In silico design of a DNA-based HIV-1 multi-epitope vaccine for Chinese populations.

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.