Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
7.3
3.8
Journals
Viruses
Special Issues
Flavivirus Vaccines
share announcement

Flavivirus Vaccines

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Viral Immunology, Vaccines, and Antivirals".

Deadline for manuscript submissions: closed (31 March 2021) | Viewed by 37314

Special Issue Editors

Dr. Ashley L. St. John

E-Mail Website
Guest Editor
The Laboratory of Immunity and Immune Pathology, Duke-NUS Medical School, Singapore 169857, Singapore
Interests: viral immunology; vaccines
Special Issues, Collections and Topics in MDPI journals
Dr. Abhay P.S. Rathore

E-Mail Website
Guest Editor
Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA

Special Issue Information

Dear Colleagues,

Flaviviruses consist of diverse group of pathogens responsible for hundreds of millions of human infections annually. While there are highly effective vaccines to certain flaviviruses, such as Yellow Fever Virus, other Flavivirus vaccines are largely in developmental stages. Many factors may govern natural infection clearance or vaccine effectiveness, including but not limited to the initiation of immune responses at the site of infection, the time between exposures to vaccines or natural infections, and the vaccine composition. Due to their close antigenic relationships, flaviviruses evoke immune responses that are cross-reactive, and this presents complex challenges for vaccine development. These cross-reactive immune responses could potentially be pathogenic or may provide Flavivirus cross-protection. In this Special Issue, we will highlight advances in Flavivirus vaccine development and in the understanding of host immune responses that can inform vaccine design. We also welcome research that will broaden our understanding of Flavivirus cross-reactive immune responses.

Dr. Ashley L. St. John
Dr. Abhay P.S. Rathore
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. Viruses 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 2600 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

  • Mosquito borne flaviviruses including Dengue, Zika, West Nile, Kunjin, Usutu, Ntaya, Japanese encephalitis, Yellow fever, and more
  • Tick-borne flaviviruses including but not limited to Omsk hemorrhagic fever, Powassan, and Kyasanur forest disease
  • Vaccines and vaccine platforms
  • Adjuvants
  • Adaptive immunity and Immune memory (T and B cell responses)
  • Flavivirus cross-reactive immune responses
  • Skin immunity
  • Host–virus protein interactions that may influence vaccine effectiveness

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue polices can be found here.

Published Papers (11 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

22 pages, 3134 KiB  
Article
Combination of E- and NS1-Derived DNA Vaccines: The Immune Response and Protection Elicited in Mice against DENV2
by Paolla Beatriz A. Pinto, Tamiris A. C. Barros, Lauro M. Lima, Agatha R. Pacheco, Maysa L. Assis, Bernardo A. S. Pereira, Antônio J. S. Gonçalves, Adriana S. Azevedo, Ana Gisele C. Neves-Ferreira, Simone M. Costa and Ada M. B. Alves
Viruses 2022, 14(7), 1452; https://doi.org/10.3390/v14071452 - 30 Jun 2022
Cited by 2 | Viewed by 2403
Abstract
The occurrence of dengue disease has increased radically in recent decades. Previously, we constructed the pE1D2 and pcTPANS1 DNA vaccines encoding the DENV2 envelope (E) and non-structural 1 (NS1) proteins, respectively. To decrease the number of plasmids in a tetravalent candidate vaccine, we [...] Read more.
The occurrence of dengue disease has increased radically in recent decades. Previously, we constructed the pE1D2 and pcTPANS1 DNA vaccines encoding the DENV2 envelope (E) and non-structural 1 (NS1) proteins, respectively. To decrease the number of plasmids in a tetravalent candidate vaccine, we constructed a bicistronic plasmid, pNS1/E/D2, encoding these two proteins simultaneously. We evaluated the protective immunity induced in mice vaccinated with the pNS1/E/D2 candidate and compared to the responses elicited by immunization with the former vaccines isolated or in combination. We transfected BHK-21 cells with the different plasmids and detected recombinant proteins by immunofluorescence and mass spectrometry assays to confirm antigen expression. BALB/c mice were inoculated with the DNA vaccines followed by a lethal DENV2 challenge. ELISA, PRNT50, and IFN-gamma ELISPOT assays were performed for the investigation of the humoral and cellular responses. We observed the concomitant expression of NS1 and E proteins in pNS1/E/D2-transfected cells. All E-based vaccines induced anti-E and neutralizing antibodies. However, anti-NS1 antibodies were only observed after immunization with the pcTPANS1 administered alone or combined with pE1D2. In contrast, splenocytes from pNS1/E/D2- or pcTPANS1 + pE1D2-vaccinated animals responded to NS1- and E-derived synthetic peptides. All the DNA vaccines conferred protection against DENV2. Full article
(This article belongs to the Special Issue Flavivirus Vaccines)
►▼ Show Figures

Figure 1

16 pages, 1200 KiB  
Article
Implications of Dengue Virus Maturation on Vaccine Induced Humoral Immunity in Mice
by Connor A. P. Scott, Alberto A. Amarilla, Summa Bibby, Natalee D. Newton, Roy A. Hall, Jody Hobson-Peters, David A. Muller, Keith J. Chappell, Paul R. Young, Naphak Modhiran and Daniel Watterson
Viruses 2021, 13(9), 1843; https://doi.org/10.3390/v13091843 - 15 Sep 2021
Cited by 1 | Viewed by 3267
Abstract
The use of dengue virus (DENV) vaccines has been hindered by the complexities of antibody dependent enhancement (ADE). Current late-stage vaccine candidates utilize attenuated and chimeric DENVs that produce particles of varying maturities. Antibodies that are elicited by preferentially exposed epitopes on immature [...] Read more.
The use of dengue virus (DENV) vaccines has been hindered by the complexities of antibody dependent enhancement (ADE). Current late-stage vaccine candidates utilize attenuated and chimeric DENVs that produce particles of varying maturities. Antibodies that are elicited by preferentially exposed epitopes on immature virions have been linked to increased ADE. We aimed to further understand the humoral immunity promoted by DENV particles of varying maturities in an AG129 mouse model using a chimeric insect specific vaccine candidate, bDENV-2. We immunized mice with mature, partially mature, and immature bDENV-2 and found that immunization with partially mature bDENV-2 produced more robust and cross-neutralizing immune responses than immunization with immature or mature bDENV-2. Upon challenge with mouse adapted DENV-2 (D220), we observed 80% protection for mature bDENV-2 vaccinated mice and 100% for immature and partially mature vaccinated mice, suggesting that protection to homotypic challenge is not dependent on maturation. Finally, we found reduced in vitro ADE at subneutralising serum concentrations for mice immunized with mature bDENV-2. These results suggest that both immature and mature DENV particles play a role in homotypic protection; however, the increased risk of in vitro ADE from immature particles indicates potential safety benefits from mature DENV-based vaccines. Full article
(This article belongs to the Special Issue Flavivirus Vaccines)
►▼ Show Figures

Figure 1

13 pages, 3823 KiB  
Article
Maternal Immunity and Vaccination Influence Disease Severity in Progeny in a Novel Mast Cell-Deficient Mouse Model of Severe Dengue
by Chinmay Kumar Mantri, Gayathri Soundarajan, Wilfried A. A. Saron, Abhay P. S. Rathore, Sylvie Alonso and Ashley L. St. John
Viruses 2021, 13(5), 900; https://doi.org/10.3390/v13050900 - 12 May 2021
Cited by 2 | Viewed by 3344
Abstract
Sub-neutralizing concentrations of antibodies in dengue infected patients is a major risk factor for the development of dengue hemorrhagic fever and dengue shock syndrome. Here, we describe a mouse model with a deficiency in mast cells (MCs) in addition to a deficiency in [...] Read more.
Sub-neutralizing concentrations of antibodies in dengue infected patients is a major risk factor for the development of dengue hemorrhagic fever and dengue shock syndrome. Here, we describe a mouse model with a deficiency in mast cells (MCs) in addition to a deficiency in Type-I and II IFN receptors for studying dengue virus (DENV) infection. We used this model to understand the influence of MCs in a maternal antibody-dependent model of severe dengue, where offspring born to DENV-immune mothers are challenged with a heterologous DENV serotype. Mice lacking both MCs and IFN receptors were found susceptible to primary DENV infection and showed morbidity and mortality. When these mice were immunized, pups born to DENV-immune mothers were found to be protected for a longer duration from a heterologous DENV challenge. In the absence of MCs and type-I interferon signaling, IFN-γ was found to protect pups born to naïve mothers but had the opposite effect on pups born to DENV-immune mothers. Our results highlight the complex interactions between MCs and IFN-signaling in influencing the role of maternal antibodies in DENV-induced disease severity. Full article
(This article belongs to the Special Issue Flavivirus Vaccines)
►▼ Show Figures

Figure 1

13 pages, 2748 KiB  
Article
Different Cross-Reactivities of IgM Responses in Dengue, Zika and Tick-Borne Encephalitis Virus Infections
by Karin Stiasny, Stefan Malafa, Stephan W. Aberle, Iris Medits, Georgios Tsouchnikas, Judith H. Aberle, Heidemarie Holzmann and Franz X. Heinz
Viruses 2021, 13(4), 596; https://doi.org/10.3390/v13040596 - 31 Mar 2021
Cited by 8 | Viewed by 2673
Abstract
Flaviviruses circulate worldwide and cause a number of medically relevant human diseases, such as dengue, Zika, yellow fever, and tick-borne encephalitis (TBE). Serology plays an important role in the diagnosis of flavivirus infections, but can be impeded by antigenic cross-reactivities among flaviviruses. Therefore, [...] Read more.
Flaviviruses circulate worldwide and cause a number of medically relevant human diseases, such as dengue, Zika, yellow fever, and tick-borne encephalitis (TBE). Serology plays an important role in the diagnosis of flavivirus infections, but can be impeded by antigenic cross-reactivities among flaviviruses. Therefore, serological diagnosis of a recent infection can be insufficiently specific, especially in areas where flaviviruses co-circulate and/or vaccination coverage against certain flaviviruses is high. In this study, we developed a new IgM assay format, which is well suited for the specific diagnosis of TBE, Zika and dengue virus infections. In the case of TBE and Zika, the IgM response proved to be highly specific for the infecting virus. In contrast, primary dengue virus infections induced substantial amounts of cross-reactive IgM antibodies, which is most likely explained by structural peculiarities of dengue virus particles. Despite the presence of cross-reactive IgM, the standardized nature and the quantitative read-out of the assay even allowed the serotype-specific diagnosis of recent dengue virus infections in most instances. Full article
(This article belongs to the Special Issue Flavivirus Vaccines)
►▼ Show Figures

Figure 1

15 pages, 628 KiB  
Article
Novel Flavivirus Attenuation Markers Identified in the Envelope Protein of Alfuy Virus
by Daniel Westlake, Helle Bielefeldt-Ohmann, Natalie A. Prow and Roy A. Hall
Viruses 2021, 13(2), 147; https://doi.org/10.3390/v13020147 - 20 Jan 2021
Cited by 4 | Viewed by 2409
Abstract
Alfuy (ALFV) is an attenuated flavivirus related to the Murray Valley encephalitis virus (MVEV). We previously identified markers of attenuation in the envelope (E) protein of the prototype strain (ALFV3929), including the hinge region (E273–277) and lack of glycosylation at E154-156. [...] Read more.
Alfuy (ALFV) is an attenuated flavivirus related to the Murray Valley encephalitis virus (MVEV). We previously identified markers of attenuation in the envelope (E) protein of the prototype strain (ALFV3929), including the hinge region (E273–277) and lack of glycosylation at E154-156. To further determine the mechanisms of attenuation we assessed ALFV3929 binding to glycosaminoglycans (GAG), a known mechanism of flaviviruses attenuation. Indeed, ALFV3929 exhibited reduced binding to GAG-rich cells in the presence of heparin; however, low-passage ALFV isolates were relatively unaffected. Sequence comparisons between ALFV strains and structural modelling incriminated a positively-charged residue (K327) in ALFV3929 as a GAG-binding motif. Substitution of this residue to the corresponding uncharged residue in MVEV (L), using a previously described chimeric virus containing the prM & E genes of ALFV3929 in the backbone of MVEV (MVEV/ALFV-prME), confirmed a role for K327 in enhanced GAG binding. When the wild type residues at E327, E273–277 and E154–156 of ALFV3929 were replaced with the corresponding residues from virulent MVEV, it revealed each motif contributed to attenuation of ALFV3929, with the E327/E273–277 combination most dominant. These data demonstrate that attenuation of ALFV3929 is multifactorial and provide new insights for the rational design of attenuated flavivirus vaccines. Full article
(This article belongs to the Special Issue Flavivirus Vaccines)
►▼ Show Figures

Figure 1

12 pages, 1819 KiB  
Article
Activation of an Effective Immune Response after Yellow Fever Vaccination Is Associated with the Genetic Background and Early Response of IFN-γ and CLEC5A
by Tamiris Azamor, Andréa Marques Vieira da Silva, Juliana Gil Melgaço, Ana Paula dos Santos, Caroline Xavier-Carvalho, Lucia Elena Alvarado-Arnez, Leonardo Ribeiro Batista-Silva, Denise Cristina de Souza Matos, Camilla Bayma, Sotiris Missailidis, Ana Paula Dinis Ano Bom, Milton Ozorio Moraes and Patrícia Cristina da Costa Neves
Viruses 2021, 13(1), 96; https://doi.org/10.3390/v13010096 - 12 Jan 2021
Cited by 10 | Viewed by 3383
Abstract
The yellow fever vaccine (YF17DD) is highly effective with a single injection conferring protection for at least 10 years. The YF17DD induces polyvalent responses, with a TH1/TH2 CD4+ profile, robust T CD8+ responses, and synthesis of interferon-gamma (IFN-γ), culminating in high [...] Read more.
The yellow fever vaccine (YF17DD) is highly effective with a single injection conferring protection for at least 10 years. The YF17DD induces polyvalent responses, with a TH1/TH2 CD4+ profile, robust T CD8+ responses, and synthesis of interferon-gamma (IFN-γ), culminating in high titers of neutralizing antibodies. Furthermore, C-type lectin domain containing 5A (CLEC5A) has been implicated in innate outcomes in other flaviviral infections. Here, we conducted a follow-up study in volunteers immunized with YF17DD, investigating the humoral response, cellular phenotypes, gene expression, and single nucleotide polymorphisms (SNPs) of IFNG and CLEC5A, to clarify the role of these factors in early response after vaccination. Activation of CLEC5A+ monocytes occurred five days after vaccination (DAV). Following, seven DAV data showed activation of CD4+ and CD8+T cells together with early positive correlations between type II IFN and genes of innate antiviral response (STAT1, STAT2, IRF7, IRF9, OAS1, and RNASEL) as well as antibody levels. Furthermore, individuals with genotypes rs2430561 AT/AA, rs2069718 AG/AA (IFNG), and rs13237944 AC/AA (CLEC5A), exhibited higher expression of IFNG and CLEC5A, respectively. Together, we demonstrated that early IFN-γ and CLEC5A responses, associated with rs2430561, rs2069718, and rs13237944 genotypes, may be key mechanisms in the long-lasting immunity elicited by YF17DD. Full article
(This article belongs to the Special Issue Flavivirus Vaccines)
►▼ Show Figures

Figure 1

14 pages, 3693 KiB  
Article
Identification of Novel Yellow Fever Class II Epitopes in YF-17D Vaccinees
by Jose Mateus, Alba Grifoni, Hannah Voic, Michael A. Angelo, Elizabeth Phillips, Simon Mallal, John Sidney, Alessandro Sette and Daniela Weiskopf
Viruses 2020, 12(11), 1300; https://doi.org/10.3390/v12111300 - 12 Nov 2020
Cited by 4 | Viewed by 3543
Abstract
Yellow fever virus (YFV) is a mosquito-borne member of the genus flavivirus, including other important human-pathogenic viruses, such as dengue, Japanese encephalitis, and Zika. Herein, we report identifying 129 YFV Class II epitopes in donors vaccinated with the live attenuated YFV vaccine (YFV-17D). [...] Read more.
Yellow fever virus (YFV) is a mosquito-borne member of the genus flavivirus, including other important human-pathogenic viruses, such as dengue, Japanese encephalitis, and Zika. Herein, we report identifying 129 YFV Class II epitopes in donors vaccinated with the live attenuated YFV vaccine (YFV-17D). A total of 1156 peptides predicted to bind 17 different common HLA-DRB1 allelic variants were tested using IFNγ ELISPOT assays in vitro re-stimulated peripheral blood mononuclear cells from twenty-six vaccinees. Overall, we detected responses against 215 YFV epitopes. We found that the capsid and envelope proteins, as well as the non-structural (NS) proteins NS3 and NS5, were the most targeted proteins by CD4+ T cells from YF-VAX vaccinated donors. In addition, we designed and validated by flow cytometry a CD4+ mega pool (MP) composed of structural and non-structural epitopes in an independent cohort of vaccinated donors. Overall, this study provides a comprehensive prediction and validation of YFV epitopes in a cohort of YF-17D vaccinated individuals. With the design of a CD4 epitope MP, we further provide a useful tool to detect ex vivo responses of YFV-specific CD4 T cells in small sample volumes. Full article
(This article belongs to the Special Issue Flavivirus Vaccines)
►▼ Show Figures

Figure 1

16 pages, 4029 KiB  
Article
Immune Reactivity of a 20-mer Peptide Representing the Zika E Glycan Loop Involves the Antigenic Determinants E-152/156/158
by Etienne Frumence, Juliano G. Haddad, Bénédicte Vanwalscappel, Jessica Andries, Jason Decotter, Wildriss Viranaicken, Gilles Gadea and Philippe Desprès
Viruses 2020, 12(11), 1258; https://doi.org/10.3390/v12111258 - 5 Nov 2020
Cited by 2 | Viewed by 2214
Abstract
Mosquito-borne Zika virus (ZIKV) causes a severe congenital syndrome and neurological disorders in humans. With the aim to develop a live-attenuated ZIKV strain, we generated a chimeric viral clone ZIKALIVax with African MR766-NIID strain as backbone and the envelope E protein of epidemic [...] Read more.
Mosquito-borne Zika virus (ZIKV) causes a severe congenital syndrome and neurological disorders in humans. With the aim to develop a live-attenuated ZIKV strain, we generated a chimeric viral clone ZIKALIVax with African MR766-NIID strain as backbone and the envelope E protein of epidemic Brazilian BeH810915 strain. The MR766-NIID residues E-T152/I156/Y158 were introduced into BeH810915 E protein leading to a nonglycosylated ZIKALIVax. Recently, we reported that the residues E-152/156/158 that are part of ZIKV glycan loop (GL) region might have an impact on the availability of neutralizing antibody epitopes on ZIKV surface. In the present study, we evaluated the antigenic reactivity of a synthetic 20-mer peptide representing the ZIKALIVax GL region. The GL-related peptide was effective for the detection of GL-reactive antibody in mouse anti-ZIKALIVax immune serum. We showed that the residue E-158 influences the antigenic reactivity of GL-related peptide. The ZIKALIVax peptide was effective in generating mouse antibodies with reactivity against a recombinant E domain I that encompasses the GL region. The GL peptide-reactive antibodies revealed that antigenic reactivity of E-domain I may be impacted by both residues E-152 and E-156. In conclusion, we proposed a role for the residues E-152/156/158 as key antigenic determinants of ZIKV glycan loop region. Full article
(This article belongs to the Special Issue Flavivirus Vaccines)
►▼ Show Figures

Figure 1

16 pages, 1293 KiB  
Article
Transcutaneous Administration of Dengue Vaccines
by Robert Andreata-Santos, Rúbens Prince dos Santos Alves, Sara Araujo Pereira, Lennon Ramos Pereira, Carla Longo de Freitas, Samuel Santos Pereira, Alexia Adrianne Venceslau-Carvalho, Maria Fernanda Castro-Amarante, Marianna Teixeira Pinho Favaro, Camila Mathias-Santos, Jaime Henrique Amorim and Luís Carlos de Souza Ferreira
Viruses 2020, 12(5), 514; https://doi.org/10.3390/v12050514 - 6 May 2020
Cited by 4 | Viewed by 3453
Abstract
In the present study, we evaluated the immunological responses induced by dengue vaccines under experimental conditions after delivery via a transcutaneous (TC) route. Vaccines against type 2 Dengue virus particles (DENV2 New Guinea C (NGC) strain) combined with enterotoxigenic Escherichia coli (ETEC) heat-labile [...] Read more.
In the present study, we evaluated the immunological responses induced by dengue vaccines under experimental conditions after delivery via a transcutaneous (TC) route. Vaccines against type 2 Dengue virus particles (DENV2 New Guinea C (NGC) strain) combined with enterotoxigenic Escherichia coli (ETEC) heat-labile toxin (LT) were administered to BALB/c mice in a three-dose immunization regimen via the TC route. As a control for the parenteral administration route, other mouse groups were immunized with the same vaccine formulation via the intradermic (ID) route. Our results showed that mice vaccinated either via the TC or ID routes developed similar protective immunity, as measured after lethal challenges with the DENV2 NGC strain. Notably, the vaccine delivered through the TC route induced lower serum antibody (IgG) responses with regard to ID-immunized mice, particularly after the third dose. The protective immunity elicited in TC-immunized mice was attributed to different antigen-specific antibody properties, such as epitope specificity and IgG subclass responses, and cellular immune responses, as determined by cytokine secretion profiles. Altogether, the results of the present study demonstrate the immunogenicity and protective properties of a dengue vaccine delivered through the TC route and offer perspectives for future clinical applications. Full article
(This article belongs to the Special Issue Flavivirus Vaccines)
►▼ Show Figures

Figure 1

Review

Jump to: Research

15 pages, 1060 KiB  
Review
Use of Animal Models in Studying Roles of Antibodies and Their Secretion Cells in Dengue Vaccine Development
by Kulkanya Chokephaibulkit, Yu-Wen Chien, Sazaly AbuBakar, Kovit Pattanapanyasat and Guey Chuen Perng
Viruses 2020, 12(11), 1261; https://doi.org/10.3390/v12111261 - 5 Nov 2020
Cited by 2 | Viewed by 2884
Abstract
The cardinal feature of adaptive immunity is its ability to form memory responses that can be rapidly recalled to contain pathogens upon reencountering. Conferring a robust memory immune response to an infection is a key feature for a successful vaccination program. The plasmablasts [...] Read more.
The cardinal feature of adaptive immunity is its ability to form memory responses that can be rapidly recalled to contain pathogens upon reencountering. Conferring a robust memory immune response to an infection is a key feature for a successful vaccination program. The plasmablasts are cells that not only can secret non-neutralizing antibodies but also can secrete the specific antibodies essential to neutralize and inactivate the invading pathogens. Dengue has been recognized as one of the most important vector-borne human viral diseases globally. Currently, supportive care with vigilant monitoring is the standard practice since there is as yet no approved therapeutic modality to treat dengue. Even though the approved vaccine has become available, its low efficacy with the potential to cause harm is the major hurdle to promote the widespread usage of the vaccine. Despite the decades of research on dengue, the major challenge in dengue vaccine development is the absence of suitable experimental animal models that reflect the pathological features and clinical symptoms, as seen in humans. Dengue is transmitted by the bite of mosquitoes carrying infectious dengue virus (DENV), which has four distinct serotypes. Recently, cases resulting from unconventional transmission routes, such as blood transfusion, organs as well as stem cells and bone marrow transplantations, and mother-to-infant vertical transmission, have been reported, suggesting an alternate route of DENV transmission exists in nature. This review discusses issues and challenges needing to be resolved to develop an effective dengue vaccine. Development of a robust and reliable dengue animal model that can reflect not only dynamic human clinical symptoms but also can answer around why preexisting neutralizing antibodies do not confer protection upon re-infection and immune protection marker for dengue vaccine efficacy evaluation. Full article
(This article belongs to the Special Issue Flavivirus Vaccines)
►▼ Show Figures

Figure 1

17 pages, 1689 KiB  
Review
The Effects of Pre-Existing Antibodies on Live-Attenuated Viral Vaccines
by Darren Z. L. Mok and Kuan Rong Chan
Viruses 2020, 12(5), 520; https://doi.org/10.3390/v12050520 - 8 May 2020
Cited by 48 | Viewed by 6698
Abstract
Live-attenuated vaccines (LAVs) have achieved remarkable successes in controlling virus spread, as well as for other applications such as cancer immunotherapy. However, with rapid increases in international travel, globalization, geographic spread of viral vectors, and widespread use of vaccines, there is an increasing [...] Read more.
Live-attenuated vaccines (LAVs) have achieved remarkable successes in controlling virus spread, as well as for other applications such as cancer immunotherapy. However, with rapid increases in international travel, globalization, geographic spread of viral vectors, and widespread use of vaccines, there is an increasing need to consider how pre-exposure to viruses which share similar antigenic regions can impact vaccine efficacy. Pre-existing antibodies, derived from either from maternal–fetal transmission, or by previous infection or vaccination, have been demonstrated to interfere with vaccine immunogenicity of measles, adenovirus, and influenza LAVs. Immune interference of LAVs can be caused by the formation of virus–antibody complexes that neutralize virus infection in antigen-presenting cells, or by the cross-linking of the B-cell receptor with the inhibitory receptor, FcγRIIB. On the other hand, pre-existing antibodies can augment flaviviral LAV efficacy such as that of dengue and yellow fever virus, especially when pre-existing antibodies are present at sub-neutralizing levels. The increased vaccine immunogenicity can be facilitated by antibody-dependent enhancement of virus infection, enhancing virus uptake in antigen-presenting cells, and robust induction of innate immune responses that promote vaccine immunogenicity. This review examines the literature on this topic and examines the circumstances where pre-existing antibodies can inhibit or enhance LAV efficacy. A better knowledge of the underlying mechanisms involved could allow us to better manage immunization in seropositive individuals and even identify possibilities that could allow us to exploit pre-existing antibodies to boost vaccine-induced responses for improved vaccine efficacy. Full article
(This article belongs to the Special Issue Flavivirus Vaccines)
►▼ Show Figures

Graphical abstract

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-11
Back to TopTop