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Pathogenesis of Viral Infections: Implications in the Development of Vaccines...
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Pathogenesis of Viral Infections: Implications in the Development of Vaccines and Diagnostic Tools

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 July 2022) | Viewed by 13917

Special Issue Editors

Dr. Llilianne Ganges

E-Mail Website
Guest Editor
OIE Reference Laboratory for Classical Swine Fever, Institute of Agrifood Research and Technology (IRTA), Centre de Recerca en Sanitat Animal (CReSA), Campus de la Universitat Autònoma de Barcelona, 08193 Barcelona, Spain
Interests: virology; viral pathogenesis and immunology; innate and adaptive immunity; virus host interaction; viral evolution; vaccine and diagnostic tools design; viruses in animal health
Special Issues, Collections and Topics in MDPI journals
Dr. Jishu Shi

E-Mail Website
Guest Editor
Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA
Interests: vaccine; adjuvants; diagnostic assays; swine viruses; classical swine fever; African swine fever; vaccine immunology; PRRS; vaccine efficacy testing
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue focuses on gathering articles that show the most relevant aspects of viral pathogenesis that constitute novel and strategic targets for the development of vaccines and diagnostic methods of relevant diseases that affect animal health. We will focus on the mechanisms of viral persistence, specifically virus–host interactions, immunology, and immunopathology. The prevention and rapid detection capacity of possible new virus emergencies that may affect animal and human health is one of the great challenges that we must face in the near future. The development of rapid and cost-effective diagnostic methods, as well as new vaccine strategies, will be key tools to overcome these challenges. Fundamental and applied research in immunology and vaccinology will also be collected in this issue.

Dr. Llilianne Ganges
Dr. Jishu Shi
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

  • innate and adaptive immunity
  • vaccine development
  • oral vaccination
  • virus diagnostic
  • emerging virus
  • next-generation sequencing
  • virus variant detection
  • viruses in animal health

Published Papers (7 papers)

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Research

19 pages, 2692 KiB  
Article
Carboxyl-Terminal Decoy Epitopes in the Capsid Protein of Porcine Circovirus Type 2 Are Immunogenicity-Enhancers That Elicit Predominantly Specific Antibodies in Non-Vaccinated Pigs
by Ling-Chu Hung
Viruses 2022, 14(11), 2373; https://0-doi-org.brum.beds.ac.uk/10.3390/v14112373 - 27 Oct 2022
Cited by 1 | Viewed by 1204
Abstract
In the context of the carboxyl-terminus (C-terminus) of the capsid protein of porcine circovirus type 2a (PCV2a) and PCV2a vaccines, this study aimed to explore its unrevealing cryptic epitope and its relation to PCV2-infected herd immunity. To discover the C-terminus of the capsid [...] Read more.
In the context of the carboxyl-terminus (C-terminus) of the capsid protein of porcine circovirus type 2a (PCV2a) and PCV2a vaccines, this study aimed to explore its unrevealing cryptic epitope and its relation to PCV2-infected herd immunity. To discover the C-terminus of the capsid protein of PCV2a, monoclonal antibodies (mAbs) were generated in this work. Two mAbs bound the two minimal linear epitopes (229PPLKP233 and 228DPPLNP233 (or 229PPLNP233)), which were located at the C-terminus of the capsid proteins of PCV2a and PCV2b, respectively. One mAb bound to the minimal linear epitope (220QFREFNLK227, peptide P82), but it neither bound the virus-like particle (VLP) of PCV2a nor produced positive staining in PCV2a-infected cells by immunofluorescence assay. Further, the residues 220–227 were not accessible on the surface of the VLP on the three-dimensional model, but the residues 228–231 extend toward the VLP exterior. Immunoassays were conducted in this study to screen anti-viral peptide-specific IgGs, which could differentiate vaccinated pigs from non-vaccinated ones. The data show two 220QFREFNLKDPPLKP233-containing peptides had a significantly higher binding reactivity with sera from PCV2-infected pigs in the control group than with sera from the VLP-vaccine group, particularly seen in sera from swine aged 15 weeks to 24 weeks. However, the peptide P82 had not this phenomenon in that test. This study confirmed that C-terminal epitopes play an important role in PCV2-induced decoy of swine humoral immunity. Full article
(This article belongs to the Special Issue Pathogenesis of Viral Infections: Implications in the Development of Vaccines and Diagnostic Tools)
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24 pages, 3819 KiB  
Article
Evolution of Swine Influenza Virus H3N2 in Vaccinated and Nonvaccinated Pigs after Previous Natural H1N1 Infection
by Álvaro López-Valiñas, Laura Baioni, Lorena Córdoba, Ayub Darji, Chiara Chiapponi, Joaquim Segalés, Llilianne Ganges and José I. Núñez
Viruses 2022, 14(9), 2008; https://0-doi-org.brum.beds.ac.uk/10.3390/v14092008 - 10 Sep 2022
Cited by 2 | Viewed by 2366
Abstract
Swine influenza viruses (SIV) produce a highly contagious and worldwide distributed disease that can cause important economic losses to the pig industry. Currently, this virus is endemic in farms and, although used limitedly, trivalent vaccine application is the most extended strategy to control [...] Read more.
Swine influenza viruses (SIV) produce a highly contagious and worldwide distributed disease that can cause important economic losses to the pig industry. Currently, this virus is endemic in farms and, although used limitedly, trivalent vaccine application is the most extended strategy to control SIV. The presence of pre-existing immunity against SIV may modulate the evolutionary dynamic of this virus. To better understand these dynamics, the viral variants generated in vaccinated and nonvaccinated H3N2 challenged pigs after recovery from a natural A(H1N1) pdm09 infection were determined and analyzed. In total, seventeen whole SIV genomes were determined, 6 from vaccinated, and 10 from nonvaccinated animals and their inoculum, by NGS. Herein, 214 de novo substitutions were found along all SIV segments, 44 of them being nonsynonymous ones with an allele frequency greater than 5%. Nonsynonymous substitutions were not found in NP; meanwhile, many of these were allocated in PB2, PB1, and NS1 proteins. Regarding HA and NA proteins, higher nucleotide diversity, proportionally more nonsynonymous substitutions with an allele frequency greater than 5%, and different domain allocations of mutants, were observed in vaccinated animals, indicating different evolutionary dynamics. This study highlights the rapid adaptability of SIV in different environments. Full article
(This article belongs to the Special Issue Pathogenesis of Viral Infections: Implications in the Development of Vaccines and Diagnostic Tools)
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16 pages, 2633 KiB  
Article
The FlagT4G Vaccine Confers a Strong and Regulated Immunity and Early Virological Protection against Classical Swine Fever
by José Alejandro Bohórquez, Miaomiao Wang, Ivan Díaz, Mònica Alberch, Marta Pérez-Simó, Rosa Rosell, Douglas P. Gladue, Manuel V. Borca and Llilianne Ganges
Viruses 2022, 14(9), 1954; https://0-doi-org.brum.beds.ac.uk/10.3390/v14091954 - 02 Sep 2022
Cited by 1 | Viewed by 1711
Abstract
Control of classical swine fever virus (CSFV) in endemic countries relies on vaccination, mostly using vaccines that do not allow for differentiation of vaccinated from infected animals (DIVA). FlagT4G vaccine is a novel candidate that confers robust immunity and shows DIVA capabilities. The [...] Read more.
Control of classical swine fever virus (CSFV) in endemic countries relies on vaccination, mostly using vaccines that do not allow for differentiation of vaccinated from infected animals (DIVA). FlagT4G vaccine is a novel candidate that confers robust immunity and shows DIVA capabilities. The present study assessed the immune response elicited by FlagT4G and its capacity to protect pigs for a short time after vaccination. Five days after a single dose of FlagT4G vaccine, animals were challenged with a highly virulent CSFV strain. A strong, but regulated, interferon-α response was found after vaccination. Vaccinated animals showed clinical and virological protection against the challenge, in the absence of antibody response at 5 days post-vaccination. Upon challenge, a rapid rise in the titers of CSFV neutralizing antibodies and an increase in the IFN-γ producing cells were noticed in all vaccinated-challenged pigs. Meanwhile, unvaccinated pigs showed severe clinical signs and high viral replication, being euthanized before the end of the trial. These animals were unable to generate neutralizing antibodies and IFN-γ responses after the CSFV challenge. The results from the present study assert the fast and efficient protection by FlagT4G, a highly promising tool for CSFV control worldwide. Full article
(This article belongs to the Special Issue Pathogenesis of Viral Infections: Implications in the Development of Vaccines and Diagnostic Tools)
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17 pages, 22803 KiB  
Article
Development of Novel Recombinant Antigens of Nucleoprotein and Matrix Proteins of Porcine orthorubulavirus: Antigenicity and Structural Prediction
by Rocío Lara-Romero, José Luis Cerriteño-Sánchez, Susana Mendoza-Elvira, José Bryan García-Cambrón, María Azucena Castañeda-Montes, José Manuel Pérez-Aguilar and Julieta Sandra Cuevas-Romero
Viruses 2022, 14(9), 1946; https://0-doi-org.brum.beds.ac.uk/10.3390/v14091946 - 01 Sep 2022
Cited by 4 | Viewed by 1720
Abstract
Blue eye disease (BED) is a swine viral infection that affects the pork industry of Mexico. Porcine orthorubulavirus (PRV) is the etiological agent, and the hemagglutinin-neuraminidase protein (HN) is characterized as the best antigen for serological tests, although other structural proteins, including the [...] Read more.
Blue eye disease (BED) is a swine viral infection that affects the pork industry of Mexico. Porcine orthorubulavirus (PRV) is the etiological agent, and the hemagglutinin-neuraminidase protein (HN) is characterized as the best antigen for serological tests, although other structural proteins, including the nucleoprotein (NP) and the matrix (M) protein, have been investigated during the infection of members of the Paramyxoviridae family, generating promising results. Herein, for the first time, we successfully produced and characterized both the NP and M proteins of PRV by using a recombinant strategy in the E. coli heterologous system. The ORF of the NP and M genes were cloned in-frame with the pET-SUMO expression vector. Recombinant proteins proved to be a sensitive target to detect seroconversion at 7 days until 28 days in vaccinated mice (BALB/c) by indirect ELISAs. Immunoreactivity was also tested using porcine serum samples, in which antibodies were recognized from early stages to a persistence of PRV infection, which is indicative that these proteins contain properties similar to native antigens. The predicted tertiary structure showed that both proteins have a conserved structure that resembles those found in others Paramyxovirus. Our results pave the way for developing biotechnological tools based on these proteins for the control and prevention of BED. Full article
(This article belongs to the Special Issue Pathogenesis of Viral Infections: Implications in the Development of Vaccines and Diagnostic Tools)
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11 pages, 2047 KiB  
Article
A Novel Competitive ELISA for Specifically Measuring and Differentiating Immune Responses to Classical Swine Fever C-Strain Vaccine in Pigs
by Lihua Wang, Shijiang Mi, Rachel Madera, Yuzhen Li, Wenjie Gong, Changchun Tu and Jishu Shi
Viruses 2022, 14(7), 1544; https://0-doi-org.brum.beds.ac.uk/10.3390/v14071544 - 15 Jul 2022
Viewed by 1642
Abstract
Classical swine fever can be controlled effectively by vaccination with C-strain vaccine. In this study, we developed a novel competitive enzyme-linked immunosorbent assay (cELISA) based on a C-strain Erns specific monoclonal antibody (mAb 1504), aiming to serologically measure immune responses to C-strain [...] Read more.
Classical swine fever can be controlled effectively by vaccination with C-strain vaccine. In this study, we developed a novel competitive enzyme-linked immunosorbent assay (cELISA) based on a C-strain Erns specific monoclonal antibody (mAb 1504), aiming to serologically measure immune responses to C-strain vaccine in pigs, and finally to make the C-strain become a DIVA-compatible vaccine. The cELISA system was established based on the strategy that mAb 1504 will compete with the C-strain induced antibodies in the pig serum to bind the C-strain Erns protein. The cELISA was optimized and was further evaluated by testing different categories of pig sera. It can efficiently differentiate C-strain immunized from wild-type CSFV-infected pigs and lacks cross-reaction with other common swine viruses and viruses in genus Pestivirus such as Bovine viral diarrhea virus (BVDV). The C-strain antibody can be tested in pigs 7–14 days post vaccination with this cELISA. The sensitivity and specificity of the established cELISA were 100% (95% confidence interval: 95.60 to 100%) and 100% (95% confidence interval: 98.30 to 100%), respectively. This novel cELISA is a reliable tool for specifically measuring and differentiating immune responses to C-strain vaccine in pigs. By combining with the wild-type CSFV-specific infection tests, it can make the C-strain have DIVA capability. Full article
(This article belongs to the Special Issue Pathogenesis of Viral Infections: Implications in the Development of Vaccines and Diagnostic Tools)
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13 pages, 2699 KiB  
Article
Expanding Mouse-Adapted Yamagata-like Influenza B Viruses in Eggs Enhances In Vivo Lethality in BALB/c Mice
by Matthew J. Pekarek, Erika M. Petro-Turnquist, Adam Rubrum, Richard J. Webby and Eric A. Weaver
Viruses 2022, 14(6), 1299; https://0-doi-org.brum.beds.ac.uk/10.3390/v14061299 - 14 Jun 2022
Cited by 2 | Viewed by 2070
Abstract
Despite the yearly global impact of influenza B viruses (IBVs), limited host range has been a hurdle to developing a readily accessible small animal disease model for vaccine studies. Mouse-adapting IBV can produce highly pathogenic viruses through serial lung passaging in mice. Previous [...] Read more.
Despite the yearly global impact of influenza B viruses (IBVs), limited host range has been a hurdle to developing a readily accessible small animal disease model for vaccine studies. Mouse-adapting IBV can produce highly pathogenic viruses through serial lung passaging in mice. Previous studies have highlighted amino acid changes throughout the viral genome correlating with increased pathogenicity, but no consensus mutations have been determined. We aimed to show that growth system can play a role in mouse-adapted IBV lethality. Two Yamagata-lineage IBVs were serially passaged 10 times in mouse lungs before expansion in embryonated eggs or Madin–Darby canine kidney cells (London line) for use in challenge studies. We observed that virus grown in embryonated eggs was significantly more lethal in mice than the same virus grown in cell culture. Ten additional serial lung passages of one strain again showed virus grown in eggs was more lethal than virus grown in cells. Additionally, no mutations in the surface glycoprotein amino acid sequences correlated to differences in lethality. Our results suggest growth system can influence lethality of mouse-adapted IBVs after serial lung passaging. Further research can highlight improved mechanisms for developing animal disease models for IBV vaccine research. Full article
(This article belongs to the Special Issue Pathogenesis of Viral Infections: Implications in the Development of Vaccines and Diagnostic Tools)
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13 pages, 3085 KiB  
Article
Effect of Killed PRRSV Vaccine on Gut Microbiota Diversity in Pigs
by Fangfeng Yuan, Jaishree Sharma, Som G. Nanjappa, Christopher A. Gaulke and Ying Fang
Viruses 2022, 14(5), 1081; https://0-doi-org.brum.beds.ac.uk/10.3390/v14051081 - 18 May 2022
Cited by 3 | Viewed by 2345
Abstract
Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most economically important pathogens affecting the global swine industry. Vaccination is still a main strategy for PRRSV control; however, host factors associated with vaccine efficacy remain poorly understood. Growing evidence suggests that [...] Read more.
Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most economically important pathogens affecting the global swine industry. Vaccination is still a main strategy for PRRSV control; however, host factors associated with vaccine efficacy remain poorly understood. Growing evidence suggests that mucosa-associated microbiomes may play a role in the responses to vaccination. In this study, we investigated the effects of a killed virus vaccine on the gut microbiome diversity in pigs. Fecal microbial communities were longitudinally assessed in three groups of pigs (vaccinated/challenged with PRRSV, unvaccinated/challenged with PRRSV, and unvaccinated/unchallenged) before and after vaccination and after viral challenge. We observed significant interaction effects between viral challenge and vaccination on both taxonomic richness and community diversity of the gut microbiota. While some specific taxonomic alterations appear to be enhanced in vaccinated/challenged pigs, others appeared to be more consistent with the levels in control animals (unvaccinated/unchallenged), indicating that vaccination incompletely protects against viral impacts on the microbiome. The abundances of several microbial taxa were further determined to be correlated with the level of viral load and the amount of PRRSV reactive CD4+ and CD8+ T-cells. This study highlights the potential roles of gut microbiota in the response of pigs to vaccination, which may pave the road for the development of novel strategies to enhance vaccine efficacy. Full article
(This article belongs to the Special Issue Pathogenesis of Viral Infections: Implications in the Development of Vaccines and Diagnostic Tools)
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