PRRSV Vaccinology and Immunology

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Veterinary Vaccines".

Deadline for manuscript submissions: closed (30 June 2021) | Viewed by 75557

Special Issue Editors

Nebraska Center for Virology and Department of Animal Science, University of Nebraska-Lincoln, Lincoln, NE 68583, USA
Interests: PRRSV; influenza; ASFV; vaccine development; viral pathogenesis
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
School of Veterinary and Biomedical Sciences, University of Nebraska–Lincoln, Lincoln, NE, USA
Interests: RNA virus transcription and replication; viral vaccines; antivirals; innate and adaptive immune responses; immunopathogenesis; VSV; PRRSV; Zika Virus; SARS-CoV-2

Special Issue Information

Dear Colleagues,

Almost 30 years have elapsed since the first PRRSV strain was successfully isolated and propagated in cell culture. Much have been learned about the virus biology, pathogenesis, and its interaction with the host. A number of vaccines against PRRSV have been available. Regional efforts to eradicate the virus from the swine herds have been attempted. Despite this significant progress, PRRSV remains one of the most economically important viral pathogens affecting the swine production worldwide.

The scope of this special issue focuses on the recent findings on the efficacy of PRRS vaccines under experimental and production conditions, influence of vaccines on virus transmission and evolution within a swine herd, host immune response to a wild-type virus infection or vaccination, and rationale design of a new generation of vaccines with improved levels of safety and efficacy.

Dr. Hiep L. X. Vu
Prof. Dr. Asit Pattnaik
Guest Editors

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Keywords

  • Vaccine efficacy
  • Vaccine design
  • Heterologous protection
  • Immune response
  • Correlates of protections
  • Immune evasion
  • Viral transmission
  • Viral evolution

Published Papers (19 papers)

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Research

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15 pages, 2665 KiB  
Article
Evaluation of the Cross-Protective Efficacy of a Chimeric PRRSV Vaccine against Two Genetically Diverse PRRSV2 Field Strains in a Reproductive Model
by Chang-Gi Jeong, Amina Khatun, Salik Nazki, Seung-Chai Kim, Yun-Hee Noh, Sang-Chul Kang, Dong-Uk Lee, Myeon-Sik Yang, Nadeem Shabir, In-Joong Yoon, Bumseok Kim and Won-Il Kim
Vaccines 2021, 9(11), 1258; https://doi.org/10.3390/vaccines9111258 - 31 Oct 2021
Cited by 4 | Viewed by 2533
Abstract
Despite the routine use of porcine reproductive and respiratory syndrome (PRRS)-modified live vaccines, serious concerns are currently being raised due to their quick reversion to virulence and limited cross-protection against divergent PRRS virus (PRRSV) strains circulating in the field. Therefore, a PRRS chimeric [...] Read more.
Despite the routine use of porcine reproductive and respiratory syndrome (PRRS)-modified live vaccines, serious concerns are currently being raised due to their quick reversion to virulence and limited cross-protection against divergent PRRS virus (PRRSV) strains circulating in the field. Therefore, a PRRS chimeric vaccine (JB1) was produced using a DNA-launched infectious clone by replacing open reading frames (ORFs) 3–6 with those from a mixture of two genetically different PRRSV2 strains (K07–2273 and K08–1054) and ORF1a with that from a mutation-resistant PRRSV strain (RVRp22) exhibiting an attenuated phenotype. To evaluate the safety and cross-protective efficacy of JB1 in a reproductive model, eight PRRS-negative pregnant sows were purchased and divided into four groups. Four sows in two of the groups were vaccinated with JB1, and the other 4 sows were untreated at gestational day 60. At gestational day 93, one vaccinated group and one nonvaccinated group each were challenged with either K07–2273 or K08–1054. All of the sows aborted or delivered until gestation day 115 (24 days post challenge), and the newborn piglets were observed up to the 28th day after birth, which was the end of the experiment. Overall, pregnant sows of the JB1-vaccinated groups showed no meaningful viremia after vaccination and significant reductions in viremia with K07–2273 and K08–1054, exhibiting significantly higher levels of serum virus-neutralizing antibodies than non-vaccinated sows. Moreover, the JB1-vaccinated groups did not exhibit any abortion due to vaccination and showed improved piglet viability and birth weight. The piglets from JB1-vaccinated sows displayed lower viral concentrations in serum and fewer lung lesions compared with those of the piglets from the nonvaccinated sows. Therefore, JB1 is a safe and effective vaccine candidate that confers simultaneous protection against two genetically different PRRSV strains. Full article
(This article belongs to the Special Issue PRRSV Vaccinology and Immunology)
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12 pages, 1195 KiB  
Article
Impacts of Quarterly Sow Mass Vaccination with a Porcine Reproductive and Respiratory Syndrome Virus Type 1 (PRRSV-1) Modified Live Vaccine in Two Herds
by Kasper Pedersen, Charlotte Sonne Kristensen, Lise Kirstine Kvisgaard and Lars Erik Larsen
Vaccines 2021, 9(10), 1057; https://doi.org/10.3390/vaccines9101057 - 23 Sep 2021
Cited by 3 | Viewed by 2334
Abstract
In recent years, there has been a considerable increase in the use of Modified Live PRRSV Vaccines (MLV) for mass vaccination in Denmark. The potential risks and negative impact of this strategy have been sparsely studied. The aim of this study was to [...] Read more.
In recent years, there has been a considerable increase in the use of Modified Live PRRSV Vaccines (MLV) for mass vaccination in Denmark. The potential risks and negative impact of this strategy have been sparsely studied. The aim of this study was to investigate the impact of quarterly sow mass vaccination in two Danish sow herds. The study was performed as an observational prospective cohort of 120 sows in each of two commercial breeding herds in a paired design. Blood samples were taken from sows and oral fluid samples from nursery pigs (four to ten weeks old) before and after vaccination. The presence of PRRSV-1 RNA was measured by real time quantitative reverse transcription-polymerase chain reaction (RT-qPCR), and the level of PRRSV-1 specific antibodies was measured by two different serological assays. PRRS virus was not detected in the sow herds two days before and two weeks after vaccination, but the vaccine strain virus was detected in the nursery pigs. The prevalence of sows without antibodies towards PRRSV-1 went from 6–15% before vaccination to 1–4% after vaccination depending on the serological assay used, despite the fact that they had previously been repeatedly vaccinated. Four sows tested negative for antibodies in both assays after vaccination. Full article
(This article belongs to the Special Issue PRRSV Vaccinology and Immunology)
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13 pages, 2031 KiB  
Article
Evaluation of Four Commercial Vaccines for the Protection of Piglets against the Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus (hp-PRRSV) QH-08 Strain
by Yaozhong Ding, Ashenafi Kiros Wubshet, Xiaolong Ding, Zhongwang Zhang, Qian Li, Junfei Dai, Qian Hou, Yonghao Hu and Jie Zhang
Vaccines 2021, 9(9), 1020; https://doi.org/10.3390/vaccines9091020 - 14 Sep 2021
Cited by 7 | Viewed by 2676
Abstract
Vaccination is the best way to prevent economic losses from highly pathogenic porcine reproductive and respiratory syndrome virus (hp-PRRSV) disease. However, the commercially available vaccines need to periodically evaluate their efficacy against infections caused by new hp-PRRSV variants. Therefore, the objective of this [...] Read more.
Vaccination is the best way to prevent economic losses from highly pathogenic porcine reproductive and respiratory syndrome virus (hp-PRRSV) disease. However, the commercially available vaccines need to periodically evaluate their efficacy against infections caused by new hp-PRRSV variants. Therefore, the objective of this study was to evaluate the efficacy of four (two modified live vaccines (MLV) and two inactivated) PRRSV commercial vaccines in piglets challenged with QH-08 and to estimate the genetic distance of the vaccine strains from recently isolated (QH-08) filed strain. Randomly, piglets (n = 5) allocated in groups 1–4 were immunized with Ingelvac PRRS MLV, CH-1a, JXA1, and JXA1-RMLV vaccines, whereas the infected and non-infected control piglets in groups 5 and 6 (n = 3), respectively, were subjected to PBS. Results indicated that JXA1 and JXA1-R MLV vaccines showed complete protection, but Ingelvac PRRS MLV and CH-1α vaccines revealed partial protection against the QH-08 PRRSV challenge. Similarly, vaccinated and challenged pigs showed lower macroscopic and microscopic lesions than the pigs in group 5. Our findings demonstrated a new insight that the variation in ORF1a and 1b coding sequence could significantly affect PRRSV vaccines efficacy. In conclusion, QH-08 is a good candidate for the design and development of an innovative PRRSV vaccine that ultimately helps in the control and prevention strategies. Full article
(This article belongs to the Special Issue PRRSV Vaccinology and Immunology)
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20 pages, 3130 KiB  
Article
Recombinant Antigen of Type 2 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV-2) Promotes M1 Repolarization of Porcine Alveolar Macrophages and Th1 Type Response
by Rika Wahyuningtyas, Yin-Siew Lai, Mei-Li Wu, Hsin-Wei Chen, Wen-Bin Chung, Hso-Chi Chaung and Ko-Tung Chang
Vaccines 2021, 9(9), 1009; https://doi.org/10.3390/vaccines9091009 - 10 Sep 2021
Cited by 5 | Viewed by 3104
Abstract
The polarization status of porcine alveolar macrophages (PAMs) determines the infectivity of porcine reproductive and respiratory syndrome virus (PRRSV). PRRSV infection skews macrophage polarization toward an M2 phenotype, followed by T-cells inactivation. CD163, one of the scavenger receptors of M2 macrophages, has been [...] Read more.
The polarization status of porcine alveolar macrophages (PAMs) determines the infectivity of porcine reproductive and respiratory syndrome virus (PRRSV). PRRSV infection skews macrophage polarization toward an M2 phenotype, followed by T-cells inactivation. CD163, one of the scavenger receptors of M2 macrophages, has been described as a putative receptor for PRRSV. In this study, we examined two types of PRRSV-2-derived recombinant antigens, A1 (g6Ld10T) and A2 (lipo-M5Nt), for their ability to mediate PAM polarization and T helper (Th1) response. A1 and A2 were composed of different combination of ORF5, ORF6, and ORF7 in full or partial length. To enhance the adaptive immunity, they were conjugated with T cells epitopes or lipidated elements, respectively. Our results showed that CD163+ expression on PAMs significantly decreased after being challenged with A1 but not A2, followed by a significant increase in pro-inflammatory genes (TNF-α, IL-6, and IL-12). In addition, next generation sequencing (NGS) data show an increase in T-cell receptor signaling in PAMs challenged with A1. Using a co-culture system, PAMs challenged with A1 can induce Th1 activation by boosting IFN-γ and IL-12 secretion and TNF-α expression. In terms of innate and T-cell-mediated immunity, we conclude that A1 is regarded as a potential vaccine for immunization against PRRSV infection due to its ability to reverse the polarization status of PAMs toward pro-inflammatory phenotypes, which in turn reduces CD163 expression for viral entry and increases immunomodulation for Th1-type response. Full article
(This article belongs to the Special Issue PRRSV Vaccinology and Immunology)
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17 pages, 2432 KiB  
Article
Phylogenetic Structure and Sequential Dominance of Sub-Lineages of PRRSV Type-2 Lineage 1 in the United States
by Igor A. D. Paploski, Nakarin Pamornchainavakul, Dennis N. Makau, Albert Rovira, Cesar A. Corzo, Declan C. Schroeder, Maxim C-J. Cheeran, Andrea Doeschl-Wilson, Rowland R. Kao, Samantha Lycett and Kimberly VanderWaal
Vaccines 2021, 9(6), 608; https://doi.org/10.3390/vaccines9060608 - 5 Jun 2021
Cited by 39 | Viewed by 5959
Abstract
The genetic diversity and frequent emergence of novel genetic variants of porcine reproductive and respiratory syndrome virus type-2 (PRRSV) hinders control efforts, yet drivers of macro-evolutionary patterns of PRRSV remain poorly documented. Utilizing a comprehensive database of >20,000 orf5 sequences, our objective was [...] Read more.
The genetic diversity and frequent emergence of novel genetic variants of porcine reproductive and respiratory syndrome virus type-2 (PRRSV) hinders control efforts, yet drivers of macro-evolutionary patterns of PRRSV remain poorly documented. Utilizing a comprehensive database of >20,000 orf5 sequences, our objective was to classify variants according to the phylogenetic structure of PRRSV co-circulating in the U.S., quantify evolutionary dynamics of sub-lineage emergence, and describe potential antigenic differences among sub-lineages. We subdivided the most prevalent lineage (Lineage 1, accounting for approximately 60% of available sequences) into eight sub-lineages. Bayesian coalescent SkyGrid models were used to estimate each sub-lineage’s effective population size over time. We show that a new sub-lineage emerged every 1 to 4 years and that the time between emergence and peak population size was 4.5 years on average (range: 2–8 years). A pattern of sequential dominance of different sub-lineages was identified, with a new dominant sub-lineage replacing its predecessor approximately every 3 years. Consensus amino acid sequences for each sub-lineage differed in key GP5 sites related to host immunity, suggesting that sub-lineage turnover may be linked to immune-mediated competition. This has important implications for understanding drivers of genetic diversity and emergence of new PRRSV variants in the U.S. Full article
(This article belongs to the Special Issue PRRSV Vaccinology and Immunology)
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13 pages, 2623 KiB  
Article
Comparison of Primary Virus Isolation in Pulmonary Alveolar Macrophages and Four Different Continuous Cell Lines for Type 1 and Type 2 Porcine Reproductive and Respiratory Syndrome Virus
by Jiexiong Xie, Nick Vereecke, Sebastiaan Theuns, Dayoung Oh, Nathalie Vanderheijden, Ivan Trus, Jannes Sauer, Philip Vyt, Caroline Bonckaert, Christian Lalonde, Chantale Provost, Carl A. Gagnon and Hans Nauwynck
Vaccines 2021, 9(6), 594; https://doi.org/10.3390/vaccines9060594 - 3 Jun 2021
Cited by 5 | Viewed by 3605
Abstract
Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) has a highly restricted cellular tropism. In vivo, the virus primarily infects tissue-specific macrophages in the nose, lungs, tonsils, and pharyngeal lymphoid tissues. In vitro however, the MARC-145 cell line is one of the few PRRSV [...] Read more.
Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) has a highly restricted cellular tropism. In vivo, the virus primarily infects tissue-specific macrophages in the nose, lungs, tonsils, and pharyngeal lymphoid tissues. In vitro however, the MARC-145 cell line is one of the few PRRSV susceptible cell lines that are routinely used for in vitro propagation. Previously, several PRRSV non-permissive cell lines were shown to become susceptible to PRRSV infection upon expression of recombinant entry receptors (e.g., PK15Sn-CD163, PK15S10-CD163). In the present study, we examined the suitability of different cell lines as a possible replacement of primary pulmonary alveolar macrophages (PAM) cells for isolation and growth of PRRSV. The susceptibility of four different cell lines (PK15Sn-CD163, PK15S10-CD163, MARC-145, and MARC-145Sn) for the primary isolation of PRRSV from PCR positive sera (both PRRSV1 and PRRSV2) was compared with that of PAM. To find possible correlations between the cell tropism and the viral genotype, 54 field samples were sequenced, and amino acid residues potentially associated with the cell tropism were identified. Regarding the virus titers obtained with the five different cell types, PAM gave the highest mean virus titers followed by PK15Sn-CD163, PK15S10-CD163, MARC-145Sn, and MARC-145. The titers in PK15Sn-CD163 and PK15S10-CD163 cells were significantly correlated with virus titers in PAM for both PRRSV1 (p < 0.001) and PRRSV2 (p < 0.001) compared with MARC-145Sn (PRRSV1: p = 0.22 and PRRSV2: p = 0.03) and MARC-145 (PRRSV1: p = 0.04 and PRRSV2: p = 0.12). Further, a possible correlation between cell tropism and viral genotype was assessed using PRRSV whole genome sequences in a Genome-Wide-Association Study (GWAS). The structural protein residues GP2:187L and N:28R within PRRSV2 sequences were associated with their growth in MARC-145. The GP5:78I residue for PRRSV2 and the Nsp11:155F residue for PRRSV1 was linked to a higher replication on PAM. In conclusion, PK15Sn-CD163 and PK15S10-CD163 cells are phenotypically closely related to the in vivo target macrophages and are more suitable for virus isolation and titration than MARC-145/MARC-145Sn cells. The residues of PRRSV proteins that are potentially related with cell tropism will be further investigated in the future. Full article
(This article belongs to the Special Issue PRRSV Vaccinology and Immunology)
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12 pages, 1353 KiB  
Article
Challenge of Naïve and Vaccinated Pigs with a Vaccine-Derived Recombinant Porcine Reproductive and Respiratory Syndrome Virus 1 Strain (Horsens Strain)
by Lise K. Kvisgaard, Lars E. Larsen, Charlotte S. Kristensen, Frédéric Paboeuf, Patricia Renson and Olivier Bourry
Vaccines 2021, 9(5), 417; https://doi.org/10.3390/vaccines9050417 - 22 Apr 2021
Cited by 5 | Viewed by 2902
Abstract
In July 2019, a vaccine-derived recombinant Porcine reproductive and respiratory syndrome virus 1 strain (PRRSV-1) (Horsens strain) infected more than 40 Danish sow herds, resulting in severe losses. In the present study, the pathogenicity of the recombinant Horsens strain was assessed and compared [...] Read more.
In July 2019, a vaccine-derived recombinant Porcine reproductive and respiratory syndrome virus 1 strain (PRRSV-1) (Horsens strain) infected more than 40 Danish sow herds, resulting in severe losses. In the present study, the pathogenicity of the recombinant Horsens strain was assessed and compared to a reference PRRSV-1 strain using a well-characterized experimental model in young SPF pigs. Furthermore, the efficacies of three different PRRSV-1 MLV vaccines to protect pigs against challenge with the recombinant strain were assessed. Following challenge, the unvaccinated pigs challenged with the Horsens strain had significant increased viral load in serum compared to all other groups. No macroscopic changes were observed at necropsy, but tissue from the lungs and tonsils from almost all pigs were PRRSV-positive. The viral load in serum was lower in all vaccinated groups compared to the unvaccinated group challenged with the Horsens strain, and only small differences were seen among the vaccinated groups. The findings in the present study, combined with two other recent reports, indicate that this recombinant “Horsens” strain indeed is capable of inducing infection in growing pigs as well as in pregnant sows that is comparable to or even exceeding those induced by typical PRRSV-1, subtype 1 strains. However, absence of notable clinical signs and lack of significant macroscopic changes indicate that this strain is less virulent than previously characterized highly virulent PRRSV-1 strains. Full article
(This article belongs to the Special Issue PRRSV Vaccinology and Immunology)
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12 pages, 1417 KiB  
Article
Correlation of Neutralizing Antibodies (NAbs) between Sows and Piglets and Evaluation of Protectability Associated with Maternally Derived NAbs in Pigs against Circulating Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) under Field Conditions
by Fu-Chun Hsueh, Sheng-Yuan Wang, Wei-Hao Lin, Chuen-Fu Lin, Chen-Yu Tsai, Chin-Wen Huang, Ning Sun, Ming-Tang Chiou and Chao-Nan Lin
Vaccines 2021, 9(5), 414; https://doi.org/10.3390/vaccines9050414 - 21 Apr 2021
Cited by 7 | Viewed by 2435
Abstract
Porcine reproductive and respiratory syndrome (PRRS), which is caused by a highly transmissible pathogen called porcine reproductive and respiratory syndrome virus (PRRSV), has caused severe problems, including reproductive disorders in sows and respiratory symptoms in nursery pigs worldwide, since the early 1990s. However, [...] Read more.
Porcine reproductive and respiratory syndrome (PRRS), which is caused by a highly transmissible pathogen called porcine reproductive and respiratory syndrome virus (PRRSV), has caused severe problems, including reproductive disorders in sows and respiratory symptoms in nursery pigs worldwide, since the early 1990s. However, currently available PRRSV vaccines do not supply complete immunity to confront the viral infection. Elicitation of PRRSV-specific neutralizing antibodies (NAbs) during the preinfectious period has been deemed to be a feasible strategy to modulate this virus, especially in farms where nursery pigs are seized with PRRSVs. A total of 180 piglets in a farrow-to-finish farm that had a natural outbreak of PRRS were distributed into three groups based on the different PRRSV NAbs levels in their dams. In the present study, piglets that received superior maternal-transferred NAbs showed delayed and relatively slight viral loads in serum and, on the whole, higher survival rates against wild PRRSV infections. A positive correlation of maternal NAbs between sows and their piglets was identified; moreover, high NAbs titers in piglets can last for at least 4 weeks. These results provide updated information to develop an appropriate immune strategy for breeding and for future PRRSV control under field conditions. Full article
(This article belongs to the Special Issue PRRSV Vaccinology and Immunology)
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22 pages, 4883 KiB  
Article
Phenotypic and Genetic Evolutions of a Porcine Reproductive and Respiratory Syndrome Modified Live Vaccine after Limited Passages in Pigs
by Julie Eclercy, Patricia Renson, Edouard Hirchaud, Mathieu Andraud, Véronique Beven, Frédéric Paboeuf, Nicolas Rose, Yannick Blanchard and Olivier Bourry
Vaccines 2021, 9(4), 392; https://doi.org/10.3390/vaccines9040392 - 16 Apr 2021
Cited by 5 | Viewed by 2809
Abstract
Modified live vaccines (MLVs) against the porcine reproductive and respiratory syndrome virus (PRRSV) have been regularly associated with safety issues, such as reversion to virulence. In order to characterize the phenotypic and genetic evolution of the PRRSV-1 DV strain from the Porcilis® [...] Read more.
Modified live vaccines (MLVs) against the porcine reproductive and respiratory syndrome virus (PRRSV) have been regularly associated with safety issues, such as reversion to virulence. In order to characterize the phenotypic and genetic evolution of the PRRSV-1 DV strain from the Porcilis® PRRS MLV after limited passages in pigs, three in vivo experiments were performed. Trial#1 aimed (i) at studying transmission of the vaccine strain from vaccinated to unvaccinated contact pigs. Trial#2 and Trial#3 were designed (ii) to assess the reproducibility of Trial#1, using another vaccine batch, and (iii) to compare the virulence levels of two DV strains isolated from vaccinated (passage one) and diseased contact pigs (passage two) from Trial#1. DV strain isolates from vaccinated and contact pigs from Trial#1 and Trial#2 were submitted to Next-Generation Sequencing (NGS) full-genome sequencing. All contact animals from Trial#1 were infected and showed significantly increased viremia compared to vaccinated pigs, whereas no such change was observed during Trial#2. In Trial#3, viremia and transmission were higher for inoculated pigs with passage two of the DV strain, compared with passage one. In this study, we showed that the re-adaptation of the DV strain to pigs is associated with faster replication and increased transmission of the vaccine strain. Punctually, a decrease of attenuation of the DV vaccine strain associated with clinical signs and increased viremia may occur after limited passages in pigs. Furthermore, we identified three mutations linked to pig re-adaptation and five other mutations as potential virulence determinants. Full article
(This article belongs to the Special Issue PRRSV Vaccinology and Immunology)
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16 pages, 3218 KiB  
Article
Concomitant Swine Influenza A Virus Infection Alters PRRSV1 MLV Viremia in Piglets but Does Not Interfere with Vaccine Protection in Experimental Conditions
by Patricia Renson, Céline Deblanc, Juliette Bougon, Mireille Le Dimna, Stéphane Gorin, Sophie Mahé, Nicolas Barbier, Frédéric Paboeuf, Gaëlle Simon and Olivier Bourry
Vaccines 2021, 9(4), 356; https://doi.org/10.3390/vaccines9040356 - 7 Apr 2021
Cited by 8 | Viewed by 2476
Abstract
Modified-live vaccines (MLVs) against porcine reproductive and respiratory syndrome viruses (PRRSVs) are usually administrated to piglets at weaning when swine influenza A virus (swIAV) infections frequently occur. SwIAV infection induces a strong interferon alpha (IFNa) response and IFNa was shown to abrogate PRRSV2 [...] Read more.
Modified-live vaccines (MLVs) against porcine reproductive and respiratory syndrome viruses (PRRSVs) are usually administrated to piglets at weaning when swine influenza A virus (swIAV) infections frequently occur. SwIAV infection induces a strong interferon alpha (IFNa) response and IFNa was shown to abrogate PRRSV2 MLV replication and an inherent immune response. In this study, we evaluated the impacts of swIAV infection on the replication of a PRRSV1 MLV (MLV1), post-vaccine immune responses and post-challenge vaccine efficacy at both the systemic and pulmonary levels. Piglets were either swIAV inoculated and MLV1 vaccinated 6 h apart or singly vaccinated or mock inoculated and mock vaccinated. Four weeks after vaccination, the piglets were challenged with a PRRSV1 field strain. The results showed that swIAV infection delayed MLV1 viremia by six days and post-vaccine seroconversion by four days. After the PRRSV1 challenge, the swIAV enhanced the PRRSV1-specific cell-mediated immunity (CMI) but the PRRSV1 field strain viremia was not better controlled. High IFNa levels that were detected early after swIAV infection could have been responsible for both the inhibition of MLV1 replication and CMI enhancement. Thus, whereas swIAV infection had a negative impact on humoral responses post-vaccination, it did not interfere with the protective effectiveness of the PRRSV MLV1 in our experimental conditions. Full article
(This article belongs to the Special Issue PRRSV Vaccinology and Immunology)
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19 pages, 4692 KiB  
Article
Maternal Autogenous Inactivated Virus Vaccination Boosts Immunity to PRRSV in Piglets
by Andrew R. Kick, Zoe C. Wolfe, Amanda F. Amaral, Lizette M. Cortes, Glen W. Almond, Elisa Crisci, Phillip C. Gauger, Jeremy Pittman and Tobias Käser
Vaccines 2021, 9(2), 106; https://doi.org/10.3390/vaccines9020106 - 31 Jan 2021
Cited by 11 | Viewed by 4362
Abstract
Maternal-derived immunity is a critical component for the survival and success of offspring in pigs to protect from circulating pathogens such as Type 2 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV-2). The purpose of this study is to investigate the transfer of anti-PRRSV [...] Read more.
Maternal-derived immunity is a critical component for the survival and success of offspring in pigs to protect from circulating pathogens such as Type 2 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV-2). The purpose of this study is to investigate the transfer of anti-PRRSV immunity to piglets from gilts that received modified-live virus (MLV) alone (treatment (TRT) 0), or in combination with one of two autogenous inactivated vaccines (AIVs, TRT 1+2). Piglets from these gilts were challenged with the autogenous PRRSV-2 strain at two weeks of age and their adaptive immune response (IR) was evaluated until 4 weeks post inoculation (wpi). The systemic humoral and cellular IR was analyzed in the pre-farrow gilts, and in piglets, pre-inoculation, and at 2 and 4 wpi. Both AIVs partially protected the piglets with reduced lung pathology and increased weight gain; TRT 1 also lowered piglet viremia, best explained by the AIV-induced production of neutralizing antibodies in gilts and their transfer to the piglets. In piglets, pre-inoculation, the main systemic IFN-γ producers were CD21α+ B cells. From 0 to 4 wpi, the role of these B cells declined and CD4 T cells became the primary systemic IFN-γ producers. In the lungs, CD8 T cells were the primary and CD4 T cells were the secondary IFN-γ producers, including a novel subset of porcine CD8αCCR7 CD4 T cells, potentially terminally differentiated CD4 TEMRA cells. In summary, this study demonstrates that maternal AIV vaccination can improve protection of pre-weaning piglets against PRRSV-2; it shows the importance of transferring neutralizing antibodies to piglets, and it introduces two novel immune cell subsets in pigs—IFN-γ producing CD21α+ B cells and CD8αCCR7 CD4 T cells. Full article
(This article belongs to the Special Issue PRRSV Vaccinology and Immunology)
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16 pages, 7070 KiB  
Article
CD163 Antibodies Inhibit PRRSV Infection via Receptor Blocking and Transcription Suppression
by Huiling Xu, Zehui Liu, Suya Zheng, Guangwei Han and Fang He
Vaccines 2020, 8(4), 592; https://doi.org/10.3390/vaccines8040592 - 9 Oct 2020
Cited by 7 | Viewed by 3497
Abstract
CD163 has been identified as the essential receptor for Porcine reproductive and respiratory syndrome (PRRSV), a major etiologic agent of pigs. Scavenger receptor cysteine-rich domain 5–9 (SRCR5–9) in CD163 was shown to be responsible for the virus interaction. In this study, monoclonal antibodies [...] Read more.
CD163 has been identified as the essential receptor for Porcine reproductive and respiratory syndrome (PRRSV), a major etiologic agent of pigs. Scavenger receptor cysteine-rich domain 5–9 (SRCR5–9) in CD163 was shown to be responsible for the virus interaction. In this study, monoclonal antibodies (mAbs) 6E8 and 9A10 against SRCR5–9 were selected based on the significant activity to inhibit PRRSV infection in Porcine Alveolar Macrophage (PAMs) and Marc-145. Both mAbs are capable of blocking variable PRRSV strains in a dose-dependent manner. Meanwhile, as candidates for both prevention and therapeutics, the antibodies successfully inhibit PRRSV infection and the related NF-κB pathway either before or after virus attachment. Besides, the antibody treatment with either mAb leads to a remarkable decrease of CD163 transcription in PAMs and Marc-145. It is potentially caused by the excessive accumulation of membrane associated CD163 due to the failure in CD163 cleavage with the antibody binding. Further, conformational epitopes targeted by 6E8 and 9A10 are identified to be spanning residues 570SXDVGXV576 in SRCR5 and Q797 in SRCR7, respectively. CD163 with mutated epitopes expressed in 3D4 cells fails to support PRRSV infection while wild type CD163 recovers PRRSV infection, indicating the critical role of these residues in PRRSV invasion. These findings promote the understanding in the interaction between PRRSV and the receptor and provide novel broad antiviral strategies for PRRSV prevention and treatment via alternative mechanisms. Full article
(This article belongs to the Special Issue PRRSV Vaccinology and Immunology)
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15 pages, 1122 KiB  
Article
Evaluation of Antibody Response Directed against Porcine Reproductive and Respiratory Syndrome Virus Structural Proteins
by Hung Q. Luong, Huong T. L. Lai and Hiep L. X. Vu
Vaccines 2020, 8(3), 533; https://doi.org/10.3390/vaccines8030533 - 16 Sep 2020
Cited by 8 | Viewed by 4156
Abstract
Luciferase-immunoprecipitation system (LIPS), a liquid phase immunoassay, was used to evaluate antibody responses directed against the structural proteins of PRRSV in pigs that were experimentally infected with virulent PRRSV strains. First, the viral N protein was used as a model antigen to validate [...] Read more.
Luciferase-immunoprecipitation system (LIPS), a liquid phase immunoassay, was used to evaluate antibody responses directed against the structural proteins of PRRSV in pigs that were experimentally infected with virulent PRRSV strains. First, the viral N protein was used as a model antigen to validate the assay. The LIPS results were highly comparable to that of the commercial IDEXX PRRS X3 ELISA. Subsequently, the assay was applied to simultaneously measure antibody reactivity against all eight structural proteins of PRRSV. The highest immunoreactivities were detected against GP3, M, and N proteins while the lowest reactivity was detected against ORF5a protein. Comparative analysis of the kinetics of antibody appearance revealed that antibodies specific to N protein appeared earlier than antibodies against GP3. Finally, the assay was applied to measure immunoreactivities of clinical serum samples against N and GP3. The diagnostic sensitivity of the LIPS with N protein was superior to that of the LIPS with GP3. Collectively, the results provide additional information about the host antibody response to PRRSV infection. Full article
(This article belongs to the Special Issue PRRSV Vaccinology and Immunology)
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22 pages, 4482 KiB  
Article
Porcine Reproductive and Respiratory Syndrome Virus Interferes with Swine Influenza A Virus Infection of Epithelial Cells
by Georges Saade, Déborah Ménard, Caroline Hervet, Patricia Renson, Erika Hue, Jianzhong Zhu, Laurence Dubreil, Romain Paillot, Stéphane Pronost, Olivier Bourry, Gaëlle Simon, Joëlle Dupont, Nicolas Bertho and François Meurens
Vaccines 2020, 8(3), 508; https://doi.org/10.3390/vaccines8030508 - 5 Sep 2020
Cited by 13 | Viewed by 3699
Abstract
Respiratory infections are still a major concern in pigs. Amongst the involved viruses, the porcine reproductive and respiratory syndrome virus (PRRSV) and the swine influenza type A virus (swIAV) have a major impact. These viruses frequently encounter and dual infections are reported. We [...] Read more.
Respiratory infections are still a major concern in pigs. Amongst the involved viruses, the porcine reproductive and respiratory syndrome virus (PRRSV) and the swine influenza type A virus (swIAV) have a major impact. These viruses frequently encounter and dual infections are reported. We analyzed here the molecular interactions between viruses and porcine tracheal epithelial cells as well as lung tissue. PRRSV-1 species do not infect porcine respiratory epithelial cells. However, PRRSV-1, when inoculated simultaneously or shortly before swIAV, was able to inhibit swIAV H1N2 infection, modulate the interferon response and alter signaling protein phosphorylations (ERK, AKT, AMPK, and JAK2), in our conditions. SwIAV inhibition was also observed, although at a lower level, by inactivated PRRSV-1, whereas acid wash treatment inactivating non-penetrated viruses suppressed the interference effect. PRRSV-1 and swIAV may interact at several stages, before their attachment to the cells, when they attach to their receptors, and later on. In conclusion, we showed for the first time that PRRSV can alter the relation between swIAV and its main target cells, opening the doors to further studies on the interplay between viruses. Consequences of these peculiar interactions on viral infections and vaccinations using modified live vaccines require further investigations. Full article
(This article belongs to the Special Issue PRRSV Vaccinology and Immunology)
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Review

Jump to: Research

20 pages, 1721 KiB  
Review
Porcine Reproductive and Respiratory Syndrome Virus: Immune Escape and Application of Reverse Genetics in Attenuated Live Vaccine Development
by Honglei Wang, Yangyang Xu and Wenhai Feng
Vaccines 2021, 9(5), 480; https://doi.org/10.3390/vaccines9050480 - 10 May 2021
Cited by 17 | Viewed by 3955
Abstract
Porcine reproductive and respiratory syndrome virus (PRRSV), an RNA virus widely prevalent in pigs, results in significant economic losses worldwide. PRRSV can escape from the host immune response in several processes. Vaccines, including modified live vaccines and inactivated vaccines, are the best available [...] Read more.
Porcine reproductive and respiratory syndrome virus (PRRSV), an RNA virus widely prevalent in pigs, results in significant economic losses worldwide. PRRSV can escape from the host immune response in several processes. Vaccines, including modified live vaccines and inactivated vaccines, are the best available countermeasures against PRRSV infection. However, challenges still exist as the vaccines are not able to induce broad protection. The reason lies in several facts, mainly the variability of PRRSV and the complexity of the interaction between PRRSV and host immune responses, and overcoming these obstacles will require more exploration. Many novel strategies have been proposed to construct more effective vaccines against this evolving and smart virus. In this review, we will describe the mechanisms of how PRRSV induces weak and delayed immune responses, the current vaccines of PRRSV, and the strategies to develop modified live vaccines using reverse genetics systems. Full article
(This article belongs to the Special Issue PRRSV Vaccinology and Immunology)
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16 pages, 1117 KiB  
Review
The Function of the PRRSV–Host Interactions and Their Effects on Viral Replication and Propagation in Antiviral Strategies
by Jun Ma, Lulu Ma, Meiting Yang, Wei Wu, Wenhai Feng and Zhongzhou Chen
Vaccines 2021, 9(4), 364; https://doi.org/10.3390/vaccines9040364 - 9 Apr 2021
Cited by 24 | Viewed by 5368
Abstract
Porcine reproductive and respiratory syndrome virus (PRRSV) affects the global swine industry and causes disastrous economic losses each year. The genome of PRRSV is an enveloped single-stranded positive-sense RNA of approximately 15 kb. The PRRSV replicates primarily in alveolar macrophages of pig lungs [...] Read more.
Porcine reproductive and respiratory syndrome virus (PRRSV) affects the global swine industry and causes disastrous economic losses each year. The genome of PRRSV is an enveloped single-stranded positive-sense RNA of approximately 15 kb. The PRRSV replicates primarily in alveolar macrophages of pig lungs and lymphatic organs and causes reproductive problems in sows and respiratory symptoms in piglets. To date, studies on how PRRSV survives in the host, the host immune response against viral infections, and pathogenesis, have been reported. PRRSV vaccines have been developed, including inactive virus, modified live virus, attenuated live vaccine, DNA vaccine, and immune adjuvant vaccines. However, there are certain problems with the durability and effectiveness of the licensed vaccines. Moreover, the high variability and fast-evolving populations of this RNA virus challenge the design of PRRSV vaccines, and thus effective vaccines against PRRSV have not been developed successfully. As is well known, viruses interact with the host to escape the host’s immune response and then replicate and propagate in the host, which is the key to virus survival. Here, we review the complex network and the mechanism of PRRSV–host interactions in the processes of virus infection. It is critical to develop novel antiviral strategies against PRRSV by studying these host–virus interactions and structures to better understand the molecular mechanisms of PRRSV immune escape. Full article
(This article belongs to the Special Issue PRRSV Vaccinology and Immunology)
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20 pages, 378 KiB  
Review
Porcine Reproductive and Respiratory Syndrome Modified Live Virus Vaccine: A “Leaky” Vaccine with Debatable Efficacy and Safety
by Lei Zhou, Xinna Ge and Hanchun Yang
Vaccines 2021, 9(4), 362; https://doi.org/10.3390/vaccines9040362 - 9 Apr 2021
Cited by 48 | Viewed by 6243
Abstract
Porcine reproductive and respiratory syndrome (PRRS) caused by the PRRS virus (PRRSV) is one of the most economically important diseases, that has significantly impacted the global pork industry for over three decades, since it was first recognized in the United States in the [...] Read more.
Porcine reproductive and respiratory syndrome (PRRS) caused by the PRRS virus (PRRSV) is one of the most economically important diseases, that has significantly impacted the global pork industry for over three decades, since it was first recognized in the United States in the late 1980s. Attributed to the PRRSV extensive genetic and antigenic variation and rapid mutability and evolution, nearly worldwide epidemics have been sustained by a set of emerging and re-emerging virus strains. Since the first modified live virus (MLV) vaccine was commercially available, it has been widely used for more than 20 years, for preventing and controlling PRRS. On the one hand, MLV can induce a protective immune response against homologous viruses by lightening the clinical signs of pigs and reducing the virus transmission in the affected herd, as well as helping to cost-effectively increase the production performance on pig farms affected by heterologous viruses. On the other hand, MLV can still replicate in the host, inducing viremia and virus shedding, and it fails to confer sterilizing immunity against PRRSV infection, that may accelerate viral mutation or recombination to adapt the host and to escape from the immune response, raising the risk of reversion to virulence. The unsatisfied heterologous cross-protection and safety issue of MLV are two debatable characterizations, which raise the concerns that whether it is necessary or valuable to use this leaky vaccine to protect the field viruses with a high probability of being heterologous. To provide better insights into the immune protection and safety related to MLV, recent advances and opinions on PRRSV attenuation, protection efficacy, immunosuppression, recombination, and reversion to virulence are reviewed here, hoping to give a more comprehensive recognition on MLV and to motivate scientific inspiration on novel strategies and approaches of developing the next generation of PRRS vaccine. Full article
(This article belongs to the Special Issue PRRSV Vaccinology and Immunology)
15 pages, 799 KiB  
Review
Recent Advances in PRRS Virus Receptors and the Targeting of Receptor–Ligand for Control
by Chia-Ming Su, Raymond Robert Richard Rowland and Dongwan Yoo
Vaccines 2021, 9(4), 354; https://doi.org/10.3390/vaccines9040354 - 7 Apr 2021
Cited by 20 | Viewed by 5248
Abstract
Cellular receptors play a critical role in viral infection. At least seven cellular molecules have been identified as putative viral entry mediators for porcine reproductive and respiratory syndrome virus (PRRSV). Accumulating data indicate that among these candidates, CD163, a cysteine-rich scavenger receptor on [...] Read more.
Cellular receptors play a critical role in viral infection. At least seven cellular molecules have been identified as putative viral entry mediators for porcine reproductive and respiratory syndrome virus (PRRSV). Accumulating data indicate that among these candidates, CD163, a cysteine-rich scavenger receptor on macrophages, is the major receptor for PRRSV. This review discusses the recent advances and understanding of the entry of PRRSV into cells, viral pathogenesis in CD163 gene-edited swine, and CD163 as a potential target of receptor–ligand for the control of PRRS. Full article
(This article belongs to the Special Issue PRRSV Vaccinology and Immunology)
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16 pages, 639 KiB  
Review
Commercial PRRS Modified-Live Virus Vaccines
by Chanhee Chae
Vaccines 2021, 9(2), 185; https://doi.org/10.3390/vaccines9020185 - 22 Feb 2021
Cited by 56 | Viewed by 5702
Abstract
Porcine reproductive and respiratory syndrome (PRRS) virus (PRRSV) presents one of the challenging viral pathogens in the global pork industry. PRRS is characterized by two distinct clinical presentations; reproductive failure in breeding animals (gilts, sows, and boars), and respiratory disease in growing pigs. [...] Read more.
Porcine reproductive and respiratory syndrome (PRRS) virus (PRRSV) presents one of the challenging viral pathogens in the global pork industry. PRRS is characterized by two distinct clinical presentations; reproductive failure in breeding animals (gilts, sows, and boars), and respiratory disease in growing pigs. PRRSV is further divided into two species: PRRSV-1 (formerly known as the European genotype 1) and PRRSV-2 (formerly known as the North American genotype 2). A PRRSV-2 modified-live virus (MLV) vaccine was first introduced in North America in 1994, and, six years later, a PRRSV-1 MLV vaccine was also introduced in Europe. Since then, MLV vaccination is the principal strategy used to control PRRSV infection. Despite the fact that MLV vaccines have shown some efficacy, they were problematic as the efficacy of vaccine was often unpredictable and depended highly on the field virus. This paper focused on the efficacy of commercially available MLV vaccines at a global level based on respiratory disease in growing pigs, and maternal and paternal reproductive failure in breeding animals. Full article
(This article belongs to the Special Issue PRRSV Vaccinology and Immunology)
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