title: In silico design of a DNA-based HIV-1 multi-epitope vaccine for Chinese populations.
abstract: The development of an HIV-1 vaccine that is capable of inducing effective and broadly cross-reactive humoral and cellular immune responses remains a challenging task because of the extensive diversity of HIV-1, the difference of virus subtypes (clades) in different geographical regions, and the polymorphism of human leukocyte antigens (HLA). We performed an in silico design of 3 DNA vaccines, designated pJW4303-MEG1, pJW4303-MEG2 and pJW4303-MEG3, encoding multi-epitopes that are highly conserved within the HIV-1 subtypes most prevalent in China and can be recognized through HLA alleles dominant in China. The pJW4303-MEG1-encoded protein consisted of one Th epitope in Env, and one, 2, and 6 epitopes in Pol, Env, and Gag proteins, respectively, with a GGGS linker sequence between epitopes. The pJW4303-MEG2-encoded protein contained similar epitopes in a different order, but with the same linker as pJW4303-MEG1. The pJW4303-MEG3-encoded protein contained the same epitopes in the same order as that of pJW4303-MEG2, but with a different linker sequence (AAY). To evaluate immunogenicity, mice were immunized intramuscularly with these DNA vaccines. Both pJW4303-MEG1 and pJW4303-MEG2 vaccines induced equally potent humoral and cellular immune responses in the vaccinated mice, while pJW4303-MEG3 did not induce immune responses. These results indicate that both epitope and linker sequences are important in designing effective epitope-based vaccines against HIV-1 and other viruses.
authors.affiliation: a State Key Laboratory of Pathogen and Biosecurity ; Beijing Institute of Microbiology and Epidemiology ; Beijing , China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.forename: Weilai
authors.initials: W
authors.lastname: Sun
authors.forename: Jingjing
authors.initials: J
authors.lastname: Guo
authors.forename: Guangyu
authors.initials: G
authors.lastname: Zhao
authors.forename: Shihui
authors.initials: S
authors.lastname: Sun
authors.forename: Hong
authors.initials: H
authors.lastname: Yu
authors.forename: Yan
authors.initials: Y
authors.lastname: Guo
authors.forename: Jungfeng
authors.initials: J
authors.lastname: Li
authors.forename: Xia
authors.initials: X
authors.lastname: Jin
authors.forename: Lanying
authors.initials: L
authors.lastname: Du
authors.forename: Shibo
authors.initials: S
authors.lastname: Jiang
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Kou
authors.forename: Yusen
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology*; D000818:Animals; D044466:Asian People; D002681:China; D003198:Computer Simulation; D015195:Drug Design; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D005260:Female; D015483:HIV Antibodies / Q000097:blood; D015488:HIV Antigens / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007273:Injections, Intramuscular; D008214:Lymphocytes / Q000276:immunology; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D000939:Epitopes; D015483:HIV Antibodies; D015488:HIV Antigens; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic
keywords: AIDS, acquired immunodeficiency syndrome; BSA, bovine serum albumin; CRF, circulating recombinant form; CTL, cytotoxic T lymphocyte; DNA vaccine; HIV, human immunodeficiency virus; HIV-1; HLA; HLA, human leukocyte antigen; MEG, multi-epitope genes; MHC, major histocompatibility complex; SFU, spot forming units; linker; multi-epitope
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