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Vaccines
Special Issues
Vaccines against Flaviviruses and Alphaviruses: Recent Advances and Future Challenges
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Vaccines against Flaviviruses and Alphaviruses: Recent Advances and Future Challenges

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: 30 June 2024 | Viewed by 14107

Special Issue Editors

Dr. Young Chan Kim

E-Mail Website
Guest Editor
1. The Jenner Institute, ORCRB, Nuffield Department of Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7DQ, UK
2. Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
Interests: flavivirus vaccines; alphavirus-based vaccines; zika vaccines; dengue vaccines; chikungunya vaccines; VLP; recombinant viral vectors; chimpanzee adenovirus (ChAdOx); MVA
Special Issues, Collections and Topics in MDPI journals
Dr. Arturo Reyes-Sandoval

E-Mail Website
Guest Editor
1. The Jenner Institute, ORCRB, Nuffield Department of Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7DQ, UK
2. Instituto Politécnico Nacional, IPN. Av. Luis Enrique Erro s/n. Unidad Adolfo López Mateos, Mexico City, Mexico
Interests: plasmodium vivax; pre-erythrocytic malaria vaccines; flavivirus vaccines; alphavirus-based vaccines; zika vaccines; dengue vaccines; chikungunya vaccines; VLP; recombinant viral vectors; chimpanzee adenovirus (ChAdOx); MVA
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The mosquito-borne viruses such as Dengue (DENV), Zika (ZIKV) and Chikungunya (CHIKV) viruses have emerged in recent decades affecting millions of people worldwide. These flaviviruses and alphaviruses can be classified into a broader category of arboviruses, and they cause significant disease burdens and public health concerns. Vaccine development against arboviruses has experienced swift progress after the sudden (re)emergence of cases of DENV, CHIKV and ZIKV in the last two decades. Despite the fact that there are no licensed vaccines against ZIKV and CHIKV, the wide range of vaccine platforms including both classic and new approaches such as inactivated and attenuated, proteins, virus-like particles (VLPs), viral vectors, DNA and mRNA are currently being tested in pre-clinical studies and in clinical trials which could lead to the future licensing of vaccines.

This Special Issue will feature vaccines against flaviviruses and alphaviruses of medical importance in humans with a particular focus on the design, development and validation of new vaccine candidates and the animal model. We welcome the submission of all types of articles, including short reports, original research, and reviews for this issue. We look forward to receiving your contributions.

Dr. Young Chan Kim
Dr. Arturo Reyes-Sandoval
Guest Editors

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

  • vaccine
  • arbovirus
  • flavivirus
  • alphavirus
  • Zika virus
  • dengue virus
  • chikungunya virus
  • pre-clinical development
  • clinical trials

Published Papers (7 papers)

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Editorial

Jump to: Research, Review

4 pages, 4069 KiB  
Editorial
Recent Developments in Vaccines against Flaviviruses and Alphaviruses
by Young Chan Kim and Arturo Reyes-Sandoval
Vaccines 2023, 11(2), 448; https://doi.org/10.3390/vaccines11020448 - 15 Feb 2023
Cited by 2 | Viewed by 1395
Abstract
In the twenty-first century, newly emerging viruses which are mostly zoonotic or vector-borne have continuously threatened public health and caused outbreaks of global concern [...] Full article
(This article belongs to the Special Issue Vaccines against Flaviviruses and Alphaviruses: Recent Advances and Future Challenges)
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Research

Jump to: Editorial, Review

14 pages, 2923 KiB  
Article
The Adjuvant Activity of BCG Cell Wall Cytoskeleton on a Dengue Virus-2 Subunit Vaccine
by Tuksin Jearanaiwitayakul, Saradee Warit, Kritsadayut Lekjinda, Mathurin Seesen, Jitra Limthongkul, Panuwat Midoeng, Panya Sunintaboon and Sukathida Ubol
Vaccines 2023, 11(8), 1344; https://doi.org/10.3390/vaccines11081344 - 09 Aug 2023
Viewed by 1483
Abstract
The uneven immunogenicity of the attenuated tetravalent dengue vaccine has made it difficult to achieve balanced protection against all four serotypes of the dengue virus (DENV). To overcome this problem, non-replicative vaccines have come into focus, as their immunogenicity is adjustable. This approach [...] Read more.
The uneven immunogenicity of the attenuated tetravalent dengue vaccine has made it difficult to achieve balanced protection against all four serotypes of the dengue virus (DENV). To overcome this problem, non-replicative vaccines have come into focus, as their immunogenicity is adjustable. This approach is excellent for multivalent vaccines but commonly faces the issue of low immunogenicity. In this present study, we developed a non-replicating dengue vaccine composed of UV-inactivated dengue virus-2 (UV-DENV-2) and DENV-2 NS1-279 protein encapsidated within nanoparticles. This vaccine candidate was administered in the presence of BCG cell wall cytoskeleton (BCG-CWS) as an adjuvant. We revealed, here, that encapsidated immunogens with BCG-CWS exerted potent activities on both B and T cells and elicited Th-1/Th-2 responses in mice. This was evidenced by BCG-CWS significantly augmenting antibody-mediated complement-fixing activity, strongly stimulating the antigen-specific polyfunctional T cell responses, and activating mixed Th-1/Th-2 responses specific to DENV-2- and NS1-279 antigens. In conclusion, BCG-CWS potently adjuvanted the inactivated DENV-2 and DENV subunit immunogens. The mechanism of adjuvanticity remains unclear. This study revealed the potential use of BCG-CWS in vaccine development. Full article
(This article belongs to the Special Issue Vaccines against Flaviviruses and Alphaviruses: Recent Advances and Future Challenges)
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16 pages, 1513 KiB  
Article
Recombinant Modified Vaccinia Virus Ankara Expressing a Glycosylation Mutant of Dengue Virus NS1 Induces Specific Antibody and T-Cell Responses in Mice
by Lucas Wilken, Sonja Stelz, Ayse Agac, Gerd Sutter, Chittappen Kandiyil Prajeeth and Guus F. Rimmelzwaan
Vaccines 2023, 11(4), 714; https://doi.org/10.3390/vaccines11040714 - 23 Mar 2023
Cited by 2 | Viewed by 1613
Abstract
The four serotypes of dengue virus (DENV1–4) continue to pose a major public health threat. The first licenced dengue vaccine, which expresses the surface proteins of DENV1–4, has performed poorly in immunologically naïve individuals, sensitising them to antibody-enhanced dengue disease. DENV non-structural protein [...] Read more.
The four serotypes of dengue virus (DENV1–4) continue to pose a major public health threat. The first licenced dengue vaccine, which expresses the surface proteins of DENV1–4, has performed poorly in immunologically naïve individuals, sensitising them to antibody-enhanced dengue disease. DENV non-structural protein 1 (NS1) can directly induce vascular leakage, the hallmark of severe dengue disease, which is blocked by NS1-specific antibodies, making it an attractive target for vaccine development. However, the intrinsic ability of NS1 to trigger vascular leakage is a potential drawback of its use as a vaccine antigen. Here, we modified DENV2 NS1 by mutating an N-linked glycosylation site associated with NS1-induced endothelial hyperpermeability and used modified vaccinia virus Ankara (MVA) as a vector for its delivery. The resulting construct, rMVA-D2-NS1-N207Q, displayed high genetic stability and drove efficient secretion of NS1-N207Q from infected cells. Secreted NS1-N207Q was composed of dimers and lacked N-linked glycosylation at position 207. Prime–boost immunisation of C57BL/6J mice induced high levels of NS1-specific antibodies binding various conformations of NS1 and elicited NS1-specific CD4+ T-cell responses. Our findings support rMVA-D2-NS1-N207Q as a promising and potentially safer alternative to existing NS1-based vaccine candidates, warranting further pre-clinical testing in a relevant mouse model of DENV infection. Full article
(This article belongs to the Special Issue Vaccines against Flaviviruses and Alphaviruses: Recent Advances and Future Challenges)
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20 pages, 1915 KiB  
Article
Characterization of Live-Attenuated Powassan Virus Vaccine Candidates Identifies an Efficacious Prime-Boost Strategy for Mitigating Powassan Virus Disease in a Murine Model
by Andrew M. Cheung, Elaine Z. Yip, Alison W. Ashbrook, Niluka Goonawardane, Corrine Quirk, Charles M. Rice, Margaret R. MacDonald and Hans-Heinrich Hoffmann
Vaccines 2023, 11(3), 612; https://doi.org/10.3390/vaccines11030612 - 08 Mar 2023
Cited by 3 | Viewed by 1953
Abstract
Powassan virus (POWV) is an emerging tick-borne virus and cause of lethal encephalitis in humans. The lack of treatment or prevention strategies for POWV disease underscores the need for an effective POWV vaccine. Here, we took two independent approaches to develop vaccine candidates. [...] Read more.
Powassan virus (POWV) is an emerging tick-borne virus and cause of lethal encephalitis in humans. The lack of treatment or prevention strategies for POWV disease underscores the need for an effective POWV vaccine. Here, we took two independent approaches to develop vaccine candidates. First, we recoded the POWV genome to increase the dinucleotide frequencies of CpG and UpA to potentially attenuate the virus by raising its susceptibility to host innate immune factors, such as the zinc-finger antiviral protein (ZAP). Secondly, we took advantage of the live-attenuated yellow fever virus vaccine 17D strain (YFV-17D) as a vector to express the structural genes pre-membrane (prM) and envelope (E) of POWV. The chimeric YFV-17D-POWV vaccine candidate was further attenuated for in vivo application by removing an N-linked glycosylation site within the nonstructural protein (NS)1 of YFV-17D. This live-attenuated chimeric vaccine candidate significantly protected mice from POWV disease, conferring a 70% survival rate after lethal challenge when administered in a homologous two-dose regimen. Importantly, when given in a heterologous prime-boost vaccination scheme, in which vaccination with the initial chimeric virus was followed by a protein boost with the envelope protein domain III (EDIII), 100% of the mice were protected without showing any signs of morbidity. Combinations of this live-attenuated chimeric YFV-17D-POWV vaccine candidate with an EDIII protein boost warrant further studies for the development of an effective vaccine strategy for the prevention of POWV disease. Full article
(This article belongs to the Special Issue Vaccines against Flaviviruses and Alphaviruses: Recent Advances and Future Challenges)
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19 pages, 2488 KiB  
Article
Generation of a Live-Attenuated Strain of Chikungunya Virus from an Indian Isolate for Vaccine Development
by Sreeja R. Nair, Rachy Abraham and Easwaran Sreekumar
Vaccines 2022, 10(11), 1939; https://doi.org/10.3390/vaccines10111939 - 16 Nov 2022
Cited by 2 | Viewed by 2353
Abstract
Chikungunya virus (CHIKV) re-emergence in the last decade has resulted in explosive epidemics. Along with the classical symptoms of fever and debilitating arthralgia, there were occurrences of unusual clinical presentations such as neurovirulence and mortality. These generated a renewed global interest to develop [...] Read more.
Chikungunya virus (CHIKV) re-emergence in the last decade has resulted in explosive epidemics. Along with the classical symptoms of fever and debilitating arthralgia, there were occurrences of unusual clinical presentations such as neurovirulence and mortality. These generated a renewed global interest to develop prophylactic vaccines. Here, using the classical approach of virus attenuation, we developed an attenuated CHIKV strain (RGCB355/KL08-p75) for the purpose. Repeated passaging (75 times) of a local clinical isolate of ECSA lineage virus in U-87 MG human astrocytoma cells, an interferon-response-deficient cell line, resulted in efficient adaptation and attenuation. While experimental infection of 3-day old CHIKV-susceptible BALB/c pups with the parent strain RGCB355/KL08-p4 resulted in death of all the animals, there was 100% survival in mice infected with the attenuated p75. In adult, immunocompetent, CHIKV-non-susceptible C57BL/6 mice, inoculation with p75 induced high antibody response without any signs of disease. Both p4 and p75 strains are uniformly lethal to interferon-response-deficient AG129 mice. Passive protection studies in AG129 mice using immune serum against p75 resulted in complete survival. Whole-genome sequencing identified novel mutations that might be responsible for virus attenuation. Our results establish the usefulness of RGCB355/KL08-p75 as a strain for vaccine development against chikungunya. Full article
(This article belongs to the Special Issue Vaccines against Flaviviruses and Alphaviruses: Recent Advances and Future Challenges)
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17 pages, 14270 KiB  
Article
Designing an Epitope-Based Peptide Vaccine Derived from RNA-Dependent RNA Polymerase (RdRp) against Dengue Virus Serotype 2
by Irma F. Wahongan, Elly J. Suoth, Fatimawali, Saad Alhumaid, Hawra Albayat, Mohammed Aljeldah, Basim R. Al Shammari, Mutaib M. Mashraqi, Ahmad A. Alshehri, Tarek Sulaiman, Safaa A. Turkistani, Ameen S. S. Alwashmi, Mohammed Garout, Trina Ekawati Tallei and Ali A. Rabaan
Vaccines 2022, 10(10), 1734; https://doi.org/10.3390/vaccines10101734 - 17 Oct 2022
Cited by 2 | Viewed by 1764
Abstract
Dengue fever (DF) continues to be one of the tropical and subtropical health concerns. Its prevalence tends to increase in some places in these regions. This disease is caused by the dengue virus (DENV), which is transmitted through the mosquitoes Aedes aegypti and [...] Read more.
Dengue fever (DF) continues to be one of the tropical and subtropical health concerns. Its prevalence tends to increase in some places in these regions. This disease is caused by the dengue virus (DENV), which is transmitted through the mosquitoes Aedes aegypti and A. albopictus. The treatment of DF to date is only supportive and there is no definitive vaccine to prevent this disease. The non-structural DENV protein, RNA-dependent RNA Polymerase (RdRp), is involved in viral replication. The RdRp-derived peptides can be used in the construction of a universal dengue vaccine. These peptides can be utilized as epitopes to induce immunity. This study was an in silico evaluation of the affinity of the potential epitope for the universal dengue vaccine to dendritic cells and the bonds between the epitope and the dendritic cell receptor. The peptide sequence MGKREKKLGEFGKAKG generated from dengue virus subtype 2 (DENV-2) RdRp was antigenic, did not produce allergies, was non-toxic, and had no homology with the human genome. The potential epitope-based vaccine MGKREKKLGEFGKAKG binds stably to dendritic cell receptors with a binding free energy of −474,4 kcal/mol. This epitope is anticipated to induce an immunological response and has the potential to serve as a universal dengue virus vaccine candidate. Full article
(This article belongs to the Special Issue Vaccines against Flaviviruses and Alphaviruses: Recent Advances and Future Challenges)
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Review

Jump to: Editorial, Research

13 pages, 620 KiB  
Review
Chikungunya Virus: Priority Pathogen or Passing Trend?
by Gerardo Montalvo Zurbia-Flores, Arturo Reyes-Sandoval and Young Chan Kim
Vaccines 2023, 11(3), 568; https://doi.org/10.3390/vaccines11030568 - 01 Mar 2023
Cited by 4 | Viewed by 2602
Abstract
Chikungunya virus (CHIKV) is considered a priority pathogen and a major threat to global health. While CHIKV infections may be asymptomatic, symptomatic patients can develop chikungunya fever (CHIKF) characterized by severe arthralgia which often transitions into incapacitating arthritis that could last for years [...] Read more.
Chikungunya virus (CHIKV) is considered a priority pathogen and a major threat to global health. While CHIKV infections may be asymptomatic, symptomatic patients can develop chikungunya fever (CHIKF) characterized by severe arthralgia which often transitions into incapacitating arthritis that could last for years and lead to significant loss in health-related quality of life. Yet, Chikungunya fever (CHIKF) remains a neglected tropical disease due to its complex epidemiology and the misrepresentation of its incidence and disease burden worldwide. Transmitted to humans by infected Aedes mosquitoes, CHIKV has dramatically expanded its geographic distribution to over 100 countries, causing large-scale outbreaks around the world and putting more than half of the population of the world at risk of infection. More than 50 years have passed since the first CHIKV vaccine was reported to be in development. Despite this, there is no licensed vaccine or antiviral treatments against CHIKV to date. In this review, we highlight the clinical relevance of developing chikungunya vaccines by discussing the poor understanding of long-term disease burden in CHIKV endemic countries, the complexity of CHIKV epidemiological surveillance, and emphasising the impact of the global emergence of CHIKV infections. Additionally, our review focuses on the recent progress of chikungunya vaccines in development, providing insight into the most advanced vaccine candidates in the pipeline and the potential implications of their roll-out. Full article
(This article belongs to the Special Issue Vaccines against Flaviviruses and Alphaviruses: Recent Advances and Future Challenges)
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