title: HIV fragment gag vaccine induces broader T cell response in mice.
abstract: Broad T-cell response is considered critical for HIV-1 vaccines to compensate viral diversity. Usually, a limited number of immunodominant epitopes are recognized in natural infections, as well as in vaccinations. Here, we seek to overcome immunofocusing of CD8 T Cell responses to HIV-1 CN54 gag DNA (delivered as a plasmid) in BalB/C mice by splitting it into fragments for reducing competition of recognition between dominant and sub-dominant epitopes. As expected, mice immunized with mixture of DNA fragments elicited significantly broader T cell responses than whole-length gag. We also further studied the effects when fragments and full-length DNA vaccines are combined for prime-boost vaccination. Interestingly, mice primed with full-length gag and boosted with DNA vaccine fragments induced similar T-cell response breadth as mice both primed and boosted by fragments DNA. In contrast, mice primed with DNA vaccine fragments and boosted with full-length gag failed to broaden T cell responses, once again, only the dominant epitopes were recognized. In summary, our study demonstrated that "fragmentation strategy" can indeed broaden T cell responses. This enhancement is more likely achieved in boosting stage. This study offers a promising way to design a vaccine with higher chance covering the highly diversified circulating strains.
authors.affiliation: Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Liu
authors.forename: Fusheng
authors.initials: F
authors.lastname: Li
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.forename: Kunxue
authors.initials: K
authors.lastname: Hong
authors.forename: Xin
authors.initials: X
authors.lastname: Meng
authors.forename: Jianping
authors.initials: J
authors.lastname: Chen
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhang
authors.forename: Zhu
authors.initials: Z
authors.lastname: Huo
authors.forename: Maosheng
authors.initials: M
authors.lastname: Sun
authors.forename: Steven G
authors.initials: SG
authors.lastname: Self
authors.forename: Yiming
authors.initials: Y
authors.lastname: Shao
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D007117:Immunization, Secondary / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination / Q000379:methods; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D000939:Epitopes; D019444:Vaccines, DNA; D054301:gag Gene Products, Human Immunodeficiency Virus