期刊
HUMAN VACCINES & IMMUNOTHERAPEUTICS
卷 11, 期 3, 页码 795-805出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/21645515.2015.1012017
关键词
DNA vaccine; HLA; HIV-1; linker; multi-epitope; AIDS; acquired immunodeficiency syndrome; BSA; bovine serum albumin; CRF; circulating recombinant form; CTL; cytotoxic T lymphocyte; HIV; human immunodeficiency virus; HLA; human leukocyte antigen; MEG; multi-epitope genes; MHC; major histocompatibility complex; SFU; spot forming units
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.
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