An ingenious design for peptide vaccines

Yano, Akira; Onozuka, Atsuko; Asahi-Ozaki, Yasuko; Imai, Shoichi; Hanada, Nobuhiro; Miwa, Yoshikatsu; Nisizawa, Tosiki

doi:10.1016/j.vaccine.2005.01.031

Cited by 77 publications

(46 citation statements)

References 13 publications

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“…KK is an important proteasome for MHC-II-restricted antigen processing [38], and Livingston et al [39] designed a universal spacer GPGPG. In this study, 6 B-cell epitopes, 4 CTL epitopes and 2 Th epitopes were predicted and connected in series as an MEP.…”

Section: Discussionmentioning

confidence: 99%

“…To our knowledge, our study is the first report of tandem assembling of a B, CTL and Th MEP for hMPV. GPGPG and KK residues were introduced as a spacer between adjacent epitopes, which not only minimized junctional epitopes, but also simultaneously augmented proteasome processing, whilst also increasing the immunogenicity [38]. The designed mep gene was expressed in E. coli .…”

Section: Discussionmentioning

confidence: 99%

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Design and Evaluation of a Multi-Epitope Peptide of Human Metapneumovirus

Guo

Kong

et al. 2015

Intervirology

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Objectives: No licensed vaccines or therapeutic agents for human metapneumovirus (hMPV) infection exist to date. We aimed to construct a multi-epitope peptide (MEP) of hMPV to show promising results for epitope-based vaccine development. Methods: Six independent algorithms were screened to predict B-cell epitopes of hMPV, and three algorithms were used to predict cytotoxic T lymphocyte and T helper (Th) lymphocyte epitopes. Predicted epitopes were assembled in series with the spacers GPGPG and KK introduced, termed MEP. Recombinant mep genes were inserted into pET32a(+) plasmid and expressed in Escherichia coli strain BL21 (DE3). BALB/c mice were immunized with MEP with different adjuvants. Antibody titer, lymphocyte proliferation, cytotoxic T lymphocyte (CTL) activity and splenocyte cytokines were detected 2 weeks later after the last immunization. Microneutralization assay was used to detect neutralizing antibodies. Results: Six B-cell epitopes, four CTL epitopes and two Th epitopes were screened to construct the mep gene. Expressed MEP induced >10⁴ antibodies in BALB/c mice, and produced anti-MEP antibody reacting with hMPV strains specifically as detected in indirect fluorescent assay (the titer was 160). The lymphocyte proliferation index, CTL activity and splenocyte cytokines of the MEP immunization groups were higher than in the control group (p < 0.05). Both IgG1 and IgG2a antibodies could be detected in the different groups, and balanced Th1/Th2 cytokines were secreted by splenocytes in these groups. The mean neutralizing titers of the MEP+CpG ODN, MEP+Alum and MEP+Alum+ CpG ODN groups were 87 (95% CI 50-126), 93 (95% CI 67-121) and 96 (95% CI 69-147), respectively. Conclusion: MEP of hMPV elicited both strong humoral immunity and cell-mediated immunity in mice. The anti-MEP serum could neutralize hMPV infection in vitro. Joint use of CpG ODN and aluminum hydroxide adjuvants obtained the best immune effects. This study may contribute to hMPV epitope-based vaccine development.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Design and Evaluation of a Multi-Epitope Peptide of Human Metapneumovirus

Guo

Kong

et al. 2015

Intervirology

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“…The "KK" linker was also added to prevent the epitopes between subtypes from "splitting", that is, to avoid generation of new junctional epitopes [16,17]. Based on the design of the epitope box, the nucleotide sequences were codon-optimized and the peptides synthesized accordingly (Xu Guan Biological Engineering Co., Ltd. Shanghai, PR China).…”

Section: Methodsmentioning

confidence: 99%

Protection against H1N1 influenza challenge by a DNA vaccine expressing H3/H1 subtype hemagglutinin combined with MHC class II-restricted epitopes

Tan

Zhang

et al. 2010

Virol J

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BackgroundMultiple subtypes of avian influenza viruses have crossed the species barrier to infect humans and have the potential to cause a pandemic. Therefore, new influenza vaccines to prevent the co-existence of multiple subtypes within a host and cross-species transmission of influenza are urgently needed.MethodsHere we report a multi-epitope DNA vaccine targeted towards multiple subtypes of the influenza virus. The protective hemagglutinin (HA) antigens from H5/H7/H9 subtypes were screened for MHC II class-restricted epitopes overlapping with predicted B cell epitopes. We then constructed a DNA plasmid vaccine, pV-H3-EHA-H1, based on HA antigens from human influenza H3/H1 subtypes combined with the H5/H7/H9 subtype Th/B epitope box.ResultsEpitope-specific IFN-γ ELISpot responses were significantly higher in the multi-epitope DNA group than in other vaccine and control groups (P < 0.05). The multi-epitope group significantly enhanced Th2 cell responses as determined by cytokine assays. The survival rate of mice given the multi-epitope vaccine was the highest among the vaccine groups, but it was not significantly different compared to those given single antigen expressing pV-H1HA1 vaccine and dual antigen expressing pV-H3-H1 vaccine (P > 0.05). No measurable virus titers were detected in the lungs of the multi-epitope immunized group. The unique multi-epitope DNA vaccine enhanced virus-specific antibody and cellular immunity as well as conferred complete protection against lethal challenge with A/New Caledonia/20/99 (H1N1) influenza strain in mice.ConclusionsThis approach may be a promising strategy for developing a universal influenza vaccine to prevent multiple subtypes of influenza virus and to induce long-term protective immune against cross-species transmission.

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“…EP67 directs the EBV to complement receptors and, although not yet tested, may further enhance Th17 immunity. CD4 + and CD8 + multiepitope vaccines are constructed using nonimmunogenic GPGPG or di-lysine (KK) linkers [25], [26]. β-1,3-glucans and opsonic C3 deposited on the surface of GPs bind to Dectin-1 and complement receptors (CR), respectively, and induce phagocytosis by APCs (MΦ and DC) followed by antigen processing and peptide epitope display as MHC I or II complexes [17], [19].…”

Section: A Novel Adjuvant Enhances Cellular Immunity Induced By a LIVmentioning

confidence: 99%