Porcine Reproductive and Respiratory Syndrome: History
View Latest Version
Please note this is an old version of this entry, which may differ significantly from the current revision.
Subjects: Infectious Diseases
Contributor:
Lei Zhou

Porcine reproductive and respiratory syndrome (PRRS), characterized as reproductive failure in breeding pigs and respiratory distress in pigs of all age, is one of the costliest diseases disturbing the global swine industry.

  • porcine reproductive and respiratory syndrome virus (PRRSV)
  • modified live virus (MLV) vaccine
  • attenuation
  • heterologous cross-protection
  • safety
  • reversion to virulence
  • recombination

1. Introduction

Porcine reproductive and respiratory syndrome (PRRS), characterized as reproductive failure in breeding pigs and respiratory distress in pigs of all age, is one of the costliest diseases disturbing the global swine industry [1][2]. It was initially reported as a “mystery” disease in the United States in the late 1980s and then outbreaks with similar clinical symptoms were also documented in Western European countries in 1991 [3][4]. Each type of PRRS virus (PRRSV), the causative agent, spread rapidly in its respective continent and eventually widely transmit to the most pig producing countries [2][5]. Subsequently, many virulent strains, quite distinct from early prototype strains, have been continually identified in the United States, China, and Eastern European counties [2][6][7]. Especially in 2006, an unparalleled, large-scale, atypical PRRS outbreak caused by the highly pathogenic variants was documented in China, later in Vietnam, and other Southeast Asian countries [8][9][10]. This event has reformed the concept of pathogenicity and the economic impact of PRRSV. Nowadays, PRRSV remains ongoing through the swine population globally [11].

PRRSV is an enveloped, single-stranded positive-sense RNA (+ssRNA) virus, belonging to the family Arteriviridae, genus Porartevirus [12][13]. There are two species PRRSV-1 (type 1) and PRRSV-2 (type 2), which only share approximately 60% nucleotide sequence identity, and they are recently classified as Betaarterivirus suid 1 and Betaarterivirus suid 2, respectively, in the genus Betaarterivirus (EC 51, Berlin, Germany) (https://talk.ictvonline.org/taxonomy/p/taxonomy-history?taxnode_id=20171832, accessed on 1 July 2019) [14][15][16]. Based on the phylogenic analysis of the ORF5 gene, PRRSV can be divided into at least nine distinct genetic lineages within type 2 virus, and 3 subtypes within type 1 virus [17][18]. A nearly worldwide epidemic has been sustained by a set of emerging and re-emerging strains, attributed to its high-frequency mutation (reported evolutionary rate of 4.7–9.8 × 10−2/site/year) and recombination [19][20][21]. As PRRSV continues to rapidly spread in pig-raising regions worldwide, and its prevalence in the herds remains high, PRRS prevention and control are still the top priorities for pig farms.

Since the first animal vaccination was documented in the year 1872, the vaccine has been widely used for preventing and controlling infectious disease in livestock [22]. As one of the main tools to improve animal health and to reduce/limit pathogens transmission, the vaccine is desired to increase the production of livestock in a cost-effective manner. In addition, vaccinations are also considered to play important roles in reducing antimicrobial use and avoiding the emergence of antimicrobial resistance, as well as improving animal welfares [23]. A modified live virus (MLV) vaccine, the first commercial PRRS vaccine, was launched in the United States in 1994 [24]. Then, the PRRS MLV vaccine has been widely used for almost three decades (Table 1), and it is the major commercial vaccine that can successfully induce a protective immune response against the homologous virus and help in reducing the clinical sign and virus shedding during the heterologous viruses infection. However, it fails to confer sterilizing immunity against various field viruses and cannot provide solid protection against heterologous field strains [1][11][24][25]. Since the PRRS MLV is a leaky vaccine that can prevent the development of disease symptoms, but do not protect against infection and the onwards transmission of pathogens. As well, as in the field virus, MLV can still replicate in a subset of monocyte-derived cells of the host and modulate the immune response, as well, it has the potential issues of reversion to virulence and recombination with field strains, its safety has significantly been concerned [26][27]. Considering that the development and commercialization process of a novel PRRS vaccine cannot always match the speed of mutation and recombination in field strains, the chance for a commercial vaccine to provide homologous protection is limited. Thus, in the field of veterinary practices and pig producers, there are some debates regarding if it is valuable or necessary to use the PRRS MLV, given its leaky characterization [28]. To provide insights on vaccination efforts and the safety of PRRS MLV, the recent advances and opinions on MLV attenuation, protection efficacy, and safety concerns, as well as next-generation vaccine design are reviewed here.

Table 1. Commercially available porcine reproductive and respiratory syndrome (PRRS) modified live virus (MLV) vaccines.

Vaccine

Parental Strain

Species/Type

Lineage

Producer/Developer

Ingelvac PRRSFLEX® EU

94881

PRRSV-1

lineage 1

Boehringer Ingelheim

ReproCyc® PRRS EU

94881

PRRSV-1

lineage 1

Boehringer Ingelheim

Pyrsvac-183®

All-183

PRRSV-1

-

Syva

Unistrain® PRRS

VP-046 BIS

PRRSV-1

lineage 1

Hipra

Amervac® PRRS

VP-046

PRRSV-1

lineage 1

Hipra

Porcilis® PRRS

DV

PRRSV-1

lineage 1

MSD Animal Health

Suvaxyn® PRRS MLV

96V198

PRRSV-1

lineage 1

Zoetis

Prevacent® PRRS

RFLP 184

PRRSV-2

lineage 1

Elanco

Ingelvac PRRS® MLV

VR-2332

PRRSV-2

lineage 5

Boehringer Ingelheim

R98

R98

PRRSV-2

lineage 5

Nanjing Agricultural University

PRIME PAC® PRRS+

Neb-1

PRRSV-2

lineage 7

MSD Animal Health

Ingelvac PRRS® ATP

JA-142

PRRSV-2

lineage 8

Boehringer Ingelheim

JXA1-R

JXA1

PRRSV-2

lineage 8

Chinese Center for Animal Disease Control and Prevention

GDr180

GD

PRRSV-2

lineage 8

China Institute of Veterinary Drug Control

CH-1R

CH-1a

PRRSV-2

lineage 8

Harbin Veterinary Research Institute, CAAS

HuN4-F112

HuN4

PRRSV-2

lineage 8

Harbin Veterinary Research Institute, CAAS

TJM-F92

TJ

PRRSV-2

lineage 8

Institute of Special Animal and Plant Sciences, CAAS

Fostera® PRRS

P129

PRRSV-2

lineage 8

Zoetis

PRRSV-PC

PC *

PRRSV-2

lineage 8

China National Pharmaceutical Group

Note: * A chimeric virus between the classical malicious PTK strain of PRRSV and HP-PRRSV strain, constructed by reverse genetic operation.

2. Protection Efficacy of PRRS MLV

2.1. Protective Mechanism

PRRSV infects a subset of monocyte-derived cells with CD163 expression, such as primary pulmonary alveolar macrophages (PAMs) and pulmonary intravascular macrophages (PIMs), where the virus replication can cause dysfunction or even cell death by necrosis and apoptosis [29]. Meanwhile, PRRSV markedly suppresses the innate immune response and induces inflammatory injury by a variety of mechanisms. As well, PRRSV can cross the maternal-fetal interface (MFI) in the pregnant sow to infect fetuses, leading to reproductive failures [30]. Attenuated PRRSVs infect pigs and cause milder illnesses compared with the virulent wild-type counterparts from which they are derived. Meanwhile, they amplify the amount of antigen available for inducing an immune response in pigs. Since the replication of PRRS MLV mimics that of wild-type virus, the host immune response resembles what occurs after a viral natural infection. However, this is not observed in either inactivated or subunit vaccines [31].

Generally, vaccine-elicited protection relies on the vaccine-induced memory B and T cells. During the PRRSV infection, memory B cells against viral structural and nonstructural proteins are confirmed to be present before viremia is cleared [32]. Even though memory B cells appear to be quite abundant, it has been regarded that there was no anamnestic response to the viral challenge [33]. In the previous studies, almost all challenges were performed before the initial infection of MLV has been completely resolved. In these cases, the protective effect could be due to an ongoing immunity response from the first exposure, before the sterilizing immunity is established. Recently, Rahe et al. created a PRRSV nsp7-specific B cell tetramer to facilitate the detection of PRRSV-specific memory B cells in the lymphoid tissues through a long-term vaccination-challenge study and found that the PRRSV-specific memory B cell response is long-lived in the blood after vaccination and they can be boosted during a live virus re-exposure [34][35][36]. However, it is still too early to conclude whether protection is entirely dependent on PRRSV-specific memory lymphocytes or not.

For many cases of the virus, neutralizing antibodies (NAs) play a key role in protecting from viral infections [37][38][39]. However, for PRRSV, the protection from antibody-mediated neutralization is not very clear, due to the conflicting data from various studies. In the years just after PRRSV identification, the antibodies against PRRSV were initially thought of as an ineffective component of the PRRSV-protective immune response or even deleterious due to the antibody-dependent enhancement (ADE) concerns [40][41]. Generally, the PRRSV NAs in primary infection mainly appear at 28 or 35 day post-infection (dpi), when viremia has been already resolved. Several monoclonal antibodies (mAbs) targeting antigenic regions corresponding to the putative “major NA epitope” have been found to possess less activity [42]. Moreover, it has been demonstrated that M-GP5 ectodomain-specific antibodies purified from the PRRSV-neutralizing serum could bind to the virus but had no neutralization capability, suggesting that the antibodies binding to ectodomain alone are not sufficient to ensure a complete neutralization of PRRSV [43]. In addition, GP3 but not GP5 and M, is regarded as the major target of NA from sera of PRRSV-1 Lelystad virus infected-pigs [44]. This might be reasonable, as GP2, GP3, and GP4 have been confirmed to form a multi-protein complex that binds to the key receptor CD163, playing an important role in PRRSV infectivity [45][46][47]. In addition, once PRRSV ends its first-round infection into the cells, it can utilize nanotubes and exosomes for intercellular spread, resisting to antibody neutralization [48][49]. One more concern is about the NA testing process. Usually, NA titers of most sera are tested on MARC-145 cells, which is not the real host target cell. Our recent study has found that sera with a high NA titer even around 1:96, tested on MARC-145 cells, cannot completely block the PRRSV infectivity in any dilution when parallelly tested on PAMs [50]. This further indicates that the serum with NA titer tested on MARC-145 cells, might not be guaranteed to have the same level of neutralization capability in vivo. In contrast, some other studies have reported that the passive transfer of homologous neutralizing antibodies was shown to prevent reproductive failure and viral transmission to neonatal piglets [51]. In addition, NA titer has been considered as the best predictor of level and duration of viremia [52]. Meanwhile, high titers of broadly neutralizing activity in naturally infected pigs can provide cross-protection against heterologous PRRSV, which correlated with the clearance of the virus from the circulation and tissues [53][54][55]. Thus, the NAs might help reduce PRRSV infection, but cannot completely block the infection, implying that PRRSV might use some strategies to antagonize and escape it. Future studies are still needed to explore the possible mechanism.

Cell-mediated immunity (CMI) and innate immunity are believed to be the major protective mechanism against PRRSV infection [56][57][58][59][60][61]. However, cellular immune response in PRRSV-infected pigs is still poorly understood due to the difficulty of expanding antigen-specific T-cell populations in vitro and the deficiency of tools and reagents to examine antigen-specific responses in vitro or in vivo. Most evaluation on the CMI response was only based on interferon-γ (IFN-γ) ELISPOT or qPCR to test the level of IFN-γ after using PRRSV to stimulate the PBMCs, which were collected from the vaccinated pigs. However, the significance is uncertain, as the specific source of IFN-γ is difficult to further identify. The innate immune response to a PRRSV-1 vaccine (Porcilis® PRRS, MSD) in the first 72 h post-vaccination (hpv) has been investigated through comparing of the PBMC transcriptome profiles at 6, 24, and 72 hpv, between vaccinated and unvaccinated pigs. The results showed that the MAP kinase activity, TRIF-dependent toll-like receptor signaling pathway, T-cell differentiation, and apoptosis were positively regulated, meanwhile, JAK-STAT pathway and regulation, TRAF6-mediated induction of NF-kB and MAPK, the NLRP3 inflammasome, endocytosis, and interferon signaling were downregulated during the early stage of PRRSV vaccination [62][63]. However, the detailed “cross-talk” among infected macrophages and B/T cells, related to the activation of the humoral and cellular immunity, has not been well investigated yet. Thus, the basic research on the mechanism of immune protection is the prerequisite for further improving the cross-protection efficacy of the PRRS MLV vaccine, especially against the heterologous strains.

Pigs are susceptible to PRRSV by direct or indirect exposure, via intranasal, oral, intrauterine, vaginal, and intramuscular routes [64][65]. Once an outbreak occurs, PRRSV tends to circulate within pig herds indefinitely. PRRSV-persistent pigs and the continually induced-susceptible animals can drive endemicity. Vaccination is usually considered as a relatively safer route to reach “herd immunity” [66]. To evaluate vaccine-afforded protection, vaccine trials routinely assess the efficacy at the individual level through immunological, virological, and pathological parameters. For an individual pig, the main objective of vaccination is to protect the animal from the infection and to lessen the clinical symptoms, thereby improving the health level of vaccinated pigs. While at the population level, the efficacy cannot be only evaluated in virological terms [67]. In epidemiological terms, the goal of vaccination is to decrease or even stop viral transmission within a swine farm and reduce infection-related economic losses [64][68][69]. On one side, the PRRS MLV vaccination can reduce the susceptibility of injected pigs, and on the other side, it also decreases the contagiousness of the individuals, by shortening the shedding period and reducing the viral load. Even the heterologous vaccination can decrease the duration of viremia and viral load, resulting in the reduced viral shedding. Several studies have assessed the R0 value of PRRSV transmission in the vaccinated and naïve pigs in the vaccination-challenge trials. For example, in two early studies, PRRSV-1 MLV vaccination could significantly reduce the R0 value (2.78 to 0.53 and 5.42 to 0.30, respectively), when inoculated with PRRSV-1 field strains with 93.4% or 92.7% of nucleotide similarity with the MLV, respectively [68][70]. In another study, an estimate of R0 for the vaccinated contact group was approximately 5.0, one half of that observed for the unvaccinated contact group (mode R0 = 10) [71]. Given the pig ages, MLV and inoculated virus were diverse, different models resulted in different R0 values. However, these results consistently suggest that even when a leaky vaccine cannot completely prevent pigs from heterologous infection, it can still have beneficial impacts on the transmission dynamics, contributing to the reduced R0 value in a pig herd.

2.2. Homologous Protection

Presently, it is a relative consensus that PRRS MLV has the highest protective efficacy against the genetically homologous virus, compared with commercially available KV or other kinds of vaccines under development. Numerous publications have described the protective efficacy of MLV under experimental or field condition, around the United States, Europe, and Asia [72][73][74][75]. At the individual level, the efficacy of PRRS MLV is generally described as protective against both reproductive failure and respiratory disorders, providing multiple benefits including but not limited to the reduction of clinical signs, lessened macroscopic and microscopic lung lesion and viremia, shortened viral shedding period and reduced secondary bacterial infection [76][77][78][79]. Reports in a gilts vaccination and late pregnant term challenge study have shown that MLV vaccination can improve the reproductive performance in sows and piglet health and overall viability, compared with unvaccinated sows [80][81][82].

Indeed, there is no fixed “cutoff value” for genetic similarity to classify the “homologous” or “heterologous” strains, the efficacy of homologous protection conferred by PRRS MLV is difficult to be predicted by sequence comparison, especially only based on the sequence of GP5. For example, the Chinese HP-PRRSV-derived MLV such as JXA1-R (P80), HuN4-F112, and TJM-F92 were all described to protect piglets from the lethal challenge of homologous strains, showing no obvious body temperature increase nor other clinical signs throughout the experiment [83][84][85][86][87]. This high protection efficacy could also be observed in the field during the initial years of the HP-PRRSV pandemic. In contrast, another study has reported that Lelystad-like MLV only provides partial protection against the field isolate of the same cluster, suggesting that the degree of genetic homology of ORF5 between the MLV vaccine and challenge isolate is not a good predictor for vaccine efficacy [88]. This is reasonable, as there is no evidence to support that the GP5 encoded by ORF5 is the only protection-related viral protein.

2.3. Heterologous Cross-Protection

PRRSV is well characterized by its mutability, which continually leads to the generation of novel variants, frequently causing an outbreak or re-outbreak in PRRS-stable herds, in which pigs have been previously vaccinated or acclimatized [1][24][89]. Lack of providing satisfied heterologous cross-protection against the rapidly evolving virus is the obvious deficiency for most PRRS vaccines, not only for MLV. At the individual level, MLV vaccination usually cannot induce sterilizing immunity to completely block the infection of heterologous strains [59][89][90][91][92]. However, many experimental vaccination-challenge trials or field studies have indicated that PRRSV vaccination can provide partial protection against heterologous strains, shown as delaying the onset of viremia, reducing the duration of viral shedding and significantly decreasing viral load throughout infection, not showing severe clinical signs as unvaccinated animals [59][82][91][93][94][95][96][97][98][99].

To investigate the cross-protection efficacy of commercially available PRRSV-1 and PRRSV-2 MLV against each type of virus, serial vaccination-challenge studies in growing pigs and pregnant gilts were carried out by Chae’s group. The clinical signs including body temperature, respiratory scores, viremia, viral shedding, macroscopic and microscopic lung lesion scores, PRRSV-antigen distribution in interstitial pneumonia, and productive performance such as duration of pregnancy, the ratio of stillborn, and numbers of weaning pigs, together with PRRSV-specific IFN-γ secreting cells in PBMC were all evaluated and compared among two types of MLV-vaccinated groups and unvaccinated groups. Generally, their results indicated that PRRSV-2 MLV was capable of providing partial heterologous cross-protection against the PRRSV-1 virus, but PRRSV-1 MLV was ineffective against PRRSV-2. Importantly, they also found that either PRRSV-1 or PRRSV-2 -specific IFN-γ-secreting cells in the PRRSV-2 MLV-vaccinated group were higher than the PRRSV-1 MLV-vaccinated group, which was regarded to attribute to unidirectional cross-protection between PRRSV-1 and PRRSV-2 [86][95][96][97].

The internal-type cross-protection was also widely investigated. Lager et al. have tested the efficacy of Inglevac PRRS® MLV (from Boehringer Ingelheim, Ingelheim am Rhein, Germany) against Chinese and Vietnamese HP-PRRSV heterologous challenge in pigs, to demonstrate if this commercially available MLV in the United States could be used as an aid in the control of HP-PRRSV outbreaks. Their results indicated that vaccination decreased the duration of viremia and viral load, and shortened the time of high fever and reduced macroscopic lung lesions, compared with those of unvaccinated animals [86]. Similarly, after the United States-originated NADC30-like virus was identified to begin an epidemic in China, the cross-protection efficacy of commercially available vaccines against NADC30-like field strains was investigated by several research groups [92][100][101][102][103]. In our study, two commercial vaccines (JXA1-R and Inglevac PRRS® MLV) and an attenuated low pathogenic strain HB-1/3.9-P40 were used to vaccinate pigs with the same dose as 2 × 105 TCID50, the data showed that vaccination in all three groups could not fully reduce the severe level of clinical signs and lung lesions caused by the NADC30-like virus. However, the Ingelvac PRRS® MLV appeared to exert some beneficial effects on shortening the period of clinical fever and improving the growth performance of the challenged pigs [92]. The results of partial or limited cross-protection against the NADC30-like virus were also reported by other groups. The limited efficacy of cross-protection from commercial MLV vaccines against NADC30-like viruses might be an important reason that these viruses widely spread and became the predominant PRRSV strains in China [102][104][105][106]. Furthermore, the Fostera® PRRS MLV from lineage 8 of PRRSV-2 is also confirmed to confer partial cross-protection against the heterologous challenge of a virulent PRRSV strain from lineage 3 [107]. To improve the heterologous protection efficacy, some immune boosters or regulators, such as quercetin and Quil A, which are regarded to be able to upgrade the mRNA expression of interferon and many other helpful cytokines, were orally taken or injected together with PRRS MLV. However, any significant improvement in heterologous cross-protection was not observed [108][109]. Some typical vaccination-challenge (homologous or/and heterologous) studies on different types of MLV are summarized in Table 2.

Table 2. Studies on evaluating cross-protection efficacy of commercial MLV vaccines

MLV Challenge Virus Species/Types (MLV/Challenge) Homologous/Heterologous Tested Animals Parameters for Immune Response Results and Reference
Porcilis® PRRS PR40/2014 PRRSV-1/PRRSV-1 Heterologous Piglet Ab and NAb Triggered adaptive immunity against highly pathogenic strain, and reduced clinical indicators [110]
Amervac® PRRS KKU-PP2013 PRRSV-1/PRRSV-2 Heterologous Piglet Ab A certain degree of protection against the PRRSV-2 challenge [111]
Amervac® PRRS 01NP1 PRRSV-1/PRRSV-2 Heterologous Piglet Ab/IFN-α, IFN-β and IFN-γ Upregulated IFN-α, IFN-β, and inflammatory cytokines and reduced PRRSV-2 viremia and number of viremic pigs [109]
Fostera® PRRS SNUVR090485 PRRSV-2/PRRSV-1 Heterologous Piglet Ab/IFN-γ secreting cells Partial protection from the challenge of heterologous type 1 PRRSV and reduced viremia [96]
HuN4-F112 HuN4-F5 PRRSV-2/PRRSV-2 Homologous Piglet Ab and NAb Protection from the lethal challenge [84]
Ingelvac PRRS® MLV VR-2332-P6, rJXwn06-P3, rSRV07-P3 PRRSV-2/PRRSV-2 Homologous/heterologous Piglet Ab Partial protection against the homologous and heterologous PRRSV challenge [86]
JXA1-R HV-PRRSV, NADC-20 PRRSV-2/PRRSV-2 Homologous/heterologous Piglet Ab and NAb/IFN-α and IFN-β Protection from the challenge of HP-PRRSV or NADC-20, induced broadly neutralizing antibodies and enhanced pulmonary IFN-α/β production [74]
Ingelvac PRRS® MLV 10186-614 PRRSV-2/PRRSV-2 Heterologous Piglet Ab No prevention in viral shedding, reduced viral replication, and disease severity [112]
Ingelvac PRRS® MLV/JXA1-R/(HB-1/3.9-P40) CHsx1401(NADC30-like virus) PRRSV-2/PRRSV-2 Heterologous Piglet Ab Reduced clinical signs and lung lesions, shortening the period of clinical fever and improving the growth performance (Ingelvac PRRS® MLV) [92]
PrimePac® PRRS dss PRRSV-2/PRRSV-2 Heterologous Piglet Ab/Treg, IL-10, and IFN-γ Partial protection against the Thai HP-PRRSV, based on body temperature, levels of viremia, and lung lesion [113]
Ingelvac PRRS® MLV 1-4-4 PRRSV-2/PRRSV-2 Heterologous Piglet Ab and NAb/IFN-γ secreting cells (total lymphocytes, NK, CD4+, CD8+, and γδT cells) No improvement in the efficiency of cross-protection (adjuvant M. vaccae WCL or CpG ODN), induced virus-specific T cell response (IM vaccination) [114]
Fostera® PRRS SNUVR090485 PRRSV-2/PRRSV-1 Heterologous Gilt Ab/IFN-γ secreting cells Cross-protection against the PRRSV-1 challenge in late-term pregnant gilts, improved reproductive performance, and induced immunity lasting for 19 weeks at least [115]
Unistrain® PRRS SNUVR090485, SNUVR090851 PRRSV-1/(PRRSV-1 or PRRSV-2) Heterologous Gilt Ab/IFN-γ secreting cells Vaccinated pregnant sows with the PRRSV-1 MLV against PRRSV-1, but limited to PRRSV-2 in late-term pregnant gilts [80]
Ingelvac PRRS® MLV SNUVR090485, SNUVR100059 PRRSV-2/(PRRSV-1 or PRRSV-2) Heterologous Sow Ab/IFN-γ secreting cells Vaccinated pregnant sows with the PRRSV-2 MLV against PRRSV-2, but not to PRRSV-1 [116]
Unistrain® PRRS/Fostera® PRRS SNUVR090485, SNUVR090851 (PRRSV-1 or PRRSV-2)/(PRRSV-1 + PRRSV-2) Heterologous Gilt Ab/IFN-γ secreting cells PRRSV-2 MLV vaccine is more efficacious than PRRSV-1 MLV against the dual heterologous challenge in gilts [117]

Given the extensive genetic and antigenic variation of PRRSV, most situations in the field can be considered as a “heterologous challenge”, as the field strains are more or less different from the commercial vaccine strains. Thus, improving the heterologous or even providing broadened cross-protection is one of the major requirements for designing a perfect PRRS vaccine. However, the unclearness of the mechanism on immunological protection greatly hinders the progress of PRRS vaccine development.

3. Genetically Modified Live Virus Vaccine

Since the first RNA-launched infectious cDNA clone of the Lelystad virus, the PRRSV-1 prototype, was successfully constructed, more than 20 distinct PRRSV infectious clones have been generated [24]. With the platform of reverse genetic operation, it is possible to artificially edit the virus by point mutations, truncations, gene insertion or fragment swapping between different strains, to identify the virulence factors, cross-protection antigens, and other factors related to protective efficacy and vaccine safety, which will contribute to the development of PRRS vaccine. An informative table summarizing the knockouts and knockdowns of viral genes and their influence on the viruses was presented in a previous review [24]. Furthermore, various strategies have been documented based on the reverse genetic operation. In order to improve the heterologous protective efficacy, viral genes or clusters of genes from strains with different antigenic characterizations were swapped to create the chimeric viruses or the recombinant viruses carrying DNA shuffled fragments or the conserved fragment of sequence from multiple strains were constructed. In addition, codon pairs de-optimization was also used for rapid attenuation of the virus. As well, foreign fragment including B-cell epitope, protective antigen, and adjuvant cytokines were inserted into the genome of PRRSV to create a marker vaccine, multivalent vaccine or protective efficacy-improved vaccine. These novel strategies and approaches to develop the next generation of vaccines have been well-reviewed before [11][41].

This entry is adapted from the peer-reviewed paper 10.3390/vaccines9040362

References

  1. Vu, H.L.; Pattnaik, A.K.; Osorio, F.A. Strategies to broaden the cross-protective efficacy of vaccines against porcine reproductive and respiratory syndrome virus. Vet. Microbiol. 2017, 206, 29–34.
  2. Lunney, J.K.; Benfield, D.A.; Rowland, R.R. Porcine reproductive and respiratory syndrome virus: An update on an emerging and re-emerging viral disease of swine. Virus Res. 2010, 154, 1–6.
  3. Wensvoort, G. Lelystad virus and the porcine epidemic abortion and respiratory syndrome. Vet. Res. 1993, 24, 117–124.
  4. Zeman, D.; Neiger, R.; Yaeger, M.; Nelson, E.; Benfield, D.; Leslie-Steen, P.; Thomson, J.; Miskimins, D.; Daly, R.; Minehart, M. Laboratory Investigation of PRRS Virus Infection in Three Swine Herds. J. Vet. Diagn. Investig. 1993, 5, 522–528.
  5. Baron, T.; Albina, E.; Leforban, Y.; Madec, F.; Guilmoto, H.; Duran, J.P.; Vannier, P. Report on the first outbreaks of the porcine reproductive and respiratory syndrome (PRRS) in France. Diagnosis and viral isolation. Ann. Rech. Vet. 1992, 23, 161–166.
  6. Zhou, L.; Yang, H. Porcine reproductive and respiratory syndrome in China. Virus Res. 2010, 154, 31–37.
  7. Karniychuk, U.U.; Geldhof, M.; Vanhee, M.; Van Doorsselaere, J.; Saveleva, T.A.; Nauwynck, H.J. Pathogenesis and antigenic characterization of a new East European subtype 3 porcine reproductive and respiratory syndrome virus isolate. BMC Vet. Res. 2010, 6, 30.
  8. Tian, K.; Yu, X.; Zhao, T.; Feng, Y.; Cao, Z.; Wang, C.; Hu, Y.; Chen, X.; Hu, D.; Tian, X.; et al. Emergence of Fatal PRRSV Variants: Unparalleled Outbreaks of Atypical PRRS in China and Molecular Dissection of the Unique Hallmark. PLoS ONE 2007, 2, e526.
  9. Zhou, L.; Chen, S.; Zhang, J.; Zeng, J.; Guo, X.; Ge, X.; Zhang, D.; Yang, H. Molecular variation analysis of porcine reproductive and respiratory syndrome virus in China. Virus Res. 2009, 145, 97–105.
  10. Zhou, L.; Zhang, J.; Zeng, J.; Yin, S.; Li, Y.; Zheng, L.; Guo, X.; Ge, X.; Yang, H. The 30-Amino-Acid Deletion in the Nsp2 of Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus Emerging in China Is Not Related to Its Virulence. J. Virol. 2009, 83, 5156–5167.
  11. Nan, Y.; Wu, C.; Gu, G.; Sun, W.; Zhang, Y.-J.; Zhou, E.-M. Improved Vaccine against PRRSV: Current Progress and Future Perspective. Front. Microbiol. 2017, 8, 1635.
  12. Lunney, J.K.; Fang, Y.; Ladinig, A.; Chen, N.; Li, Y.; Rowland, B.; Renukaradhya, G.J. Porcine Reproductive and Respiratory Syndrome Virus (PRRSV): Pathogenesis and Interaction with the Immune System. Annu. Rev. Anim. Biosci. 2016, 4, 129–154.
  13. Adams, M.J.; Lefkowitz, E.J.; King, A.M.Q.; Harrach, B.; Harrison, R.L.; Knowles, N.J.; Kropinski, A.M.; Krupovic, M.; Kuhn, J.H.; Mushegian, A.R.; et al. Ratification vote on taxonomic proposals to the International Committee on Taxonomy of Viruses (2016). Arch. Virol. 2016, 161, 2921–2949.
  14. Collins, J.E.; Benfield, D.A.; Christianson, W.T.; Harris, L.; Hennings, J.C.; Shaw, D.P.; Goyal, S.M.; McCullough, S.; Morrison, R.B.; Joo, H.S.; et al. Isolation of Swine Infertility and Respiratory Syndrome Virus (Isolate ATCC VR-2332) in North America and Experimental Reproduction of the Disease in Gnotobiotic Pigs. J. Vet. Diagn. Investig. 1992, 4, 117–126.
  15. Halbur, P.G.; Paul, P.S.; Frey, M.L.; Landgraf, J.; Eernisse, K.; Meng, X.-J.; Lum, M.A.; Andrews, J.J.; Rathje, J.A. Comparison of the Pathogenicity of Two US Porcine Reproductive and Respiratory Syndrome Virus Isolates with that of the Lelystad Virus. Vet. Pathol. 1995, 32, 648–660.
  16. Christianson, W.T.; Choi, C.S.; Collins, J.E.; Molitor, T.W.; Morrison, R.B.; Joo, H.S. Pathogenesis of porcine reproductive and respiratory syndrome virus infection in mid-gestation sows and fetuses. Can. J. Vet. Res. 1993, 57, 262–268.
  17. Shi, M.; Lam, T.T.-Y.; Hon, C.-C.; Murtaugh, M.P.; Davies, P.R.; Hui, R.K.-H.; Li, J.; Wong, L.T.-W.; Yip, C.-W.; Jiang, J.-W.; et al. Phylogeny-Based Evolutionary, Demographical, and Geographical Dissection of North American Type 2 Porcine Reproductive and Respiratory Syndrome Viruses. J. Virol. 2010, 84, 8700–8711.
  18. Shi, M.; Lam, T.T.-Y.; Hon, C.-C.; Hui, R.K.-H.; Faaberg, K.S.; Wennblom, T.; Murtaugh, M.P.; Stadejek, T.; Leung, F.C.-C. Molecular epidemiology of PRRSV: A phylogenetic perspective. Virus Res. 2010, 154, 7–17.
  19. Goldberg, T.L.; Lowe, J.F.; Milburn, S.M.; Firkins, L.D. Quasispecies variation of porcine reproductive and respiratory syndrome virus during natural infection. Virology 2003, 317, 197–207.
  20. Meng, X.J. Emerging and Re-emerging Swine Viruses. Transbound. Emerg. Dis. 2012, 59, 85–102.
  21. Murtaugh, M.P.; Stadejek, T.; Abrahante, J.E.; Lam, T.T.; Leung, F.C.-C. The ever-expanding diversity of porcine reproductive and respiratory syndrome virus. Virus Res. 2010, 154, 18–30.
  22. Morgan, A.; Poland, G.A. The Jenner Society and the Edward Jenner Museum: Tributes to a physician-scientist. Vaccine 2011, 29, D152–D154.
  23. Bloom, D.E.; Black, S.; Salisbury, D.; Rappuoli, R. Antimicrobial resistance and the role of vaccines. Proc. Natl. Acad. Sci. USA 2018, 115, 12868–12871.
  24. Renukaradhya, G.J.; Meng, X.-J.; Calvert, J.G.; Roof, M.; Lager, K.M. Live porcine reproductive and respiratory syndrome virus vaccines: Current status and future direction. Vaccine 2015, 33, 4069–4080.
  25. Hu, J.; Zhang, C. Porcine Reproductive and Respiratory Syndrome Virus Vaccines: Current Status and Strategies to a Universal Vaccine. Transbound. Emerg. Dis. 2013, 61, 109–120.
  26. Kimman, T.G.; Cornelissen, L.A.; Moormann, R.J.; Rebel, J.M.; Stockhofe-Zurwieden, N. Challenges for porcine reproductive and respiratory syndrome virus (PRRSV) vaccinology. Vaccine 2009, 27, 3704–3718.
  27. Read, A.F.; Baigent, S.J.; Powers, C.; Kgosana, L.B.; Blackwell, L.; Smith, L.P.; Kennedy, D.A.; Walkden-Brown, S.W.; Nair, V.K. Imperfect Vaccination Can Enhance the Transmission of Highly Virulent Pathogens. PLoS Biol. 2015, 13, e1002198.
  28. Kupferschmidt, K. Risk of ‘leaky’ vaccines debated. Science 2015, 349, 461–462.
  29. Costers, S.; Lefebvre, D.J.; Delputte, P.L.; Nauwynck, H.J. Porcine reproductive and respiratory syndrome virus modulates apoptosis during replication in alveolar macrophages. Arch. Virol. 2008, 153, 1453–1465.
  30. Lager, K.M.; Mengeling, W.L.; Brockmeier, S.L. Evaluation of protective immunity in gilts inoculated with the NADC-8 isolate of porcine reproductive and respiratory syndrome virus (PRRSV) and challenge-exposed with an antigenically distinct PRRSV isolate. Am. J. Vet. Res. 1999, 60, 1022–1027.
  31. Renukaradhya, G.J.; Meng, X.-J.; Calvert, J.G.; Roof, M.; Lager, K.M. Inactivated and subunit vaccines against porcine reproductive and respiratory syndrome: Current status and future direction. Vaccine 2015, 33, 3065–3072.
  32. Mulupuri, P.; Zimmerman, J.J.; Hermann, J.; Johnson, C.R.; Cano, J.P.; Yu, W.; Dee, S.A.; Murtaugh, M.P. Antigen-Specific B-Cell Responses to Porcine Reproductive and Respiratory Syndrome Virus Infection. J. Virol. 2007, 82, 358–370.
  33. Foss, D.L.; Zilliox, M.J.; Meier, W.; Zuckermann, F.; Murtaugh, M.P. Adjuvant Danger Signals Increase the Immune Response to Porcine Reproductive and Respiratory Syndrome Virus. Viral Immunol. 2002, 15, 557–566.
  34. Rahe, M.C.; Murtaugh, M.P. Effector mechanisms of humoral immunity to porcine reproductive and respiratory syndrome virus. Vet. Immunol. Immunopathol. 2017, 186, 15–18.
  35. Rahe, M.C.; Gustafson, K.L.; Murtaugh, M.P. B Cell Tetramer Development for Veterinary Vaccinology. Viral Immunol. 2018, 31, 1–10.
  36. Rahe, M.C.; Dvorak, C.M.T.; Patterson, A.; Roof, M.; Murtaugh, M.P. The PRRSV-Specific Memory B Cell Response Is Long-Lived in Blood and Is Boosted During Live Virus Re-exposure. Front. Immunol. 2020, 11, 247.
  37. Chen, Z.; Earl, P.; Americo, J.; Damon, I.; Smith, S.K.; Zhou, Y.-H.; Yu, F.; Sebrell, A.; Emerson, S.; Cohen, G.; et al. Chimpanzee/human mAbs to vaccinia virus B5 protein neutralize vaccinia and smallpox viruses and protect mice against vaccinia virus. Proc. Natl. Acad. Sci. USA 2006, 103, 1882–1887.
  38. Shrestha, B.; Brien, J.D.; Sukupolvi-Petty, S.; Austin, S.K.; Edeling, M.A.; Kim, T.; O’Brien, K.M.; Nelson, C.A.; Johnson, S.; Fremont, D.H.; et al. The Development of Therapeutic Antibodies That Neutralize Homologous and Heterologous Genotypes of Dengue Virus Type 1. PLoS Pathog. 2010, 6, e1000823.
  39. Tsukamoto, M.; Hiroi, S.; Adachi, K.; Kato, H.; Inai, M.; Konishi, I.; Tanaka, M.; Yamamoto, R.; Sawa, M.; Handharyani, E. Antibodies against swine influenza virus neutralize the pandemic influenza virus A/H1N1. Mol. Med. Rep. 2011, 4, 209–214.
  40. Yoon, K.-J.; Zimmerman, J.J.; Swenson, S.L.; McGinley, M.J.; Eernisse, K.A.; Brevik, A.; Rhinehart, L.L.; Frey, M.L.; Hill, H.T.; Platt, K.B. Characterization of the Humoral Immune Response to Porcine Reproductive and Respiratory Syndrome (PRRS) Virus Infection. J. Vet. Diagn. Investig. 1995, 7, 305–312.
  41. Yoon, K.-J.; Wu, L.-L.; Zimmerman, J.J.; Hill, H.T.; Platt, K.B. Antibody-Dependent Enhancement (ADE) of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Infection in Pigs. Viral Immunol. 1996, 9, 51–63.
  42. Van Breedam, W.; Costers, S.; Vanhee, M.; Gagnon, C.A.; Rodríguez-Gómez, I.M.; Geldhof, M.; Verbeeck, M.; Van Doorsselaere, J.; Karniychuk, U.; Nauwynck, H.J. Porcine reproductive and respiratory syndrome virus (PRRSV)-specific mAbs: Supporting diagnostics and providing new insights into the antigenic properties of the virus. Vet. Immunol. Immunopathol. 2011, 141, 246–257.
  43. Li, J.; Murtaugh, M.P. Dissociation of porcine reproductive and respiratory syndrome virus neutralization from antibodies specific to major envelope protein surface epitopes. Virology 2012, 433, 367–376.
  44. Vanhee, M.; Van Breedam, W.; Costers, S.; Geldhof, M.; Noppe, Y.; Nauwynck, H. Characterization of antigenic regions in the porcine reproductive and respiratory syndrome virus by the use of peptide-specific serum antibodies. Vaccine 2011, 29, 4794–4804.
  45. Lee, C.; Rogan, D.; Erickson, L.; Zhang, J.; Yoo, D. Characterization of the porcine reproductive and respiratory syndrome virus glycoprotein 5 (GP5) in stably expressing cells. Virus Res. 2004, 104, 33–38.
  46. Wissink, E.H.J.; Kroese, M.V.; Van Wijk, H.A.R.; Rijsewijk, F.A.M.; Meulenberg, J.J.M.; Rottier, P.J.M. Envelope Protein Requirements for the Assembly of Infectious Virions of Porcine Reproductive and Respiratory Syndrome Virus. J. Virol. 2005, 79, 12495–12506.
  47. Das, P.B.; Vu, H.L.; Dinh, P.X.; Cooney, J.L.; Kwon, B.; Osorio, F.A.; Pattnaik, A.K. Glycosylation of minor envelope glycoproteins of porcine reproductive and respiratory syndrome virus in infectious virus recovery, receptor interaction, and immune response. Virology 2011, 410, 385–394.
  48. Guo, R.; Katz, B.B.; Tomich, J.M.; Gallagher, T.; Fang, Y. Porcine Reproductive and Respiratory Syndrome Virus Utilizes Nanotubes for Intercellular Spread. J. Virol. 2016, 90, 5163–5175.
  49. Wang, T.; Fang, L.; Zhao, F.; Wang, D.; Xiao, S. Exosomes mediate intercellular transmission of porcine reproductive and respiratory syndrome virus (PRRSV). J. Virol. 2017, 92.
  50. Su, J.; Zhou, L.; He, B.; Zhang, X.; Ge, X.; Han, J.; Guo, X.; Yang, H. Nsp2 and GP5-M of Porcine Reproductive and Respiratory Syndrome Virus Contribute to Targets for Neutralizing Antibodies. Virol. Sin. 2019, 34, 631–640.
  51. Osorio, F.; Galeota, J.; Nelson, E.; Brodersen, B.; Doster, A.; Wills, R.; Zuckermann, F.; Laegreid, W. Passive Transfer of Virus-Specific Antibodies Confers Protection against Reproductive Failure Induced by a Virulent Strain of Porcine Reproductive and Respiratory Syndrome Virus and Establishes Sterilizing Immunity. Virology 2002, 302, 9–20.
  52. Molina, R.; Cha, S.-H.; Chittick, W.; Lawson, S.; Murtaugh, M.; Nelson, E.; Christopher-Hennings, J.; Yoon, K.-J.; Evans, R.; Rowland, R.; et al. Immune response against porcine reproductive and respiratory syndrome virus during acute and chronic infection. Vet. Immunol. Immunopathol. 2008, 126, 283–292.
  53. Labarque, G.G.; Nauwynck, H.J.; Van Reeth, K.; Pensaert, M.B. Effect of cellular changes and onset of humoral immunity on the replication of porcine reproductive and respiratory syndrome virus in the lungs of pigs. J. Gen. Virol. 2000, 81, 1327–1334.
  54. Robinson, S.R.; Li, J.; Nelson, E.A.; Murtaugh, M.P. Broadly neutralizing antibodies against the rapidly evolving porcine reproductive and respiratory syndrome virus. Virus Res. 2015, 203, 56–65.
  55. Robinson, S.R.; Rahe, M.C.; Gray, D.K.; Martins, K.V.; Murtaugh, M.P. Porcine reproductive and respiratory syndrome virus neutralizing antibodies provide In Vivo cross-protection to PRRSV1 and PRRSV2 viral challenge. Virus Res. 2018, 248, 13–23.
  56. Bautista, E.M.; Molitor, T.W. Cell-Mediated Immunity to Porcine Reproductive and Respiratory Syndrome Virus in Swine. Viral Immunol. 1997, 10, 83–94.
  57. Lowe, J.F.; Husmann, R.; Firkins, L.D.; Zuckermann, F.A.; Goldberg, T.L. Correlation of cell-mediated immunity against porcine reproductive and respiratory syndrome virus with protection against reproductive failure in sows during outbreaks of porcine reproductive and respiratory syndrome in commercial herds. J. Am. Vet. Med. Assoc. 2005, 226, 1707–1711.
  58. Madapong, A.; Saeng-Chuto, K.; Boonsoongnern, A.; Tantituvanont, A.; Nilubol, D. Cell-mediated immune response and protective efficacy of porcine reproductive and respiratory syndrome virus modified-live vaccines against co-challenge with PRRSV-1 and PRRSV-2. Sci. Rep. 2020, 10, 1649.
  59. Martelli, P.; Gozio, S.; Ferrari, L.; Rosina, S.; De Angelis, E.; Quintavalla, C.; Bottarelli, E.; Borghetti, P. Efficacy of a modified live porcine reproductive and respiratory syndrome virus (PRRSV) vaccine in pigs naturally exposed to a heterologous European (Italian cluster) field strain: Clinical protection and cell-mediated immunity. Vaccine 2009, 27, 3788–3799.
  60. Sang, Y.; Rowland, R.R.R.; Blecha, F. Interaction between innate immunity and porcine reproductive and respiratory syndrome virus. Anim. Health Res. Rev. 2011, 12, 149–167.
  61. Sun, Y.; Han, M.; Kim, C.; Calvert, J.G.; Yoo, D. Interplay between Interferon-Mediated Innate Immunity and Porcine Reproductive and Respiratory Syndrome Virus. Viruses 2012, 4, 424–446.
  62. Islam, A.; Große-Brinkhaus, C.; Pröll, M.J.; Uddin, M.J.; Rony, S.A.; Tesfaye, D.; Tholen, E.; Hoelker, M.; Schellander, K.; Neuhoff, C. PBMC transcriptome profiles identifies potential candidate genes and functional networks controlling the innate and the adaptive immune response to PRRSV vaccine in Pietrain pig. PLoS ONE 2017, 12, e0171828.
  63. Islam, A.; Große-Brinkhaus, C.; Pröll, M.J.; Uddin, M.J.; Rony, S.A.; Tesfaye, D.; Tholen, E.; Hölker, M.; Schellander, K.; Neuhoff, C. Deciphering transcriptome profiles of peripheral blood mononuclear cells in response to PRRSV vaccination in pigs. BMC Genom. 2016, 17, 641.
  64. Pileri, E.; Mateu, E. Review on the transmission porcine reproductive and respiratory syndrome virus between pigs and farms and impact on vaccination. Vet. Res. 2016, 47, 108.
  65. Arruda, A.G.; Tousignant, S.; Sanhueza, J.; Vilalta, C.; Poljak, Z.; Torremorell, M.; Alonso, C.; Corzo, C.A. Aerosol Detection and Transmission of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV): What Is the Evidence, and What Are the Knowledge Gaps? Viruses 2019, 11, 712.
  66. Böttcher, J.; Alex, M.; Janowetz, B.; Müller, S.; Schuh, C.; Niemeyer, H. The PRRSV-serumneutralization test detects gaps in herd immunity. Berl. Munch. Tierarztl. Wochenschr. 2014, 127, 305–313.
  67. Pileri, E.; Gibert, E.; Martín-Valls, G.; Nofrarias, M.; López-Soria, S.; Martín, M.; Díaz, I.; Darwich, L.; Mateu, E. Transmission of Porcine reproductive and respiratory syndrome virus 1 to and from vaccinated pigs in a one-to-one model. Vet. Microbiol. 2017, 201, 18–25.
  68. Pileri, E.; Gibert, E.; Soldevila, F.; García-Saenz, A.; Pujols, J.; Diaz, I.; Darwich, L.; Casal, J.; Martín, M.; Mateu, E. Vaccination with a genotype 1 modified live vaccine against porcine reproductive and respiratory syndrome virus significantly reduces viremia, viral shedding and transmission of the virus in a quasi-natural experimental model. Vet. Microbiol. 2015, 175, 7–16.
  69. Pileri, E.; Martín-Valls, G.E.; Díaz, I.; Allepuz, A.; Simon-Grifé, M.; García-Saenz, A.; Casal, J.; Mateu, E. Estimation of the transmission parameters for swine influenza and porcine reproductive and respiratory syndrome viruses in pigs from weaning to slaughter under natural conditions. Prev. Vet. Med. 2017, 138, 147–155.
  70. Rose, N.; Renson, P.; Andraud, M.; Paboeuf, F.; Le Potier, M.; Bourry, O. Porcine reproductive and respiratory syndrome virus (PRRSv) modified-live vaccine reduces virus transmission in experimental conditions. Vaccine 2015, 33, 2493–2499.
  71. Chase-Topping, M.; Xie, J.; Pooley, C.; Trus, I.; Bonckaert, C.; Rediger, K.; Bailey, R.I.; Brown, H.; Bitsouni, V.; Barrio, M.B.; et al. New insights about vaccine effectiveness: Impact of attenuated PRRS-strain vaccination on heterologous strain transmission. Vaccine 2020, 38, 3050–3061.
  72. Guo, B.; Lager, K.M.; Henningson, J.N.; Miller, L.C.; Schlink, S.N.; Kappes, M.A.; Kehrli, M.E.; Brockmeier, S.L.; Nicholson, T.L.; Yang, H.-C.; et al. Experimental infection of United States swine with a Chinese highly pathogenic strain of porcine reproductive and respiratory syndrome virus. Virology 2013, 435, 372–384.
  73. Lowe, J.F.; Zuckermann, F.A.; Firkins, L.D.; Schnitzlein, W.M.; Goldberg, T.L. Immunologic responses and reproductive outcomes following exposure to wild-type or attenuated porcine reproductive and respiratory syndrome virus in swine under field conditions. J. Am. Vet. Med. Assoc. 2006, 228, 1082–1088.
  74. Galliher-Beckley, A.; Li, X.; Bates, J.T.; Madera, R.; Waters, A.; Nietfeld, J.; Henningson, J.; He, N.; Feng, W.; Chen, R.; et al. Pigs immunized with Chinese highly pathogenic PRRS virus modified live vaccine are protected from challenge with North American PRRSV strain NADC-20. Vaccine 2015, 33, 3518–3525.
  75. Renson, P.; Fablet, C.; Le Dimna, M.; Mahé, S.; Touzain, F.; Blanchard, Y.; Paboeuf, F.; Rose, N.; Bourry, O. Preparation for emergence of an Eastern European porcine reproductive and respiratory syndrome virus (PRRSV) strain in Western Europe: Immunization with modified live virus vaccines or a field strain confers partial protection. Vet. Microbiol. 2017, 204, 133–140.
  76. Ellingson, J.S.; Wang, Y.; Layton, S.; Ciacci-Zanella, J.; Roof, M.B.; Faaberg, K.S. Vaccine efficacy of porcine reproductive and respiratory syndrome virus chimeras. Vaccine 2010, 28, 2679–2686.
  77. Dwivedi, V.; Manickam, C.; Patterson, R.; Dodson, K.; Murtaugh, M.; Torrelles, J.B.; Schlesinger, L.S.; Renukaradhya, G.J. Cross-protective immunity to porcine reproductive and respiratory syndrome virus by intranasal delivery of a live virus vaccine with a potent adjuvant. Vaccine 2011, 29, 4058–4066.
  78. Cano, J.P.; Dee, S.A.; Murtaugh, M.P.; Trincado, C.A.; Pijoan, C.B. Effect of vaccination with a modified-live porcine reproductive and respiratory syndrome virus vaccine on dynamics of homologous viral infection in pigs. Am. J. Vet. Res. 2007, 68, 565–571.
  79. Linhares, D.C.; Cano, J.P.; Wetzell, T.; Nerem, J.; Torremorell, M.; Dee, S.A. Effect of modified-live porcine reproductive and respiratory syndrome virus (PRRSv) vaccine on the shedding of wild-type virus from an infected population of growing pigs. Vaccine 2012, 30, 407–413.
  80. Jeong, J.; Kang, I.; Kim, S.; Park, S.-J.; Park, K.H.; Oh, T.; Yang, S.; Chae, C. A modified-live porcine reproductive and respiratory syndrome virus (PRRSV)-1 vaccine protects late-term pregnancy gilts against heterologous PRRSV-1 but not PRRSV-2 challenge. Transbound. Emerg. Dis. 2018, 65, 1227–1234.
  81. Yang, S.; Oh, T.; Kang, I.; Park, S.-J.; Chae, C. Efficacy of concurrent vaccination with modified-live PRRSV-1 and PRRSV-2 vaccines against heterologous dual PRRSV-1 and PRRSV-2 challenge in late term pregnancy gilts. Vet. Microbiol. 2019, 239, 108497.
  82. Yang, S.; Kang, I.; Cho, H.; Oh, T.; Park, K.H.; Min, K.D.; Chae, C. A modified-live porcine reproductive and respiratory syndrome virus (PRRSV) vaccine protects late-term pregnancy gilts against a heterologous PRRSV-2 challenge. Can. J. Vet. Res. 2020, 84, 172–180.
  83. Yu, X.; Zhou, Z.; Cao, Z.; Wu, J.; Zhang, Z.; Xu, B.; Wang, C.; Hu, D.; Deng, X.; Han, W.; et al. Assessment of the Safety and Efficacy of an Attenuated Live Vaccine Based on Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus. Clin. Vaccine Immunol. 2015, 22, 493–502.
  84. Tian, Z.-J.; An, T.-Q.; Zhou, Y.-J.; Peng, J.-M.; Hu, S.-P.; Wei, T.-C.; Jiang, Y.-F.; Xiao, Y.; Tong, G.-Z. An attenuated live vaccine based on highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) protects piglets against HP-PRRS. Vet. Microbiol. 2009, 138, 34–40.
  85. Wang, G.; Song, T.; Yu, Y.; Liu, Y.; Shi, W.; Wang, S.; Rong, F.; Dong, J.; Liu, H.; Cai, X.; et al. Immune responses in piglets infected with highly pathogenic porcine reproductive and respiratory syndrome virus. Vet. Immunol. Immunopathol. 2011, 142, 170–178.
  86. Lager, K.M.; Schlink, S.N.; Brockmeier, S.L.; Miller, L.C.; Henningson, J.N.; Kappes, M.A.; Kehrli, M.E.; Loving, C.L.; Guo, B.; Swenson, S.L.; et al. Efficacy of Type 2 PRRSV vaccine against Chinese and Vietnamese HP-PRRSV challenge in pigs. Vaccine 2014, 32, 6457–6462.
  87. Leng, X.; Li, Z.; Xia, M.; He, Y.; Wu, H. Evaluation of the Efficacy of an Attenuated Live Vaccine against Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus in Young Pigs. Clin. Vaccine Immunol. 2012, 19, 1199–1206.
  88. Prieto, C.; Álvarez, E.; Martínez-Lobo, F.J.; Simarro, I.; Castro, J.M. Similarity of European porcine reproductive and respiratory syndrome virus strains to vaccine strain is not necessarily predictive of the degree of protective immunity conferred. Vet. J. 2008, 175, 356–363.
  89. Kiss, I.; Sámi, L.; Kecskeméti, S.; Hanada, K. Genetic variation of the prevailing porcine respiratory and reproductive syndrome viruses occurring on a pig farm upon vaccination. Arch. Virol. 2006, 151, 2269–2276.
  90. Bøtner, A.; Nielsen, J.; Oleksiewicz, M.B.; Storgaard, T. Heterologous challenge with porcine reproductive and respiratory syndrome (PRRS) vaccine virus: No evidence of reactivation of previous European-type PRRS virus infection. Vet. Microbiol. 1999, 68, 187–195.
  91. Scortti, M.; Prieto, C.; Simarro, I.; Castro, J.M. Reproductive performance of gilts following vaccination and subsequent heterologous challenge with European strains of porcine reproductive and respiratory syndrome virus. Theriogenology 2006, 66, 1884–1893.
  92. Zhou, L.; Yang, B.; Xu, L.; Jin, H.; Ge, X.; Guo, X.; Han, J.; Yang, H. Efficacy evaluation of three modified-live virus vaccines against a strain of porcine reproductive and respiratory syndrome virus NADC30-like. Vet. Microbiol. 2017, 207, 108–116.
  93. Li, X.; Galliher-Beckley, A.; Pappan, L.; Trible, B.; Kerrigan, M.; Beck, A.; Hesse, R.; Blecha, F.; Nietfeld, J.C.; Rowland, R.R.; et al. Comparison of Host Immune Responses to Homologous and Heterologous Type II Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Challenge in Vaccinated and Unvaccinated Pigs. BioMed Res. Int. 2014, 2014, 1–10.
  94. Park, C.; Seo, H.W.; Han, K.; Kang, I.; Chae, C. Evaluation of the efficacy of a new modified live porcine reproductive and respiratory syndrome virus (PRRSV) vaccine (Fostera PRRS) against heterologous PRRSV challenge. Vet. Microbiol. 2014, 172, 432–442.
  95. Kim, T.; Park, C.; Choi, K.; Jeong, J.; Kang, I.; Park, S.-J.; Chae, C. Comparison of Two Commercial Type 1 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Modified Live Vaccines against Heterologous Type 1 and Type 2 PRRSV Challenge in Growing Pigs. Clin. Vaccine Immunol. 2015, 22, 631–640.
  96. Park, C.; Choi, K.; Jeong, J.; Chae, C. Cross-protection of a new type 2 porcine reproductive and respiratory syndrome virus (PRRSV) modified live vaccine (Fostera PRRS) against heterologous type 1 PRRSV challenge in growing pigs. Vet. Microbiol. 2015, 177, 87–94.
  97. Choi, K.; Park, C.; Jeong, J.; Kang, I.; Park, S.-J.; Chae, C. Comparison of commercial type 1 and type 2 PRRSV vaccines against heterologous dual challenge. Vet. Rec. 2016, 178, 291.
  98. Calvert, J.G.; Keith, M.L.; Pearce, D.S.; Lenz, M.C.; King, V.L.; Diamondidis, Y.A.; Ankenbauer, R.G.; Martinon, N.C. Vaccination against porcine reproductive and respiratory syndrome virus (PRRSV) reduces the magnitude and duration of viremia following challenge with a virulent heterologous field strain. Vet. Microbiol. 2017, 205, 80–83.
  99. Oh, T.; Kim, H.; Park, K.H.; Yang, S.; Jeong, J.; Kim, S.; Kang, I.; Park, S.-J.; Chae, C. Comparison of 4 commercial modified-live porcine reproductive and respiratory syndrome virus (PRRSV) vaccines against heterologous Korean PRRSV-1 and PRRSV-2 challenge. Can. J. Vet. Res. 2019, 83, 57–67.
  100. Bai, X.; Wang, Y.; Xu, X.; Sun, Z.; Xiao, Y.; Ji, G.; Li, Y.; Tan, F.; Li, X.; Tian, K. Commercial vaccines provide limited protection to NADC30-like PRRSV infection. Vaccine 2016, 34, 5540–5545.
  101. Chai, W.; Liu, Z.; Sun, Z.; Su, L.; Zhang, C.; Huang, L. Efficacy of two porcine reproductive and respiratory syndrome (PRRS) modified-live virus (MLV) vaccines against heterologous NADC30-like PRRS virus challenge. Vet. Microbiol. 2020, 248, 108805.
  102. Tian, K. NADC30-Like Porcine Reproductive and Respiratory Syndrome in China. Open Virol. J. 2017, 11, 59–65.
  103. Zhang, H.; Xia, M.; Wang, W.; Ju, D.; Cao, L.; Wu, B.; Wang, X.; Wu, Y.; Song, N.; Hu, J.; et al. An Attenuated Highly Pathogenic Chinese PRRS Viral Vaccine Confers Cross Protection to Pigs against Challenge with the Emerging PRRSV NADC30-Like Strain. Virol. Sin. 2018, 33, 153–161.
  104. Zhou, L.; Wang, Z.; Ding, Y.; Ge, X.; Guo, X.; Yang, H. NADC30-like Strain of Porcine Reproductive and Respiratory Syndrome Virus, China. Emerg. Infect. Dis. 2015, 21, 2256–2257.
  105. Li, C.; Zhuang, J.; Wang, J.; Han, L.; Sun, Z.; Xiao, Y.; Ji, G.; Li, Y.; Tan, F.; Li, X.; et al. Outbreak Investigation of NADC30-Like PRRSV in South-East China. Transbound. Emerg. Dis. 2016, 63, 474–479.
  106. Jiang, Y.; Li, G.; Yu, L.; Li, L.; Zhang, Y.; Zhou, Y.; Tong, W.; Liu, C.; Gao, F.; Tong, G. Genetic Diversity of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) From 1996 to 2017 in China. Front. Microbiol. 2020, 11, 618.
  107. Hou, F.-H.; Lee, W.-C.; Liao, J.-W.; Chien, M.-S.; Kuo, C.-J.; Chung, H.-P.; Chia, M.-Y. Evaluation of a type 2 modified live porcine reproductive and respiratory syndrome vaccine against heterologous challenge of a lineage 3 highly virulent isolate in pigs. PeerJ 2020, 8, e8840.
  108. Ruansit, W.; Charerntantanakul, W. Oral supplementation of quercetin in PRRSV-1 modified-live virus vaccinated pigs in response to HP-PRRSV-2 challenge. Vaccine 2020, 38, 3570–3581.
  109. Charerntantanakul, W.; Pongjaroenkit, S. Co-administration of saponin quil A and PRRSV-1 modified-live virus vaccine up-regulates gene expression of type I interferon-regulated gene, type I and II interferon, and inflammatory cytokines and reduces viremia in response to PRRSV-2 challenge. Vet. Immunol. Immunopathol. 2018, 205, 24–34.
  110. Canelli, E.; Catella, A.; Borghetti, P.; Ferrari, L.; Ogno, G.; De Angelis, E.; Bonilauri, P.; Guazzetti, S.; Nardini, R.; Martelli, P. Efficacy of a modified-live virus vaccine in pigs experimentally infected with a highly pathogenic porcine reproductive and respiratory syndrome virus type 1 (HP-PRRSV-1). Vet. Microbiol. 2018, 226, 89–96.
  111. Ko, S.-S.; Seo, S.-W.; Sunwoo, S.-Y.; Yoo, S.J.; Kim, M.-H.; Lyoo, Y.S. Efficacy of commercial genotype 1 porcine reproductive and respiratory syndrome virus (PRRSV) vaccine against field isolate of genotype 2 PRRSV. Vet. Immunol. Immunopathol. 2016, 172, 43–49.
  112. Iseki, H.; Kawashima, K.; Tung, N.; Inui, K.; Ikezawa, M.; Shibahara, T.; Yamakawa, M. Efficacy of Type 2 porcine reproductive and respiratory syndrome virus (PRRSV) vaccine against the 2010 isolate of Vietnamese highly pathogenic PRRSV challenge in pigs. J. Vet. Med. Sci. 2017, 79, 765–773.
  113. Sirisereewan, C.; Woonwong, Y.; Arunorat, J.; Kedkovid, R.; Nedumpun, T.; Kesdangsakonwut, S.; Suradhat, S.; Thanawongnuwech, R.; Teankum, K. Efficacy of a type 2 PRRSV modified live vaccine (PrimePac™ PRRS) against a Thai HP-PRRSV challenge. Trop. Anim. Health Prod. 2018, 50, 1509–1518.
  114. Ouyang, K.; Hiremath, J.; Binjawadagi, B.; Shyu, D.-L.; Dhakal, S.; Arcos, J.; Schleappi, R.; Holman, L.; Roof, M.; Torrelles, J.B.; et al. Comparative analysis of routes of immunization of a live porcine reproductive and respiratory syndrome virus (PRRSV) vaccine in a heterologous virus challenge study. Vet. Res. 2016, 47, 45.
  115. Jeong, J.; Park, C.; Oh, T.; Park, K.H.; Yang, S.; Kang, I.; Park, S.-J.; Chae, C. Cross-protection of a modified-live porcine reproductive and respiratory syndrome virus (PRRSV)-2 vaccine against a heterologous PRRSV-1 challenge in late-term pregnancy gilts. Vet. Microbiol. 2018, 223, 119–125.
  116. Han, K.; Seo, H.W.; Park, C.; Chae, C. Vaccination of sows against type 2 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) before artificial insemination protects against type 2 PRRSV challenge but does not protect against type 1 PRRSV challenge in late gestation. Vet. Res. 2014, 45, 12.
  117. Yang, S.; Oh, T.; Cho, H.; Chae, C. A comparison of commercial modified-live PRRSV-1 and PRRSV-2 vaccines against a dual heterologous PRRSV-1 and PRRSV-2 challenge in late term pregnancy gilts. Comp. Immunol. Microbiol. Infect. Dis. 2020, 69, 101423.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
This entry is offline, you can click here to edit this entry!
ScholarVision Creations
Feedback