and T-cell-mediated responses induced by ISFV-based vaccines are important for comprehensive immunity, and ISFV platforms continue to be a promising method for future vaccine development.

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Enemy of My Enemy: A Novel Insect-Specific Flavivirus Offers a Promising Platform for a Zika Virus Vaccine

Cited by 14 publications

References 47 publications

Suppression of flavivirus transmission from animal hosts to mosquitoes with a mosquito-delivered vaccine

Suppression of flavivirus transmission from animal hosts to mosquitoes with a mosquito-delivered vaccine

Rational Development of Live-Attenuated Zika Virus Vaccines

Humoral and T-cell-mediated responses to a pre-clinical Zika vaccine candidate that utilizes a unique insect-specific flavivirus platform

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