Comparative Measurement of Cell-Mediated Immune Responses of Swine to the M and N Proteins of Porcine Reproductive and Respiratory Syndrome Virus

Jeong, Hyun-Jeong; Song, Young-Suk; Lee, Sang‐Won; Lee, Joong‐Bok; Park, Seung‐Yong; Song, Chang‐Seon; Ha, Gun-Woo; Oh, Jeongseog; Oh, Youn-Kyoung; Choi, In‐Soo

doi:10.1128/cvi.00365-09

Cited by 28 publications

(17 citation statements)

References 46 publications

(62 reference statements)

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“…Despite differing MHC class-I and -II haplotypes, T-lymphocytes in gilt 1 and 2 recognized a common epitope-containing peptide (P538) in GP4. Identification of M protein sequences recognized by T-lymphocytes in several previous reports [58,59,62,68] as well as in the current study suggest that M protein is epitope-rich region suitable for inducing T-lymphocytes recognizing diverse PRRSV isolates, particularly since PBMCs have originated from genetically diverse pigs infected with various PRRSV genotypes.…”

Section: Discussionsupporting

confidence: 73%

Recognition of Highly Diverse Type-1 and -2 Porcine Reproductive and Respiratory Syndrome Viruses (PRRSVs) by T-Lymphocytes Induced in Pigs after Experimental Infection with a Type-2 PRRSV Strain

Chung

Cha

Grimm³

et al. 2016

PLoS ONE

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Background/AimLive attenuated vaccines confer partial protection in pigs before the appearance of neutralizing antibodies, suggesting the contribution of cell-mediated immunity (CMI). However, PRRSV-specific T-lymphocyte responses and protective mechanisms need to be further defined. To this end, the hypothesis was tested that PRRSV-specific T-lymphocytes induced by exposure to type-2 PRRSV can recognize diverse isolates.MethodsAn IFN-gamma ELISpot assay was used to enumerate PRRSV-specific T-lymphocytes from PRRSVSD23983-infected gilts and piglets born after in utero infection against 12 serologically and genetically distinct type-1 and -2 PRRSV isolates. The IFN-gamma ELISpot assay using synthetic peptides spanning all open reading frames of PRRSVSD23983 was utilized to localize epitopes recognized by T-lymphocytes. Virus neutralization tests were carried out using the challenge strain (type-2 PRRSVSD23983) and another strain (type-2 PRRSVVR2332) with high genetic similarity to evaluate cross-reactivity of neutralizing antibodies in gilts after PRRSVSD23983 infection.ResultsAt 72 days post infection, T-lymphocytes from one of three PRRSVSD23983-infected gilts recognized all 12 diverse PRRSV isolates, while T-lymphocytes from the other two gilts recognized all but one isolate. Furthermore, five of nine 14-day-old piglets infected in utero with PRRSVSD23983 had broadly reactive T-lymphocytes, including one piglet that recognized all 12 isolates. Overlapping peptides encompassing all open reading frames of PRRSVSD23983 were used to identify ≥28 peptides with T-lymphocyte epitopes from 10 viral proteins. This included one peptide from the M protein that was recognized by T-lymphocytes from all three gilts representing two completely mismatched MHC haplotypes. In contrast to the broadly reactive T-lymphocytes, neutralizing antibody responses were specific to the infecting PRRSVSD23983 isolate.ConclusionThese results demonstrated that T-lymphocytes recognizing antigenically and genetically diverse isolates were induced by infection with a type 2 PRRSV strain (SD23983). If these reponses have cytotoxic or other protective functions, they may help overcome the suboptimal heterologous protection conferred by conventional vaccines.

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Section: Discussionsupporting

confidence: 73%

Recognition of Highly Diverse Type-1 and -2 Porcine Reproductive and Respiratory Syndrome Viruses (PRRSVs) by T-Lymphocytes Induced in Pigs after Experimental Infection with a Type-2 PRRSV Strain

Chung

Cha

Grimm³

et al. 2016

PLoS ONE

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“…M protein is the most conserved structural protein among PRRSV strains (Kapur et al, 1996;Murtaugh et al, 1998) and it is the main inducer of virus-specific T-cell response (Bautista et al, 1999;Jeong et al, 2010). Our results indicated that M protein was fully stable in rTGEV (see above).…”

Section: Prrsv M Protein As Scaffold For Prrsv Antigenic Domains Exprsupporting

confidence: 55%

“…Neutralizing antibodies against PRRSV are mainly directed to GP5 protein (Kim and Yoon, 2008;Ostrowski et al, 2002), although neutralizing antibodies recognizing GP3 and GP4 have also been described following PRRSV infection (Costers et al, 2010;Oleksiewicz et al, 2002;Vanhee et al, 2011). PRRSV M protein is a potent inducer of T-cell proliferation in piglets infected with PRRSV, and may also play a role in protection (Bautista et al, 1999;Jeong et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Antigenic structures stably expressed by recombinant TGEV-derived vectors

et al. 2014

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Coronaviruses (CoVs) are positive-stranded RNA viruses with potential as immunization vectors, expressing high levels of heterologous genes and eliciting both secretory and systemic immune responses. Nevertheless, its high recombination rate may result in the loss of the full-length foreign gene, limiting their use as vectors. Transmissible gastroenteritis virus (TGEV) was engineered to express porcine reproductive and respiratory syndrome virus (PRRSV) small protein domains, as a strategy to improve heterologous gene stability. After serial passage in tissue cultures, stable expression of small PRRSV protein antigenic domains was achieved. Therefore, size reduction of the heterologous genes inserted in CoV-derived vectors led to the stable expression of antigenic domains. Immunization of piglets with these TGEV vectors led to partial protection against a challenge with a virulent PRRSV strain, as immunized animals showed reduced clinical signs and lung damage. Further improvement of TGEV-derived vectors will require the engineering of vectors with decreased recombination rate.

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“…T cell proliferation and IFN-␥ synthesis were induced in immunized pigs only in response to M and N, with M being more stimulatory. By contrast, serum antibodies were produced only to N (Jeong et al, 2010). This approach, using T cells and MHC-matched autologous APCs, to identify T cell epitopes is likely to be useful in future studies.…”

Section: Viral Epitope Targets Of T Cell Immunitymentioning

confidence: 99%

Innate and adaptive immunity against Porcine Reproductive and Respiratory Syndrome Virus

Loving

Osorio

Murtaugh

et al. 2015

Veterinary Immunology and Immunopathology

164

156

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Many highly effective vaccines have been produced against viruses whose virulent infection elicits strong and durable protective immunity. In these cases, characterization of immune effector mechanisms and identification of protective epitopes/immunogens has been informative for the development of successful vaccine programs. Diseases in which the immune system does not rapidly clear the acute infection and/or convalescent immunity does not provide highly effective protection against secondary challenge pose a major hurdle for clinicians and scientists. Porcine reproductive and respiratory syndrome virus (PRRSV) falls primarily into this category, though not entirely. PRRSV causes a prolonged infection, though the host eventually clears the virus. Neutralizing antibodies can provide passive protection when present prior to challenge, though infection can be controlled in the absence of detectable neutralizing antibodies. In addition, primed pigs (through natural exposure or vaccination with a modified-live vaccine) show some protection against secondary challenge. While peripheral PRRSV-specific T cell responses have been examined, their direct contribution to antibody-mediated immunity and viral clearance have not been fully elucidated. The innate immune response following PRRSV infection, particularly the antiviral type I interferon response, is meager, but when provided exogenously, IFN-α enhances PRRSV immunity and viral control. Overall, the quality of immunity induced by natural PRRSV infection is not ideal for informing vaccine development programs. The epitopes necessary for protection may be identified through natural exposure or modified-live vaccines and subsequently applied to vaccine delivery platforms to accelerate induction of protective immunity following vaccination. Collectively, further work to identify protective B and T cell epitopes and mechanisms by which PRRSV eludes innate immunity will enhance our ability to develop more effective methods to control and eliminate PRRS disease.

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Comparative Measurement of Cell-Mediated Immune Responses of Swine to the M and N Proteins of Porcine Reproductive and Respiratory Syndrome Virus

Cited by 28 publications

References 46 publications

Recognition of Highly Diverse Type-1 and -2 Porcine Reproductive and Respiratory Syndrome Viruses (PRRSVs) by T-Lymphocytes Induced in Pigs after Experimental Infection with a Type-2 PRRSV Strain

Recognition of Highly Diverse Type-1 and -2 Porcine Reproductive and Respiratory Syndrome Viruses (PRRSVs) by T-Lymphocytes Induced in Pigs after Experimental Infection with a Type-2 PRRSV Strain

Antigenic structures stably expressed by recombinant TGEV-derived vectors

Innate and adaptive immunity against Porcine Reproductive and Respiratory Syndrome Virus

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