Vaccines against RNA Viruses

A special issue of Vaccines (ISSN 2076-393X).

Deadline for manuscript submissions: closed (31 December 2019) | Viewed by 53214

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Guest Editor
ZOOVIR, Department of Biotechnology, Instituto Nacional de Investigaciones Agrarias (INIA), 28040 Madrid, Spain
Interests: RNA viruses; Flavivirus; host-cell interactions; surveillance and prevention (diagnosis, epidemiology, vaccines and antivirals)
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Special Issue Information

Dear Colleagues,

As the Guest Editor of the Vaccines Special Issue “Vaccines against RNA Viruses” (https://www.mdpi.com/journal/vaccines/special_issues), I would like to invite you to contribute with an original report, original observation, or review to it.

As you are perfectly aware, RNA viruses cause many animal, human, and zoonotic diseases, affecting millions of individuals. In this regard, vaccines have had an enormous impact on overcoming the global burden of diseases. However, and although efficient vaccines are available for some RNA viruses, in many instances and for different reasons (technologic restrictions, economic facts, etc.), they are scarcely used in the field, and, even more, for many of them, no licensed vaccines are available. Therefore, as the world remains burdened by high morbidity and mortality diseases and new emerging or re-emerging pathogens are likely to spread in the future, to achieve a more comprehensive understanding of the current trends in vaccines development and assessment, this Vaccines Special Issue is dedicated to recent search for efficient vaccines, focusing on the scientific and technical progress made in the field of vaccines targeting RNA viruses, as well as in understanding the molecular mechanisms and immune responses involved. Based on your extensive experience and your recent publications, it will be our honor to publish your quality work to support the global scientific community. We sincerely hope that you will be able to accept our invitation. If you are able to contribute, please let us know at your earliest convenience and we will provide you with additional details.

Vaccines (https://www.mdpi.com/journal/vaccines) is an online open access journal covering vaccine-related sciences, indexed in the Science Citation Index Expanded (SCIE) and BIOSIS Previews in Web of Science and in Scopus. Citations available in PubMed, full-text archived in PubMed Central. CiteScore 2018 (Scopus): 5.43, which equals rank 12/272 (Q1) in the category 'Infectious Diseases', 31/198 (Q1) in 'Immunology', and 4/232 (Q1) in 'Pharmacology (medical)'. Manuscripts are peer-reviewed and a first decision provided to authors approximately 17.7 days after submission; acceptance to publication is undertaken in 4.4 days (median values for papers published in this journal in the second half of 2018), assuring rapid publication.

Sincerely

Prof. Dr. Juan Carlos Saiz
Guest Editors

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Keywords

  • human vaccines
  • veterinary vaccines
  • zoonotic virus vaccines
  • vaccine platforms
  • animal models
  • immune responses
  • effectiveness
  • trials
  • maternal immunization
  • public health considerations

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Published Papers (10 papers)

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Editorial

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4 pages, 171 KiB  
Editorial
Vaccines against RNA Viruses
by Juan-Carlos Saiz
Vaccines 2020, 8(3), 479; https://doi.org/10.3390/vaccines8030479 - 27 Aug 2020
Cited by 3 | Viewed by 3322
Abstract
RNA viruses cause animal, human, and zoonotic diseases that affect millions of individuals, as is being exemplified by the devastating ongoing epidemic of the recently identified SARS-Cov-2 [...] Full article
(This article belongs to the Special Issue Vaccines against RNA Viruses)

Research

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13 pages, 1850 KiB  
Article
Broad Protection of Pigs against Heterologous PRRSV Strains by a GP5-Mosaic DNA Vaccine Prime/GP5-Mosaic rVaccinia (VACV) Vaccine Boost
by Junru Cui, Caitlin M. O’Connell, Connor Hagen, Kim Sawicki, Joan A. Smyth, Paulo H. Verardi, Herbert J. Van Kruiningen and Antonio E. Garmendia
Vaccines 2020, 8(1), 106; https://doi.org/10.3390/vaccines8010106 - 28 Feb 2020
Cited by 13 | Viewed by 4297
Abstract
Background: Porcine reproductive and respiratory syndrome (PRRS) viruses are a major cause of disease and economic loss in pigs worldwide. High genetic diversity among PRRSV strains is problematic for successful disease control by vaccination. Mosaic DNA and vaccinia (VACV) vaccines were developed in [...] Read more.
Background: Porcine reproductive and respiratory syndrome (PRRS) viruses are a major cause of disease and economic loss in pigs worldwide. High genetic diversity among PRRSV strains is problematic for successful disease control by vaccination. Mosaic DNA and vaccinia (VACV) vaccines were developed in order to improve protection against heterologous PRRSV strains. Methods: Piglets were primed and boosted with GP5-Mosaic DNA vaccine and recombinant GP5-Mosaic VACV (rGP5-Mosaic VACV), respectively. Pigs vaccinated with rGP5-WT (VR2332) DNA and rGP5-WT VACV, or empty vector DNA and empty VACV respectively, served as controls. Virus challenge was given to separate groups of vaccinated pigs with VR2332 or MN184C. Necropsies were performed 14 days after challenge. Results: Vaccination with the GP5-Mosaic-based vaccines resulted in cellular reactivity and higher levels of neutralizing antibodies to both VR2332 and MN184C PRRSV strains. In contrast, vaccination of animals with the GP5-WT vaccines induced responses only to VR2332. Furthermore, vaccination with the GP5-Mosaic based vaccines resulted in protection against challenge with two heterologous virus strains, as demonstrated by the significantly lower viral loads in serum, tissues, porcine alveolar macrophages (PAMs), and bronchoalveolar lavage (BAL) fluids, and less severe lung lesions after challenge with either MN184C or VR2332, which have only 85% identity. In contrast, significant protection by the GP5-WT based vaccines was only achieved against the VR2332 strain. Conclusions: GP5-Mosaic vaccines, using a DNA-prime/VACV boost regimen, conferred protection in pigs against heterologous viruses. Full article
(This article belongs to the Special Issue Vaccines against RNA Viruses)
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15 pages, 2808 KiB  
Article
MVA Vectored Vaccines Encoding Rift Valley Fever Virus Glycoproteins Protect Mice against Lethal Challenge in the Absence of Neutralizing Antibody Responses
by Elena López-Gil, Sandra Moreno, Javier Ortego, Belén Borrego, Gema Lorenzo and Alejandro Brun
Vaccines 2020, 8(1), 82; https://doi.org/10.3390/vaccines8010082 - 12 Feb 2020
Cited by 13 | Viewed by 2952
Abstract
In vitro neutralizing antibodies have been often correlated with protection against Rift Valley fever virus (RVFV) infection. We have reported previously that a single inoculation of sucrose-purified modified vaccinia Ankara (MVA) encoding RVFV glycoproteins (rMVAGnGc) was sufficient to induce a protective immune response [...] Read more.
In vitro neutralizing antibodies have been often correlated with protection against Rift Valley fever virus (RVFV) infection. We have reported previously that a single inoculation of sucrose-purified modified vaccinia Ankara (MVA) encoding RVFV glycoproteins (rMVAGnGc) was sufficient to induce a protective immune response in mice after a lethal RVFV challenge. Protection was related to the presence of glycoprotein specific CD8+ cells, with a low-level detection of in vitro neutralizing antibodies. In this work we extended those observations aimed to explore the role of humoral responses after MVA vaccination and to study the contribution of each glycoprotein antigen to the protective efficacy. Thus, we tested the efficacy and immune responses in BALB/c mice of recombinant MVA viruses expressing either glycoprotein Gn (rMVAGn) or Gc (rMVAGc). In the absence of serum neutralizing antibodies, our data strongly suggest that protection of vaccinated mice upon the RVFV challenge can be achieved by the activation of cellular responses mainly directed against Gc epitopes. The involvement of cellular immunity was stressed by the fact that protection of mice was strain dependent. Furthermore, our data suggest that the rMVA based single dose vaccination elicits suboptimal humoral immune responses against Gn antigen since disease in mice was exacerbated upon virus challenge in the presence of rMVAGnGc or rMVAGn immune serum. Thus, Gc-specific cellular immunity could be an important component in the protection after the challenge observed in BALB/c mice, contributing to the elimination of infected cells reducing morbidity and mortality and counteracting the deleterious effect of a subneutralizing antibody immune response. Full article
(This article belongs to the Special Issue Vaccines against RNA Viruses)
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17 pages, 2065 KiB  
Article
Differential Immune Transcriptome and Modulated Signalling Pathways in Rainbow Trout Infected with Viral Haemorrhagic Septicaemia Virus (VHSV) and Its Derivative Non-Virion (NV) Gene Deleted
by Blanca Chinchilla, Paloma Encinas, Julio M. Coll and Eduardo Gomez-Casado
Vaccines 2020, 8(1), 58; https://doi.org/10.3390/vaccines8010058 - 30 Jan 2020
Cited by 17 | Viewed by 3753
Abstract
Viral haemorrhagic septicaemia virus (VHSV) is one of the worst viral threats to fish farming. Non-virion (NV) gene-deleted VHSV (dNV-VHSV) has been postulated as an attenuated virus, because the absence of the NV gene leads to lower induced pathogenicity. However, little is known [...] Read more.
Viral haemorrhagic septicaemia virus (VHSV) is one of the worst viral threats to fish farming. Non-virion (NV) gene-deleted VHSV (dNV-VHSV) has been postulated as an attenuated virus, because the absence of the NV gene leads to lower induced pathogenicity. However, little is known about the immune responses driven by dNV-VHSV and the wild-type (wt)-VHSV in the context of infection. Here, we obtained the immune transcriptome profiling in trout infected with dNV-VHSV and wt-VHSV and the pathways involved in immune responses. As general results, dNV-VHSV upregulated more trout immune genes than wt-VHSV (65.6% vs 45.7%, respectively), whereas wt-VHSV maintained more non-regulated genes than dNV-VHSV (45.7% vs 14.6%, respectively). The modulated pathways analysis (Gene-Set Enrichment Analysis, GSEA) showed that, when compared to wt-VHSV infected trout, the dNV-VHSV infected trout upregulated signalling pathways (n = 19) such as RIG-I (retinoic acid-inducible gene-I) like receptor signalling, Toll-like receptor signalling, type II interferon signalling, and nuclear factor kappa B (NF-kappa B) signalling, among others. The results from individual genes and GSEA demonstrated that wt-VHSV impaired the activation at short stages of infection of pro-inflammatory, antiviral, proliferation, and apoptosis pathways, delaying innate humoral response and cellular crosstalk, whereas dNV-VHSV promoted the opposite effects. Therefore, these results might support future studies on using dNV-VHSV as a potential live vaccine. Full article
(This article belongs to the Special Issue Vaccines against RNA Viruses)
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11 pages, 756 KiB  
Article
A Single Dose of Dendrimer B2T Peptide Vaccine Partially Protects Pigs against Foot-and-Mouth Disease Virus Infection
by Rodrigo Cañas-Arranz, Mar Forner, Sira Defaus, Patricia de León, María J. Bustos, Elisa Torres, Francisco Sobrino, David Andreu and Esther Blanco
Vaccines 2020, 8(1), 19; https://doi.org/10.3390/vaccines8010019 - 10 Jan 2020
Cited by 20 | Viewed by 3952
Abstract
Foot-and-mouth disease virus (FMDV) causes a highly contagious disease of cloven-hoofed animals whose control relies on efficient vaccination. We have reported that dendrimer peptide B2T, with two copies of FMDV B-cell epitope VP1 (136–154) linked through maleimide units to T-cell epitope [...] Read more.
Foot-and-mouth disease virus (FMDV) causes a highly contagious disease of cloven-hoofed animals whose control relies on efficient vaccination. We have reported that dendrimer peptide B2T, with two copies of FMDV B-cell epitope VP1 (136–154) linked through maleimide units to T-cell epitope 3A (21–35)], elicits potent B- and T-cell specific responses and confers solid protection in pigs to type-O FMDV challenge after two doses of peptide. Herein we now show that B2T evokes specific protective immune responses after administration of a single dose of either 2 or 0.5 mg of peptide. High titers of ELISA and neutralizing antibodies against FMDV were detectable at day 15 post-immunization. Likewise, activated T cells and induced IFN-γ response to in vitro recall with FMDV peptides were also detected by the same day. Further, in 70% of B2T-vaccinated pigs, full protection—no clinical signs of disease—was observed upon virus challenge at day 25 post-immunization. These results strengthen the potential of B2T as a safe, cost-effective candidate vaccine conferring adequate protection against FMDV with a single dose. The finding is particularly relevant to emergency scenarios permitting only a single shot immunization. Full article
(This article belongs to the Special Issue Vaccines against RNA Viruses)
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14 pages, 1051 KiB  
Article
Parenterally Administered P24-VP8* Nanoparticle Vaccine Conferred Strong Protection against Rotavirus Diarrhea and Virus Shedding in Gnotobiotic Pigs
by Ashwin Ramesh, Jiangdi Mao, Shaohua Lei, Erica Twitchell, Ashton Shiraz, Xi Jiang, Ming Tan and Lijuan Yuan
Vaccines 2019, 7(4), 177; https://doi.org/10.3390/vaccines7040177 - 6 Nov 2019
Cited by 20 | Viewed by 4389
Abstract
Current live rotavirus vaccines are costly with increased risk of intussusception due to vaccine replication in the gut of vaccinated children. New vaccines with improved safety and cost-effectiveness are needed. In this study, we assessed the immunogenicity and protective efficacy of a novel [...] Read more.
Current live rotavirus vaccines are costly with increased risk of intussusception due to vaccine replication in the gut of vaccinated children. New vaccines with improved safety and cost-effectiveness are needed. In this study, we assessed the immunogenicity and protective efficacy of a novel P24-VP8* nanoparticle vaccine using the gnotobiotic (Gn) pig model of human rotavirus infection and disease. Three doses of P24-VP8* (200 μg/dose) intramuscular vaccine with Al(OH)3 adjuvant (600 μg) conferred significant protection against infection and diarrhea after challenge with virulent Wa strain rotavirus. This was indicated by the significant reduction in the mean duration of diarrhea, virus shedding in feces, and significantly lower fecal cumulative consistency scores in post-challenge day (PCD) 1–7 among vaccinated pigs compared to the mock immunized controls. The P24-VP8* vaccine was highly immunogenic in Gn pigs. It induced strong VP8*-specific serum IgG and Wa-specific virus-neutralizing antibody responses from post-inoculation day 21 to PCD 7, but did not induce serum or intestinal IgA antibody responses or a strong effector T cell response, which are consistent with the immunization route, the adjuvant used, and the nature of the non-replicating vaccine. The findings are highly translatable and thus will facilitate clinical trials of the P24-VP8* nanoparticle vaccine. Full article
(This article belongs to the Special Issue Vaccines against RNA Viruses)
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12 pages, 2674 KiB  
Article
Significant Interference with Porcine Epidemic Diarrhea Virus Pandemic and Classical Strain Replication in Small-Intestine Epithelial Cells Using an shRNA Expression Vector
by Da Shi, Xiaobo Wang, Hongyan Shi, Jiyu Zhang, Yuru Han, Jianfei Chen, Xin Zhang, Jianbo Liu, Jialin Zhang, Zhaoyang Ji, Zhaoyang Jing and Li Feng
Vaccines 2019, 7(4), 173; https://doi.org/10.3390/vaccines7040173 - 2 Nov 2019
Cited by 3 | Viewed by 3403
Abstract
Porcine epidemic diarrhea (PED) re-emerged in China in 2010 and is now widespread. Evidence indicates that highly virulent porcine epidemic diarrhea virus (PEDV) strains belonging to genotype G2 caused a large-scale outbreak of diarrhea. Currently, vaccines derived from PEDV classical strains do not [...] Read more.
Porcine epidemic diarrhea (PED) re-emerged in China in 2010 and is now widespread. Evidence indicates that highly virulent porcine epidemic diarrhea virus (PEDV) strains belonging to genotype G2 caused a large-scale outbreak of diarrhea. Currently, vaccines derived from PEDV classical strains do not effectively prevent infection by virulent PEDV strains, and no specific drug is available to treat the disease. RNA interference (RNAi) is a novel and effective way to cure a wide range of viruses. We constructed three short hairpin RNA (shRNA)-expressing plasmids (shR-N307, shR-N463, and shR-N1071) directed against nucleocapsid (N) and determined their antiviral activities in intestine epithelial cells infected with a classical CV777 strain and LNCT2. We verified that shR-N307, shR-N463, and shR-N1071 effectively inhibited the expression of the transfected N gene in vitro, comparable to the control shRNA. We further demonstrated the shRNAs markedly reduced PEDV CV777 and LNCT2 replication upon downregulation of N production. Therefore, this study provides a new strategy for the design of antiviral methods against coronaviruses by targeting their processivity factors. Full article
(This article belongs to the Special Issue Vaccines against RNA Viruses)
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18 pages, 2336 KiB  
Article
Artificial Anti-HIV-1 Immunogen Comprising Epitopes of Broadly Neutralizing Antibodies 2F5, 10E8, and a Peptide Mimic of VRC01 Discontinuous Epitope
by Andrey P. Rudometov, Anton N. Chikaev, Nadezhda B. Rudometova, Denis V. Antonets, Alexander A. Lomzov, Olga N. Kaplina, Alexander A. Ilyichev and Larisa I. Karpenko
Vaccines 2019, 7(3), 83; https://doi.org/10.3390/vaccines7030083 - 6 Aug 2019
Cited by 9 | Viewed by 5973
Abstract
The construction of artificial proteins using conservative B-cell and T-cell epitopes is believed to be a promising approach for a vaccine design against diverse viral infections. This article describes the development of an artificial HIV-1 immunogen using a polyepitope immunogen design strategy. We [...] Read more.
The construction of artificial proteins using conservative B-cell and T-cell epitopes is believed to be a promising approach for a vaccine design against diverse viral infections. This article describes the development of an artificial HIV-1 immunogen using a polyepitope immunogen design strategy. We developed a recombinant protein, referred to as nTBI, that contains epitopes recognized by broadly neutralizing HIV-1 antibodies (bNAbs) combined with Th-epitopes. This is a modified version of a previously designed artificial protein, TBI (T- and B-cell epitopes containing Immunogen), carrying four T- and five B-cell epitopes from HIV-1 Env and Gag proteins. To engineer the nTBI molecule, three B-cell epitopes of the TBI protein were replaced with the epitopes recognized by broadly neutralizing HIV-1 antibodies 10E8, 2F5, and a linear peptide mimic of VRC01 epitope. We showed that immunization of rabbits with the nTBI protein elicited antibodies that recognize HIV-1 proteins and were able to neutralize Env-pseudotyped SF162.LS HIV-1 strain (tier 1). Competition assay revealed that immunization of rabbits with nTBI induced mainly 10E8-like antibodies. Our findings support the use of nTBI protein as an immunogen with predefined favorable antigenic properties. Full article
(This article belongs to the Special Issue Vaccines against RNA Viruses)
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Review

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23 pages, 790 KiB  
Review
Hepatitis C Virus Vaccine: Challenges and Prospects
by Joshua D. Duncan, Richard A. Urbanowicz, Alexander W. Tarr and Jonathan K. Ball
Vaccines 2020, 8(1), 90; https://doi.org/10.3390/vaccines8010090 - 17 Feb 2020
Cited by 59 | Viewed by 11285
Abstract
The hepatitis C virus (HCV) causes both acute and chronic infection and continues to be a global problem despite advances in antiviral therapeutics. Current treatments fail to prevent reinfection and remain expensive, limiting their use to developed countries, and the asymptomatic nature of [...] Read more.
The hepatitis C virus (HCV) causes both acute and chronic infection and continues to be a global problem despite advances in antiviral therapeutics. Current treatments fail to prevent reinfection and remain expensive, limiting their use to developed countries, and the asymptomatic nature of acute infection can result in individuals not receiving treatment and unknowingly spreading HCV. A prophylactic vaccine is therefore needed to control this virus. Thirty years since the discovery of HCV, there have been major gains in understanding the molecular biology and elucidating the immunological mechanisms that underpin spontaneous viral clearance, aiding rational vaccine design. This review discusses the challenges facing HCV vaccine design and the most recent and promising candidates being investigated. Full article
(This article belongs to the Special Issue Vaccines against RNA Viruses)
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23 pages, 2588 KiB  
Review
Current Progress of Avian Vaccines Against West Nile Virus
by Nereida Jiménez de Oya, Estela Escribano-Romero, Ana-Belén Blázquez, Miguel A. Martín-Acebes and Juan-Carlos Saiz
Vaccines 2019, 7(4), 126; https://doi.org/10.3390/vaccines7040126 - 23 Sep 2019
Cited by 17 | Viewed by 5424
Abstract
Birds are the main natural host of West Nile virus (WNV), the worldwide most distributed mosquito-borne flavivirus, but humans and equids can also be sporadic hosts. Many avian species have been reported as susceptible to WNV, particularly corvids. In the case that clinical [...] Read more.
Birds are the main natural host of West Nile virus (WNV), the worldwide most distributed mosquito-borne flavivirus, but humans and equids can also be sporadic hosts. Many avian species have been reported as susceptible to WNV, particularly corvids. In the case that clinical disease develops in birds, this is due to virus invasion of different organs: liver, spleen, kidney, heart, and mainly the central nervous system, which can lead to death 24–48 h later. Nowadays, vaccines have only been licensed for use in equids; thus, the availability of avian vaccines would benefit bird populations, both domestic and wild ones. Such vaccines could be used in endangered species housed in rehabilitation and wildlife reserves, and in animals located at zoos and other recreational installations, but also in farm birds, and in those that are grown for hunting and restocking activities. Even more, controlling WNV infection in birds can also be useful to prevent its spread and limit outbreaks. So far, different commercial and experimental vaccines (inactivated, attenuated, and recombinant viruses, and subunits and DNA-based candidates) have been evaluated, with various regimens, both in domestic and wild avian species. However, there are still disadvantages that must be overcome before avian vaccination can be implemented, such as its cost-effectiveness for domestic birds since in many species the pathogenicity is low or zero, or the viability of being able to achieve collective immunity in wild birds in freedom. Here, a comprehensive review of what has been done until now in the field of avian vaccines against WNV is presented and discussed. Full article
(This article belongs to the Special Issue Vaccines against RNA Viruses)
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