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Vaccines
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Update on Flavivirus Vaccines
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Update on Flavivirus Vaccines

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Vaccines against (re)emerging and Tropical Infections Diseases".

Deadline for manuscript submissions: closed (30 April 2020) | Viewed by 30101

Special Issue Editor

Dr. Sarah George

E-Mail Website
Guest Editor
Department of Internal Medicine, Saint Louis University, 1100 S. Grand Blvd, St Louis, MO 63104, USA
Interests: Vaccine clinical trials; Flavivirus vaccine development; virology; immunity; HIV/HPgV interactions and virology

Special Issue Information

Dear Colleagues,

Flaviviruses are single-stranded RNA viruses of high pathogenicity and epidemic potential: Zika virus has spread globally in the past decade, and both yellow fever and dengue have had significant global outbreaks. While licensed vaccines exist with regard to multiple flaviviruses (YFV, JE, TBE, etc.), vaccine development has been hindered by unexpected safety issues post licensing, as with the Sanofi Dengvaxia. Multiple vaccine candidates for Zika, dengue, YF, and others are in human trials, and significant recent insights have been gained in flavivirus immunology and off-target vaccine effects.

Dr. Sarah George
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Vaccines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • flavivirus
  • vaccines
  • vaccine development
  • clinical trials

Published Papers (6 papers)

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Research

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14 pages, 2154 KiB  
Article
Protective Efficacy of a Chimeric Insect-Specific Flavivirus Vaccine against West Nile Virus
by Laura J. Vet, Yin Xiang Setoh, Alberto A. Amarilla, Gervais Habarugira, Willy W. Suen, Natalee D. Newton, Jessica J. Harrison, Jody Hobson-Peters, Roy A. Hall and Helle Bielefeldt-Ohmann
Vaccines 2020, 8(2), 258; https://doi.org/10.3390/vaccines8020258 - 29 May 2020
Cited by 20 | Viewed by 4361
Abstract
Virulent strains of West Nile virus (WNV) are highly neuro-invasive and human infection is potentially lethal. However, no vaccine is currently available for human use. Here, we report the immunogenicity and protective efficacy of a vaccine derived from a chimeric virus, which was [...] Read more.
Virulent strains of West Nile virus (WNV) are highly neuro-invasive and human infection is potentially lethal. However, no vaccine is currently available for human use. Here, we report the immunogenicity and protective efficacy of a vaccine derived from a chimeric virus, which was constructed using the structural proteins (prM and E) of the Kunjin strain of WNV (WNVKUN) and the genome backbone of the insect-specific flavivirus Binjari virus (BinJV). This chimeric virus (BinJ/WNVKUN-prME) exhibits an insect-specific phenotype and does not replicate in vertebrate cells. Importantly, it authentically presents the prM-E proteins of WNVKUN, which is antigenically very similar to other WNV strains and lineages. Therefore BinJ/WNVKUN-prME represents an excellent candidate to assess as a vaccine against virulent WNV strains, including the highly pathogenic WNVNY99. When CD1 mice were immunized with purified BinJ/WNVKUN-prME, they developed robust neutralizing antibody responses after a single unadjuvanted dose of 1 to 5 μg. We further demonstrated complete protection against viremia and mortality after lethal challenge with WNVNY99, with no clinical or subclinical pathology observed in vaccinated animals. These data suggest that BinJ/WNVKUN-prME represents a safe and effective WNV vaccine candidate that warrants further investigation for use in humans or in veterinary applications. Full article
(This article belongs to the Special Issue Update on Flavivirus Vaccines)
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14 pages, 1173 KiB  
Article
When Can One Vaccinate with a Live Vaccine after Wild-Type Dengue Infection?
by Bruno Guy, Eng Eong Ooi, Jose Ramos-Castañeda and Stephen J. Thomas
Vaccines 2020, 8(2), 174; https://doi.org/10.3390/vaccines8020174 - 9 Apr 2020
Cited by 4 | Viewed by 6322
Abstract
Recommendations have been issued for vaccinating with the Sanofi Pasteur tetravalent dengue vaccine (CYD-TDV, Dengvaxia®) individuals aged from 9 to 45/60 years old with a prior dengue virus (DENV) infection and living in endemic countries/areas. One question linked to these recommendations [...] Read more.
Recommendations have been issued for vaccinating with the Sanofi Pasteur tetravalent dengue vaccine (CYD-TDV, Dengvaxia®) individuals aged from 9 to 45/60 years old with a prior dengue virus (DENV) infection and living in endemic countries/areas. One question linked to these recommendations is to determine when it is possible to start vaccination after laboratory confirmed wild-type DENV infection, and this question can be relevant to any live vaccine to be used in endemic areas. To address it, we reviewed and discussed the immunological and practical considerations of live vaccination in this context. Firstly, the nature and kinetics of immune responses triggered by primary or secondary DENV infection may positively or negatively impact subsequent live vaccine take and associated clinical benefit, depending on when vaccination is performed after infection. Secondly, regarding practical aspects, the “easiest” situation would correspond to a confirmed acute dengue fever, only requiring knowing when the patient should come back for vaccination. However, in most cases, it will not be possible to firmly establish the actual date of infection and vaccination may have to take place during well-defined periods, regardless of when prior infection occurred. Evidence that informs health authorities and medical practitioners in formulating vaccine policies and implementing vaccine programs is thus needed. The present work reviewed the different elements of the guidance and proposes some key conclusions and recommendations. Full article
(This article belongs to the Special Issue Update on Flavivirus Vaccines)
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16 pages, 1718 KiB  
Article
Effects of Adjuvants on the Immunogenicity and Efficacy of a Zika Virus Envelope Domain III Subunit Vaccine
by Xinyi Wang, Wanbo Tai, Xiaolu Zhang, Yusen Zhou, Lanying Du and Chuanlai Shen
Vaccines 2019, 7(4), 161; https://doi.org/10.3390/vaccines7040161 - 27 Oct 2019
Cited by 17 | Viewed by 4251
Abstract
Zika virus (ZIKV), a mosquito-borne flavivirus, has attracted global attention due to its close association with congenital Zika syndrome and neurological diseases, and transmission through additional routes, such as sexual contact. Currently there are no vaccines approved for ZIKV, and thus, there is [...] Read more.
Zika virus (ZIKV), a mosquito-borne flavivirus, has attracted global attention due to its close association with congenital Zika syndrome and neurological diseases, and transmission through additional routes, such as sexual contact. Currently there are no vaccines approved for ZIKV, and thus, there is an urgent need to develop an effective and safe ZIKV vaccine. Domain III (DIII) of the ZIKV envelope (E) protein is an important vaccine target, and a vaccine developed using a mutant DIII of E (EDIII) protein protects adult and pregnant mice, and unborn offspring, against ZIKV infection. Here, we have used immunocompetent BALB/c mice treated with anti-interferon-α/β receptor 1 (Ifnar1) antibodies to investigate whether three adjuvants (aluminum (Alum), monophosphoryl lipid A (MPL), and MF59), either alone or in combination, could improve the efficacy of this EDIII subunit vaccine. Our data show that, although vaccine formulated with a single adjuvant induced a specific antibody and cellular immune response, and reduced viral load in mice challenged with ZIKV, the combination of Alum and MPL adjuvants led to a more robust and balanced immune response, stronger neutralizing activity against three recent ZIKV human strains, and greater protection against a high-dose ZIKV challenge. Particularly, the combination of Alum with MPL significantly reduced viral titers and viral RNA copy numbers in sera and tissues, including the male reproductive organs. Overall, this study has identified the combination of Alum and MPL as the most effective adjuvant for ZIKV EDIII subunit vaccines, and it has important implications for subunit vaccines against other enveloped viruses, including non-ZIKV flaviviruses. Full article
(This article belongs to the Special Issue Update on Flavivirus Vaccines)
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Review

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19 pages, 728 KiB  
Review
Current Status of Zika Virus Vaccines: Successes and Challenges
by Aryamav Pattnaik, Bikash R. Sahoo and Asit K. Pattnaik
Vaccines 2020, 8(2), 266; https://doi.org/10.3390/vaccines8020266 - 31 May 2020
Cited by 79 | Viewed by 7372
Abstract
The recently emerged Zika virus (ZIKV) spread to the Americas, causing a spectrum of congenital diseases including microcephaly in newborn and Guillain-Barré syndrome (GBS) in adults. The unprecedented nature of the epidemic and serious diseases associated with the viral infections prompted the global [...] Read more.
The recently emerged Zika virus (ZIKV) spread to the Americas, causing a spectrum of congenital diseases including microcephaly in newborn and Guillain-Barré syndrome (GBS) in adults. The unprecedented nature of the epidemic and serious diseases associated with the viral infections prompted the global research community to understand the immunopathogenic mechanisms of the virus and rapidly develop safe and efficacious vaccines. This has led to a number of ZIKV vaccine candidates that have shown significant promise in human clinical trials. These candidates include nucleic acid vaccines, inactivated vaccines, viral-vectored vaccines, and attenuated vaccines. Additionally, a number of vaccine candidates have been shown to protect animals in preclinical studies. However, as the epidemic has waned in the last three years, further development of the most promising vaccine candidates faces challenges in clinical efficacy trials, which is needed before a vaccine is brought to licensure. It is important that a coalition of government funding agencies and private sector companies is established to move forward with a safe and effective vaccine ready for deployment when the next ZIKV epidemic occurs. Full article
(This article belongs to the Special Issue Update on Flavivirus Vaccines)
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13 pages, 262 KiB  
Review
Disease Resurgence, Production Capability Issues and Safety Concerns in the Context of an Aging Population: Is There a Need for a New Yellow Fever Vaccine?
by Kay M. Tomashek, Mark Challberg, Seema U. Nayak and Helen F. Schiltz
Vaccines 2019, 7(4), 179; https://doi.org/10.3390/vaccines7040179 - 8 Nov 2019
Cited by 11 | Viewed by 4491
Abstract
Yellow fever is a potentially fatal, mosquito-borne viral disease that appears to be experiencing a resurgence in endemic areas in Africa and South America and spreading to non-endemic areas despite an effective vaccine. This trend has increased the level of concern about the [...] Read more.
Yellow fever is a potentially fatal, mosquito-borne viral disease that appears to be experiencing a resurgence in endemic areas in Africa and South America and spreading to non-endemic areas despite an effective vaccine. This trend has increased the level of concern about the disease and the potential for importation to areas in Asia with ecological conditions that can sustain yellow fever virus transmission. In this article, we provide a broad overview of yellow fever burden of disease, natural history, treatment, vaccine, prevention and control initiatives, and vaccine and therapeutic agent development efforts. Full article
(This article belongs to the Special Issue Update on Flavivirus Vaccines)

Other

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6 pages, 718 KiB  
Case Report
Clinical Challenges in a 49-Year-Old Patient with Severe Tick-Borne Myeloradiculitis Despite Complete Active Vaccination
by Julia Feige, Tobias Moser, Larissa Hauer, Slaven Pikija and Johann Sellner
Vaccines 2020, 8(1), 93; https://doi.org/10.3390/vaccines8010093 - 20 Feb 2020
Cited by 3 | Viewed by 2800
Abstract
Vaccination is an effective means to prevent infectious diseases including tick-borne encephalitis (TBE), an emerging Flavivirus infection. There is, however, only limited knowledge about risk of vaccination failure, the disease course and the challenges for work-up and care. Of note, there is evidence [...] Read more.
Vaccination is an effective means to prevent infectious diseases including tick-borne encephalitis (TBE), an emerging Flavivirus infection. There is, however, only limited knowledge about risk of vaccination failure, the disease course and the challenges for work-up and care. Of note, there is evidence that patients with breakthrough disease experience a more severe disease course. We report the case of a previously healthy 49-year-old woman who developed severe myeloradiculitis caused by the TBE virus despite receiving a complete cycle of primary immunization and booster vaccinations within the recommended timeframe. The disease course was characterized by progressive tetraparesis, pain and bladder dysfunction and necessitated intensive care unit admission (ICU) and the escalation of pain management. This case raises awareness for the recognition of breakthrough disease in younger patients and reinforces the need to develop measures to identify patients with insufficient protection. Full article
(This article belongs to the Special Issue Update on Flavivirus Vaccines)
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