A peptide vaccine based on a B-cell epitope on the VP1 protein of enterovirus 70 induces a strong antibody response

Park, Kee-Bum; Lim, Byung-Kwan; Ye, Michael B.; Chung, Sooyoung E.; Nam, Jae‐Hwan

doi:10.4149/av_2012_04_337

Cited by 7 publications

(9 citation statements)

References 11 publications

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“…A possible explanation for the high immunogenicity of a sequence that is inside the capsid is the dynamic motions of virions referred to as “capsid breathing.” Even residues that are located on the inside of the capsid can be temporarily exposed on the virion surface and may be accessible to antibodies. Similar targeting of internal peptides by antibodies has been described in other picornaviruses ( 73 , 74 ). In poliovirus type 1, antibodies can bind to residues 34 to 53 of VP1 located on the interior of the particle ( Fig.…”

Section: Resultssupporting

confidence: 72%

The Structure of Human Parechovirus 1 Reveals an Association of the RNA Genome with the Capsid

Kalynych

Pálková

Plevka

2016

J Virol

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Parechoviruses are human pathogens that cause diseases ranging from gastrointestinal disorders to encephalitis. Unlike those of most picornaviruses, parechovirus capsids are composed of only three subunits: VP0, VP1, and VP3. Here, we present the structure of a human parechovirus 1 (HPeV-1) virion determined to a resolution of 3.1 Å. We found that interactions among pentamers in the HPeV-1 capsid are mediated by the N termini of VP0s, which correspond to the capsid protein VP4 and the N-terminal part of the capsid protein VP2 of other picornaviruses. In order to facilitate delivery of the virus genome into the cytoplasm, the N termini of VP0s have to be released from contacts between pentamers and exposed at the particle surface, resulting in capsid disruption. A hydrophobic pocket, which can be targeted by capsid-binding antiviral compounds in many other picornaviruses, is not present in HPeV-1. However, we found that interactions between the HPeV-1 single-stranded RNA genome and subunits VP1 and VP3 in the virion impose a partial icosahedral ordering on the genome. The residues involved in RNA binding are conserved among all parechoviruses, suggesting a putative role of the genome in virion stability or assembly. Therefore, putative small molecules that could disrupt HPeV RNA-capsid protein interactions could be developed into antiviral inhibitors.IMPORTANCE Human parechoviruses (HPeVs) are pathogens that cause diseases ranging from respiratory and gastrointestinal disorders to encephalitis. Recently, there have been outbreaks of HPeV infections in Western Europe and North America. We present the first atomic structure of parechovirus HPeV-1 determined by X-ray crystallography. The structure explains why HPeVs cannot be targeted by antiviral compounds that are effective against other picornaviruses. Furthermore, we found that the interactions of the HPeV-1 genome with the capsid resulted in a partial icosahedral ordering of the genome. The residues involved in RNA binding are conserved among all parechoviruses, suggesting an evolutionarily fixed role of the genome in virion assembly. Therefore, putative small molecules disrupting HPeV RNA-capsid protein interactions could be developed into antiviral inhibitors.

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Section: Resultssupporting

confidence: 72%

The Structure of Human Parechovirus 1 Reveals an Association of the RNA Genome with the Capsid

Kalynych

Pálková

Plevka

2016

J Virol

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“…The HPeV3 VP1 C-terminus, which according to the structure is disordered but exposed on the surface 28 , may therefore contain antigenic sites of HPeV3. However, buried residues not exposed on the surface may also have a role in antigenicity via capsid breathing, as has been shown for an immunogenic epitope in the PV and enterovirus 70 VP1 protein 35 , 36 .…”

Section: Discussionmentioning

confidence: 94%

Strain-dependent neutralization reveals antigenic variation of human parechovirus 3

Karelehto

Sanden

Geraets

et al. 2017

Sci Rep

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Human parechovirus 3 (HPeV3), a member of the Picornavirus family, is frequently detected worldwide. However, the observed seropositivity rates for HPeV3 neutralizing antibodies (nAbs) vary from high in Japan to low in the Netherlands and Finland. To study if this can be explained by technical differences or antigenic diversity among HPeV3 strains included in the serological studies, we determined the neutralizing activity of Japanese and Dutch intravenous immunoglobulin batches (IVIG), a rabbit HPeV3 hyperimmune polyclonal serum, and a human HPeV3-specific monoclonal antibody (mAb) AT12-015, against the HPeV3 A308/99 prototype strain and clinical isolates from Japan, the Netherlands and Australia, collected between 1989 and 2015. The rabbit antiserum neutralized all HPeV3 isolates whereas the neutralization capacity of the IVIG batches varied, and the mAb exclusively neutralized the A308/99 strain. Mapping of the amino acid variation among a subset of the HPeV3 strains on an HPeV3 capsid structure revealed that the majority of the surface-exposed amino acid variation was located in the VP1. Furthermore, amino acid mutations in a mAb AT12-015-resistant HPeV3 A308/99 variant indicated the location for potential antigenic determinants. Virus aggregation and the observed antigenic diversity in HPeV3 can explain the varying levels of nAb seropositivity reported in previous studies.

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“…Autoantigen epitope vaccines present as a better treatment modality for autoimmune disease. Due to their low molecular weight and unitary structure, self-antigens reduce immunogenicity and cannot induce the desired immune responses, particularly in B-cell epitope-mediated humoral immune responses (16). To solve this problem, short peptide vaccine epitope and carrier protein crosslinking methods were used to improve immunogenicity.…”

Section: Discussionmentioning

confidence: 99%

Prediction and identification of B-cell epitopes for tumor necrosis factor-α

Zhang

Cui

et al. 2017

Molecular Medicine Reports

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The aim of the present study was to predict and identify B‑cell epitopes for mouse tumor necrosis factor‑α (mTNF‑α). DNAStar and BcePred software were used to predict B‑cell epitopes for mTNF‑α. A predicted eight‑branch multiple antigenic polypeptide (MAP) was synthesized and used to immunize BALB/c mice, combined with a promiscuous helper interleukin‑1β epitope (VQGEESNDK, amino acids 163‑171). The serum titer was measured. The specificity and avidity were determined by western blotting and indirect enzyme‑linked immunosorbent assay (ELISA). Amino acids 54‑65 (MAP1) and 78‑92 (MAP2) of mTNF‑α were predicted as most likely to be B‑cell epitopes. Dynamic monitoring of antibody concentration demonstrated that MAP1 and MAP2 may induce the production of specific antibodies with a higher antibody level for MAP2. Furthermore, MAP1 and MAP2 were confirmed to induce mTNF‑α‑specific antibodies by western blotting. Indirect ELISA was used to confirm that MAP2 had the highest affinity with commercial anti‑mTNF‑α antibody. Amino acids 54‑65 and 78‑94 of mTNF‑α are B‑cell epitopes, wherein amino acids 78‑94 have the strongest immunogenicity. The present study provides a theoretical basis for further research into the mTNF‑α polypeptide antibody and a B‑cell MAP vaccine.

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A peptide vaccine based on a B-cell epitope on the VP1 protein of enterovirus 70 induces a strong antibody response

Cited by 7 publications

References 11 publications

The Structure of Human Parechovirus 1 Reveals an Association of the RNA Genome with the Capsid

The Structure of Human Parechovirus 1 Reveals an Association of the RNA Genome with the Capsid

Strain-dependent neutralization reveals antigenic variation of human parechovirus 3

Prediction and identification of B-cell epitopes for tumor necrosis factor-α

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