HIV fragment gag vaccine induces broader T cell response in mice

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.