Replacing the decoy epitope of PCV2b capsid protein with a protective epitope enhances efficacy of PCV2b vaccine

Yu, Chih-Chia; Li, Xin; Liu, Jiwei; Diao, Wenzhen; Zhang, Leichao; Xiao, Yuxiu; Wei, Hongfei; Yu, Yongli; Yu, Yaqin; Wang, Liying

doi:10.1016/j.vaccine.2016.10.044

Cited by 15 publications

(9 citation statements)

References 25 publications

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“…It was shown elsewhere that a natural immunodominant decoy epitope on the PCV‐2 CP subunits presents to the host immune system during CP expression and subsequent protein folding in the animal host cells, allowing the virus to partially evade the host's immune response during virion formation (Trible et al ., ). Mature purified PCV‐2 VLPs will have this decoy epitope embedded in the particle, however, and will display a ‘finished’ virion structure so that specific protective humoural and cellular immune responses will be generated in the host without any decoy effect (Yu et al ., ). Viral CPs self‐assembling into VLPs also have the added potential to be used as display vectors to carry multimeric epitopes against different strains of the same virus (Crisci et al ., ).…”

Section: Discussionmentioning

confidence: 97%

Immunogenicity of plant‐produced porcine circovirus‐like particles in mice

Gunter

Regnard

Rybicki

et al. 2019

Plant Biotechnology Journal

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Summary Porcine circovirus type 2 ( PCV ‐2) is the main causative agent associated with a group of diseases collectively known as porcine circovirus‐associated disease ( PCAD ). There is a significant economic strain on the global swine industry due to PCAD and the production of commercial PCV ‐2 vaccines is expensive. Plant expression systems are increasingly regarded as a viable technology to produce recombinant proteins for use as pharmaceutical agents and vaccines. However, successful production and purification of PCV ‐2 capsid protein ( CP ) from plants is an essential first step towards the goal of a plant‐produced PCV ‐2 vaccine candidate. In this study, the PCV ‐2 CP was transiently expressed in Nicotiana benthamiana plants via agroinfiltration and PCV ‐2 CP was successfully purified using sucrose gradient ultracentrifugation. The CP self‐assembled into virus‐like particles ( VLP s) resembling native virions and up to 6.5 mg of VLP s could be purified from 1 kg of leaf wet weight. Mice immunized with the plant‐produced PCV ‐2 VLP s elicited specific antibody responses to PCV ‐2 CP . This is the first report describing the expression of PCV ‐2 CP in plants, the confirmation of its assembly into VLP s and the demonstration of their use to elicit a strong immune response in a mammalian model.

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Section: Discussionmentioning

confidence: 97%

Immunogenicity of plant‐produced porcine circovirus‐like particles in mice

Gunter

Regnard

Rybicki

et al. 2019

Plant Biotechnology Journal

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“…Recently, decoy epitopes were described for the porcine circovirus and the antibody response to such epitopes was shown to impair vaccine efficacy [ 33 ]. Replacing the decoy epitope with a protective epitope was shown to enhance vaccine efficacy [ 34 ]. This could not be applied to SU5, which is masked in the context of infectious viral particles.…”

Section: Discussionmentioning

confidence: 99%

An Immunodominant Region of the Envelope Glycoprotein of Small Ruminant Lentiviruses May Function as Decoy Antigen

Zahno¹,

Bertoni²

2018

Viruses

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(1) Background: Small ruminant lentiviruses (SRLV) persist in infected goats that mount a strong humoral immune response characterized by low neutralizing titers. In this study, we characterized the antibody response to SU5, a variable, immunodominant epitope of the envelope glycoprotein of SRLV. We tested the working hypothesis that the variability of SU5 reflects escape from neutralizing antibody. (2) Methods: Affinity purified anti-SU5 antibody were tested for their neutralizing activity to the homologous lentivirus. Virus culture supernatant—in native form or following sonication and filtration—was used to test the ability of free envelope glycoproteins to compete for binding in a SU5-peptide-ELISA. (3) Results: Anti-SU5 antibodies are not neutralizing, strongly suggesting that they do not bind intact viral particles. In contrast, shed envelope glycoproteins efficiently compete for binding in a SU5-ELISA, providing convincing evidence that the SU5 epitope is exposed only on shed envelope glycoproteins. (4) Conclusions: Our results show that the antibody engaging SU5 is not neutralizing and does not appear to bind to SU expressed at the surface of virus particles. We propose that SU5 is a potential decoy epitope exposed on shaded envelope glycoproteins, luring the humoral immune response in committing an original antigenic sin to a functionally irrelevant epitope.

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“…To further examine whether TIO1 or TIO3 could act as an adjuvant by inhibiting TGF‐β2 expression, we first evaluated the adjuvanticity of TIOs to recombinant protein vaccines. The Cp vaccines were prepared by formulating Cp (a recombinant PCV2b capsid protein expressed in E. coli ), 34 at 5 µg/shot, with ISA35 (an oil‐in‐water emulsion from Seppic, Paris, France), 35 with or without TIOs or cODN, at 10 µg/shot. To test the feasibility of the TIOs to the inactivated virus vaccines, the inactivated IAV in ISA35 emulsion (iIAV) vaccines were prepared by formulating iIAV, at 0.5 µg/shot, with ISA35, with or without TIOs or cODN, at 10 µg/shot.…”

Section: Methodsmentioning

confidence: 99%

TGF-β2 interfering oligonucleotides used as adjuvants for microbial vaccines

Sun

Yang

et al. 2020

Journal of Leukocyte Biology

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The success of using immune checkpoint inhibitors to treat cancers implies that inhibiting an immunosuppressive cytokine, such as TGF-2, could be a strategy to develop novel adjuvants for microbial vaccines. To develop nucleic acid based TGF-2 inhibitors, we designed three antisense oligonucleotides, designated as TIO1, TIO2, and TIO3, targeting the conserve regions identical in human and mouse TGF-2 mRNA 3 ′-untranslated region. In cultured immune cells, TIO3 and TIO1 significantly reduced the TGF-2 mRNA expression and protein production. In mice, the TIO3 and TIO1, when formulated in various microbial vaccines, significantly enhanced the antibody response to the vaccines, and the TIO3-adjuvanted influenza virus vaccine induced effective protection against the influenza virus challenge. In the immunized mice, TIO3 formulated in microbial vaccines dramatically reduced surface-bound TGF-2 expression on CD4 + T cells and CD19 + B cells in the lymph node (LN) cells and spleen cells; up-regulated the expression of CD40, CD80, CD86, and MHC II molecules on CD19 + B cells and CD11c + dendritic cells; and promoted IFNproduction in CD4 + T cells and CD8 + T cells in the LN cells. Overall, TIO3 or TIO1 could be used as a novel type of adjuvant for facilitating the microbial vaccines to elicit more vigorous and persistent antibody response by interfering with TGF-2 expression.

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Replacing the decoy epitope of PCV2b capsid protein with a protective epitope enhances efficacy of PCV2b vaccine

Cited by 15 publications

References 25 publications

Immunogenicity of plant‐produced porcine circovirus‐like particles in mice

Immunogenicity of plant‐produced porcine circovirus‐like particles in mice

An Immunodominant Region of the Envelope Glycoprotein of Small Ruminant Lentiviruses May Function as Decoy Antigen

TGF-β2 interfering oligonucleotides used as adjuvants for microbial vaccines

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