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A recombinant multi-epitope protein MEP1 elicits efficient long-term immune responses against HIV-1 infection.

ABSTRACT: The effective protective HIV vaccine should elicit either protective antibodies or effective T cell response, or both. To improve the efficacy of HIV-1 vaccines, HLA polymorphism and HIV-1 diversity are 2 key factors to be considered for vaccine development. In this study, we expressed a recombinant multi-epitope protein MEP1 which has the same amino acid sequence as a DNA vaccine for Chinese population in our previous report. We found that MEP1 alone could elicit moderate levels of humoral and cellular immune responses, but these responses could not provide protection from challenge with a recombinant virus rTTV-lucgag, which expresses Gag of HIV-1 CRF_07BC. Nevertheless, when MEP1 was immunized with aluminum adjuvant, both humoral and cellular immune responses were significantly increased, and they were protective against virus infection; meanwhile, MEP1 with aluminum not only elicited early (10 d post immunization) but also a long-term (at least 44 weeks post immunization) immune responses in BALB/c mice. These results suggested that MEP1 has the potential to be developed as an effective vaccine candidate, and that suitable adjuvant is necessary for this protein to generate protective immune responses.

SUBMITTER: Yang Y

PROVIDER: S-EPMC5489306 | biostudies-other | 2017 Jun

REPOSITORIES: biostudies-other

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A recombinant multi-epitope protein MEP1 elicits efficient long-term immune responses against HIV-1 infection.

Yang Yi Y Zhu Qing Q Sun Weilai W Guo Jingjing J Ning Xiuzhe X Li Qiao Q Guo Yan Y Li Junfeng J Kou Zhihua Z Zhou Yusen Y

Human vaccines & immunotherapeutics 20170216 6

The effective protective HIV vaccine should elicit either protective antibodies or effective T cell response, or both. To improve the efficacy of HIV-1 vaccines, HLA polymorphism and HIV-1 diversity are 2 key factors to be considered for vaccine development. In this study, we expressed a recombinant multi-epitope protein MEP1 which has the same amino acid sequence as a DNA vaccine for Chinese population in our previous report. We found that MEP1 alone could elicit moderate levels of humoral and ...[more]

PMID: 28281860

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Project description:BackgroundInfluenza A virus is one of the leading causes of annual mortality. The emerging of novel escape variants of the influenza A virus is still a considerable challenge in the annual process of vaccine production. The evolution of vaccines ranks among the most critical successes in medicine and has eradicated numerous infectious diseases. Recently, multi-epitope vaccines, which are based on the selection of epitopes, have been increasingly investigated.ResultsThis study utilized an immunoinformatic approach to design a recombinant multi-epitope vaccine based on a highly conserved epitope of hemagglutinin, neuraminidase, and membrane matrix proteins with fewer changes or mutate over time. The potential B cells, cytotoxic T lymphocytes (CTL), and CD4 T cell epitopes were identified. The recombinant multi-epitope vaccine was designed using specific linkers and a proper adjuvant. Moreover, some bioinformatics online servers and datasets were used to evaluate the immunogenicity and chemical properties of selected epitopes. In addition, Universal Immune System Simulator (UISS) in silico trial computational framework was run after influenza exposure and recombinant multi-epitope vaccine administration, showing a good immune response in terms of immunoglobulins of class G (IgG), T Helper 1 cells (TH1), epithelial cells (EP) and interferon gamma (IFN-g) levels. Furthermore, after a reverse translation (i.e., convertion of amino acid sequence to nucleotide one) and codon optimization phase, the optimized sequence was placed between the two EcoRV/MscI restriction sites in the PET32a+ vector.ConclusionsThe proposed "Recombinant multi-epitope vaccine" was predicted with unique and acceptable immunological properties. This recombinant multi-epitope vaccine can be successfully expressed in the prokaryotic system and accepted for immunogenicity studies against the influenza virus at the in silico level. The multi-epitope vaccine was then tested with the Universal Immune System Simulator (UISS) in silico trial platform. It revealed slight immune protection against the influenza virus, shedding the light that a multistep bioinformatics approach including molecular and cellular level is mandatory to avoid inappropriate vaccine efficacy predictions.

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A recombinant multi-epitope protein MEP1 elicits efficient long-term immune responses against HIV-1 infection.

Publications

A recombinant multi-epitope protein MEP1 elicits efficient long-term immune responses against HIV-1 infection.

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