Zika Vaccine Development—Current Progress and Challenges for the Future

Zika virus is an emergent pathogen that gained significant importance during the epidemic in South and Central America as unusual and alarming complications of infection were recognized. Although initially considered a self-limited benign infection, a panoply of neurologic complications were recognized including a Guillain–Barré-like syndrome and in-utero fetal infection causing microcephaly, blindness, and other congenital neurologic complications. Numerous Zika virus vaccines were developed, with nine different vaccines representing five different platforms entered into clinical trials, one progressing to Phase II. Here we review the current landscape and challenges confronting Zika virus vaccine development.

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T Cell Immunity and Zika Virus Vaccine Development

Trends in Immunology ◽

10.1016/j.it.2017.05.004 ◽

2017 ◽

Vol 38 (8) ◽

pp. 594-605 ◽

Cited By ~ 20

Author(s):

Noemia S. Lima ◽

Morgane Rolland ◽

Kayvon Modjarrad ◽

Lydie Trautmann

Keyword(s):

T Cell ◽

Virus Vaccine ◽

Zika Virus ◽

Vaccine Development ◽

T Cell Immunity ◽

Cell Immunity

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Will Attention by Vaccine Developers to the Host’s Nuclear Hormone Levels and Immunocompetence Improve Vaccine Success?

Vaccines ◽

10.3390/vaccines7010026 ◽

2019 ◽

Vol 7 (1) ◽

pp. 26 ◽

Cited By ~ 7

Author(s):

Robert Sealy ◽

Bart Jones ◽

Sherri Surman ◽

Rhiannon Penkert ◽

Stephane Pelletier ◽

...

Keyword(s):

Clinical Trials ◽

Virus Vaccine ◽

Vaccine Development ◽

Regulatory Elements ◽

Immunoglobulin Gene ◽

Antibody Isotype ◽

Hormone Levels ◽

Estrogen Response ◽

Syncytial Virus ◽

Study Participants

Despite extraordinary advances in fields of immunology and infectious diseases, vaccine development remains a challenge. The development of a respiratory syncytial virus vaccine, for example, has spanned more than 50 years of research with studies of more than 100 vaccine candidates. Dozens of attractive vaccine products have entered clinical trials, but none have completed the path to licensing. Human immunodeficiency virus vaccine development has proven equally difficult, as there is no licensed product after more than 30 years of pre-clinical and clinical research. Here, we examine vaccine development with attention to the host. We discuss how nuclear hormones, including vitamins and sex hormones, can influence responses to vaccines. We show how nuclear hormones interact with regulatory elements of immunoglobulin gene loci and how the deletion of estrogen response elements from gene enhancers will alter patterns of antibody isotype expression. Based on these findings, and findings that nuclear hormone levels are often insufficient or deficient among individuals in both developed and developing countries, we suggest that failed vaccine studies may in some cases reflect weaknesses of the host rather than the product. We encourage analyses of nuclear hormone levels and immunocompetence among study participants in clinical trials to ensure the success of future vaccine programs.

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Preliminary aggregate safety and immunogenicity results from three trials of a purified inactivated Zika virus vaccine candidate: phase 1, randomised, double-blind, placebo-controlled clinical trials

The Lancet ◽

10.1016/s0140-6736(17)33106-9 ◽

2018 ◽

Vol 391 (10120) ◽

pp. 563-571 ◽

Cited By ~ 100

Author(s):

Kayvon Modjarrad ◽

Leyi Lin ◽

Sarah L George ◽

Kathryn E Stephenson ◽

Kenneth H Eckels ◽

...

Keyword(s):

Clinical Trials ◽

Virus Vaccine ◽

Zika Virus ◽

Vaccine Candidate ◽

Phase 1 ◽

Controlled Clinical Trials ◽

Double Blind ◽

Double Blind Placebo

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Recent Advances in Zika Virus Vaccine Development

International Journal of Vaccine Research ◽

10.15226/2473-2176/2/2/00121 ◽

2017 ◽

Vol 2 (2) ◽

pp. 1-5

Author(s):

Sidra Shafique

Keyword(s):

Virus Vaccine ◽

Zika Virus ◽

Vaccine Development ◽

Recent Advances

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Zika Virus Vaccine Development

The Journal of Infectious Diseases ◽

10.1093/infdis/jix464 ◽

2017 ◽

Vol 216 (suppl_10) ◽

pp. S957-S963 ◽

Cited By ~ 15

Author(s):

Kaitlyn M Morabito ◽

Barney S Graham

Keyword(s):

Virus Vaccine ◽

Zika Virus ◽

Vaccine Development

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A Full-Length Infectious cDNA Clone of Zika Virus from the 2015 Epidemic in Brazil as a Genetic Platform for Studies of Virus-Host Interactions and Vaccine Development

mBio ◽

10.1128/mbio.01114-16 ◽

2016 ◽

Vol 7 (4) ◽

Cited By ~ 83

Author(s):

Konstantin A. Tsetsarkin ◽

Heather Kenney ◽

Rubing Chen ◽

Guangping Liu ◽

Hasmik Manukyan ◽

...

Keyword(s):

Vero Cell ◽

Cell Lines ◽

Cdna Clone ◽

Zika Virus ◽

Reverse Genetics ◽

Vaccine Development ◽

Infectious Cdna Clone ◽

Guillain Barre Syndrome ◽

Perinatal Development ◽

Guillain Barré

ABSTRACTAn arthropod-borne virus, Zika virus (ZIKV), has recently emerged as a major human pathogen. Associated with complications during perinatal development and Guillain-Barré syndrome in adults, ZIKV raises new challenges for understanding the molecular determinants of flavivirus pathogenesis. This underscores the necessity for the development of a reverse genetic system based on an epidemic ZIKV strain. Here, we describe the generation and characterization in cell cultures of an infectious cDNA clone of ZIKV isolated from the 2015 epidemic in Brazil. The cDNA-derived ZIKV replicated efficiently in a variety of cell lines, including those of both neuronal and placental origin. We observed that the growth of cDNA-derived virus was attenuated compared to the growth of the parental isolate in most cell lines, which correlates with substantial differences in sequence heterogeneity between these viruses that were determined by deep-sequencing analysis. Our findings support the role of genetic diversity in maintaining the replicative fitness of viral populations under changing conditions. Moreover, these results indicate that caution should be exercised when interpreting the results of reverse-genetics experiments in attempts to accurately predict the biology of natural viruses. Finally, a Vero cell-adapted cDNA clone of ZIKV was generated that can be used as a convenient platform for studies aimed at the development of ZIKV vaccines and therapeutics.IMPORTANCEThe availability of genetic tools and laboratory models determines the progress in understanding mechanisms of virus emergence and pathogenesis. Recent large-scale outbreaks of Zika virus (ZIKV) that were linked to complications during perinatal development and Guillain-Barré syndrome in adults emphasize the urgency for the development of a reverse-genetics system based on an epidemic ZIKV strain. Here, we report a stable infectious cDNA clone for ZIKV isolated during the 2015 epidemic in Brazil, as well as a Vero cell-adapted version of it, which will be used for virus-host interaction studies and vaccine development.

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Vaccine development against SARS-CoV-2: from virology to vaccine clinical trials

Coronaviruses ◽

10.2174/2666796701999201026205553 ◽

2020 ◽

Vol 01 ◽

Author(s):

Kimia Kardani ◽

Azam Bolhassani

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Phase Ii ◽

Immune Evasion ◽

Vaccine Development ◽

Vaccine Candidate ◽

Adenovirus Vector ◽

Vaccine Candidates ◽

Novel Coronavirus ◽

The Way

Abstract:: An urgent vaccine development is required against the recent pandemic of a novel coronavirus. Currently, there is no approved vaccine against COVID-19. Vaccination is proved to be the most beneficial way to protect human from infections. Up to now, several vaccine candidates have been conducted to different phases of clinical trials, and more vaccine candidates are on the way to enter the trials. Different vaccine types have developed including inactivated virus vaccines, subunit-based vaccines, adenovirus-vector vaccines, DNA-based vaccines, DC-based vaccines, and mRNA-based vaccines. The mRNA- 1273 was the first vaccine candidate that started evaluating in clinical trial. Also, AZD1222 is the first vaccine candidate that started phase II/III of clinical trials. Both of these vaccine candidates were considered as the promising vaccine candidates against SARS-CoV-2. This review aims to overview and share various strategies to develop efficient therapeutic and preventive vaccines based on the origin, biology, structure, and immune-evasion of SARS-CoV-2.

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