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To induce multi\u2010functional T response against multi\u2010TB antigens, a multi\u2010epitope DNA vaccine and a \u2018protein backbone grafting\u2019 design method is adopted to graft five discontinuous T\u2010cell epitopes into HSP65 scaffold protein of\n                      <jats:italic>M. tb<\/jats:italic>\n                      for enhancement of epitope processing and immune presentation. A DNA plasmid with five T\u2010cell epitopes derived from ESAT\u20106, Ag85B, MTB10.4, PPE25 and PE19 proteins of H37Rv strain of\n                      <jats:italic>M. tb<\/jats:italic>\n                      genetically inserted into HSP65 backbone was constructed and designated as pPES. After confirmation of its\n                      <jats:italic>in vitro<\/jats:italic>\n                      expression efficiency, pPES DNA was i.m. injected into C57BL\/6 mice with four doses of 50\u2009\u00b5g DNA followed by mycobacterial challenge 4 weeks after the final immunization. It was found that pPES DNA injection maintained the ability of HSP65 backbone to induce specific serum IgG. ELISPOT assay demonstrated that pPES epitope\u2010scaffold construct was significantly more potent to induce IFN\u2010\u03b3\n                      <jats:sup>+<\/jats:sup>\n                      T response to five T\u2010cell epitope proteins than other DNA constructs (with epitopes alone or with epitope series connected to HSP65), especially in multi\u2010functional\u2010CD4\n                      <jats:sup>+<\/jats:sup>\n                      T response. It also enhanced granzyme B\n                      <jats:sup>+<\/jats:sup>\n                      CTL and IL\u20102\n                      <jats:sup>+<\/jats:sup>\n                      CD8\n                      <jats:sup>+<\/jats:sup>\n                      T response. Furthermore, significantly improved protection against\n                      <jats:italic>Mycobacterium bovis<\/jats:italic>\n                      BCG challenge was achieved by pPES injection compared to other DNA constructs. Taken together, HSP65 scaffold grafting strategy for multi\u2010epitope DNA vaccine represents a successful example of rational protein backbone engineering design and could prove useful in TB vaccine design.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/1348-0421.12410","type":"journal-article","created":{"date-parts":[[2016,8,17]],"date-time":"2016-08-17T01:12:48Z","timestamp":1471396368000},"page":"634-645","source":"Crossref","is-referenced-by-count":21,"title":["DNA vaccine with discontinuous T\u2010cell epitope insertions into HSP65 scaffold as a potential means to improve immunogenicity of multi\u2010epitope\n                    <i>Mycobacterium tuberculosis<\/i>\n                    vaccine"],"prefix":"10.1111","volume":"60","author":[{"given":"Manli","family":"Wu","sequence":"first","affiliation":[{"name":"Institute of Biology and Medical Sciences Soochow University Building 703, 199 Ren\u2010ai Road Suzhou 215123 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