Broad neutralization activity against both PRRSV-1 and PRRSV-2 and enhancement of cell mediated immunity against PRRSV by a novel IgM monoclonal antibody

Wu, Chunyan; Gu, Guoqian; Zhai, Tianshu; Wang, Yajing; Yang, Yongling; Li, Yafei; Xu, Zheng; Zhao, Qin; Nan, Yuchen

doi:10.1016/j.antiviral.2020.104716

Cited by 14 publications

(17 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Multiple neutralizing epitopes have been identified among PRRSV major and minor envelope proteins. Several studies showed that minor glycoproteins GP2, GP3 and GP4 of PRRSV1 strains possess neutralizing epitopes, while GP5 and M heterodimers of PRRSV2 strains are the major target for viral neutralization [ 15 , 51 ]. PRRSV infection might induce homologous nAbs, heterologous nAbs and bnAbs [ 13 , 17 ].…”

Section: Discussionmentioning

confidence: 99%

“…Even though protection efficiency is a vital criterion for breeding next generation PRRS vaccines, safety is another major concern that is at least as important as protection efficiency. Persistent MLV infection in vaccinated pigs and transmission of vaccine strains to naïve pigs have been confirmed [ 27 , 51 , 61 ]. In addition, MLV-derived field isolates and recombinants from MLV and wild-type strains have been isolated [ 26 , 62 ].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Chimeric HP-PRRSV2 containing an ORF2-6 consensus sequence induces antibodies with broadly neutralizing activity and confers cross protection against virulent NADC30-like isolate

Chen

Tian

et al. 2021

Vet Res

View full text Add to dashboard Cite

Due to the substantial genetic diversity of porcine reproductive and respiratory syndrome virus (PRRSV), commercial PRRS vaccines fail to provide sufficient cross protection. Previous studies have confirmed the existence of PRRSV broadly neutralizing antibodies (bnAbs). However, bnAbs are rarely induced by either natural infection or vaccination. In this study, we designed and synthesized a consensus sequence of PRRSV2 ORF2-6 genes (ORF2-6-CON) encoding all envelope proteins based on 30 representative Chinese PRRSV isolates. The ORF2-6-CON sequence shared > 90% nucleotide identities to all four lineages of PRRSV2 isolates in China. A chimeric virus (rJS-ORF2-6-CON) containing the ORF2-6-CON was generated using the avirulent HP-PRRSV2 JSTZ1712-12 infectious clone as a backbone. The rJS-ORF2-6-CON has similar replication efficiency as the backbone virus in vitro. Furthermore, pig inoculation and challenge studies showed that rJS-ORF2-6-CON is not pathogenic to piglets and confers better cross protection against the virulent NADC30-like isolate than a commercial HP-PRRS modified live virus (MLV) vaccine. Noticeably, the rJS-ORF2-6-CON strain could induce bnAbs while the MLV strain only induced homologous nAbs. In addition, the lineages of VDJ repertoires potentially associated with distinct nAbs were also characterized. Overall, our results demonstrate that rJS-ORF2-6-CON is a promising candidate for the development of a PRRS genetic engineered vaccine conferring cross protection.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Chimeric HP-PRRSV2 containing an ORF2-6 consensus sequence induces antibodies with broadly neutralizing activity and confers cross protection against virulent NADC30-like isolate

Chen

Tian

et al. 2021

Vet Res

View full text Add to dashboard Cite

show abstract

“…Purification of PRRSV SD16 virions from cell culture media obtained from PRRSV-infected MARC-145 cells was performed as previously described (67). Preparation of mouse serum against inactivated PRRSV virions was previously described (68). Serum samples of immunized mice were evaluated by using the Idexx PRRS X3 enzyme-linked immunosorbent assay (ELISA) kit by replacing the original horseradish peroxidase (HRP)-labeled anti-swine antibodies with HRP-labeled anti-mouse IgG (Thermo Fisher Scientific) in order to determine the serum conversion as previously described (68).…”

Section: Methodsmentioning

confidence: 99%

Porcine Reproductive and Respiratory Syndrome Virus Promotes SLA-DR-Mediated Antigen Presentation of Nonstructural Proteins To Evoke a Nonneutralizing Antibody Response In Vivo

Shi

Yang

et al. 2020

J Virol

Self Cite

View full text Add to dashboard Cite

The humoral immune response against PRRSV infection is characterized by a rapid induction of non-neutralizing antibodies (NAbs) against non-structure proteins (NSPs). Here, we systematically investigated the potential mechanism for the induction of PRRSV NSP-specific non-NAbs. Our data suggested that PRRSV-NSP-specific NAbs appeared within 10 days after PRRSV infection in vivo. In the in vitro model, functional upregulation of the SLA-DR was observed in bone marrow-derived dendritic cells (BM-DCs) and porcine alveolar macrophages (PAMs), whereas remarkable inhibition at the mRNA level was observed after infection by both PRRSV-1 and PRRSV-2 isolates. Notably, the inconsistency in SLA-DR expression between the mRNA and protein levels was resulted from the de-ubiquitination of SLA-DR via the OTU domain of PRRSV-NSP2 to inhibit ubiquitin-mediated degradation. Moreover, mass spectrometry-based immunopeptidome analysis identified immunopeptides originating from multiple PRRSV-NSPs within SLA-DR of PRRSV-infected BM-DCs. Meanwhile, these PRRSV-NSP-derived immunopeptides could be specifically recognized by serum from PRRSV-infected piglets. Notably, certain NSP-derived immunopeptides characterized in vitro could be identified from PAMs or hilar lymph nodes from PRRSV-infected piglets. More importantly, in vitro neutralizing assay indicated that serum antibodies against NSP-immunopeptides were unbale to neutralize PRRSV in vitro. Conversely, certain Structure Proteins (SPs)-derived immunopeptides were identified and could be recognize by pig hyperimmune serum against PRRSV, further indicates that NSP-derived antibodies response is non-protective in vivo. In conclusion, our data suggested that PRRSV infection interferes with the MHC-II molecule-mediated antigen presentation in APCs via promoting SLA-DR expression to present immunopeptides from PRRSV-NSPs, which contributes to the induction of non-NAbs antibodies in vivo. IMPORTANCE PRRSV has haunted the swine industry for over 30 years since its emergence. Besides the limited efficacy of PRRSV Modified live vaccines (MLV) against heterogeneous PRRSV isolate, rapid induction of non-neutralizing antibodies (non-NAbs) against PRRSV-NSPs after MLV immunization or wild strains infection was one of the reasons hampered development of an effective vaccine. By using in vitro generated BM-DCs as models to understand the antigen presentation process of PRRSV and, our data indicated that PRRSV infection of BM-DCs promotes functional SLA-DR upregulation to present PRRRSV-NSPs- derived immunopeptides for evoking non-NAbs response in vivo. Our work not only uncovered novel mechanism regarding interference of host antigen presentation by PRRSV but also revealed novel insight for understanding the rapid production of non-neutralizing antibodies against PRRSV-NSPs, which may benefit for developing an effective PRRSV vaccine against PRRSV in future.

show abstract

“…These envelope proteins would be candidates for vaccine antigens that can induce broadly neutralizing antibodies, which may be of significance in cross-protection. A recent study reports that a broadly neutralizing monoclonal antibody appears to recognize a specific virus epitope that requires post-translational modification within the host cellular Golgi apparatus [ 95 ]. It suggests the existence of a novel epitope that can confer cross-protection.…”

Section: Aberrant Immune Responses Induced By Prrsvmentioning

confidence: 99%

Porcine Reproductive and Respiratory Syndrome Virus: Immune Escape and Application of Reverse Genetics in Attenuated Live Vaccine Development

Wang

Feng

2021

Vaccines

View full text Add to dashboard Cite

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.

show abstract

Broad neutralization activity against both PRRSV-1 and PRRSV-2 and enhancement of cell mediated immunity against PRRSV by a novel IgM monoclonal antibody

Cited by 14 publications

References 51 publications

Chimeric HP-PRRSV2 containing an ORF2-6 consensus sequence induces antibodies with broadly neutralizing activity and confers cross protection against virulent NADC30-like isolate

Chimeric HP-PRRSV2 containing an ORF2-6 consensus sequence induces antibodies with broadly neutralizing activity and confers cross protection against virulent NADC30-like isolate

Porcine Reproductive and Respiratory Syndrome Virus Promotes SLA-DR-Mediated Antigen Presentation of Nonstructural Proteins To Evoke a Nonneutralizing Antibody Response In Vivo

Porcine Reproductive and Respiratory Syndrome Virus: Immune Escape and Application of Reverse Genetics in Attenuated Live Vaccine Development

Contact Info

Product

Resources

About