Zika Virus Vaccines — A Full Field and Looking for the Closers

Thomas, Stephen J.

doi:10.1056/nejmcibr1701402

Cited by 14 publications

(11 citation statements)

References 8 publications

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“… 56 Therefore, DIII subunit vaccines are not among the leading candidates (and recently approved) for dengue vaccines, nor are they prominent among platforms leading the way for ZIKV vaccine design. 11 , 57 , 58 Our results indicate that antibodies targeting the cryptic C–C′ loop are inherently less protective against ZIKV infection in vitro and in vivo than previously described potent neutralizing antibodies targeting the upper lateral surface of DIII. Although the binding affinities were very high, the neutralizing activities were low.…”

Section: Discussionmentioning

confidence: 57%

“…Understanding the human antibody response to ZIKV is central to the development of effective vaccines and serodiagnostics. 9 , 10 , 11 , 12 Three-dimensional cryo-electron microscopy structures of ZIKV reveal that it shares a high structural similarity to other flaviviruses with known structures. 13 , 14 The ZIKV envelope (E) glycoprotein, which was found to be a dimer on the surface of a mature virion, mediates viral entry, membrane fusion, and serves as the major target for neutralizing antibodies.…”

Section: Introductionmentioning

confidence: 99%

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Neutralization of Zika virus by germline-like human monoclonal antibodies targeting cryptic epitopes on envelope domain III

et al. 2017

Emerging Microbes & Infections

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The Zika virus (ZIKV), a flavivirus transmitted by Aedes mosquitoes, has emerged as a global public health concern. Pre-existing cross-reactive antibodies against other flaviviruses could modulate immune responses to ZIKV infection by antibody-dependent enhancement, highlighting the importance of understanding the immunogenicity of the ZIKV envelope protein. In this study, we identified a panel of human monoclonal antibodies (mAbs) that target domain III (DIII) of the ZIKV envelope protein from a very large phage-display naive antibody library. These germline-like antibodies, sharing 98%–100% hoLogy with their corresponding germline IGHV genes, bound ZIKV DIII specifically with high affinities. One mAb, m301, broadly neutralized the currently circulating ZIKV strains and showed a synergistic effect with another mAb, m302, in neutralizing ZIKV in vitro and in a mouse model of ZIKV infection. Interestingly, epitope mapping and competitive binding studies suggest that m301 and m302 bind adjacent regions of the DIII C–C′ loop, which represents a recently identified cryptic epitope that is intermittently exposed in an uncharacterized virus conformation. This study extended our understanding of antigenic epitopes of ZIKV antibodies and has direct implications for the design of ZIKV vaccines.

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Section: Discussionmentioning

confidence: 57%

Section: Introductionmentioning

confidence: 99%

Neutralization of Zika virus by germline-like human monoclonal antibodies targeting cryptic epitopes on envelope domain III

et al. 2017

Emerging Microbes & Infections

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“…Recently, a theoretical concern of enhancement of ZIKV infection or pathology by pre-existing antibodies against other flaviviruses was raised based on experiments in vitro and in small animals. There is no evidence of such enhancement occurring in humans and the available NHP data argue otherwise 46,47 . Nevertheless it may be necessary to demonstrate clinically that there is no enhancement of CYZ vaccine infection by cross-reactive anti-flavivirus antibodies and thus, that vaccine safety would not be compromised in pre-immune subjects.…”

Section: Discussionmentioning

confidence: 99%

Chimeric yellow fever 17D-Zika virus (ChimeriVax-Zika) as a live-attenuated Zika virus vaccine

Giel–Moloney

Goncalvez

Catalan

et al. 2018

Sci Rep

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Zika virus (ZIKV) is an emerging mosquito-borne pathogen representing a global health concern. It has been linked to fetal microcephaly and other birth defects and neurological disorders in adults. Sanofi Pasteur has engaged in the development of an inactivated ZIKV vaccine, as well as a live chimeric vaccine candidate ChimeriVax-Zika (CYZ) that could become a preferred vaccine depending on future ZIKV epidemiology. This report focuses on the CYZ candidate that was constructed by replacing the pre-membrane and envelope (prM-E) genes in the genome of live attenuated yellow fever 17D vaccine virus (YF 17D) with those from ZIKV yielding a viable CYZ chimeric virus. The replication rate of CYZ in the Vero cell substrate was increased by using a hybrid YF 17D-ZIKV signal sequence for the prM protein. CYZ was highly attenuated both in mice and in human in vitro models (human neuroblastoma and neuronal progenitor cells), without the need for additional attenuating modifications. It exhibited significantly reduced viral loads in organs compared to a wild-type ZIKV and a complete lack of neuroinvasion following inoculation of immunodeficient A129 mice. A single dose of CYZ elicited high titers of ZIKV-specific neutralizing antibodies in both immunocompetent and A129 mice and protected animals from ZIKV challenge. The data indicate that CYZ is a promising vaccine candidate against ZIKV.

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“…Dedicated efforts to develop a safe and effective vaccine against Zika virus are in full swing. 100,101 Given the fundamental sexbased differences in the innate and adaptive immune responses, failure to consider immunologic differences between women and men in the design of a Zika virus vaccine could undermine its effectiveness and successful implementation. 102 In general, women have a more robust antiviral immune and inflammatory response compared with men.…”

Section: Implications Of Sex-based Immunologic Differences For Zika Vmentioning

confidence: 99%

Sex Matters in Neuroinfectious Diseases

Chow

2017

Semin Neurol

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Although sex and gender have a major impact on the susceptibility and immunologic response to infectious diseases, these factors are often neglected. Identifying the mechanisms underlying sex-based differences in infectious diseases will facilitate the rational design and implementation of preventive and therapeutic strategies that reduce risk and improve outcomes for women and men. In this article, we discuss two examples in neuroinfectious diseases of how sex matters: (1) the heightened risk of cerebrovascular disease in women living with HIV infection and (2) the implications of Zika virus infection on sexual and reproductive health and vaccine development for women.

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Zika Virus Vaccines — A Full Field and Looking for the Closers

Cited by 14 publications

References 8 publications

Neutralization of Zika virus by germline-like human monoclonal antibodies targeting cryptic epitopes on envelope domain III

Neutralization of Zika virus by germline-like human monoclonal antibodies targeting cryptic epitopes on envelope domain III

Chimeric yellow fever 17D-Zika virus (ChimeriVax-Zika) as a live-attenuated Zika virus vaccine

Sex Matters in Neuroinfectious Diseases

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