The quest for an effective AIDS vaccine is still ongoing by various vaccine research centres, but some major challenges are remaining. Among those is how to overcome the extensive diversity of HIV-1. Global mosaic vaccine design, one of the strategies, has recently been shown enhancing the breadth of T-cell immune responses in NHP studies. However, this global mosaic theoretically may not cover well for South-East Asian HIV-1 subtype, of which CRF01_AE is the most prevalent subtype. Therefore, our team has designed various sets of SEA HIV-1 AE/B’ mosaic DNA vaccines, including gag, pol, nef, and env. The design is based on 156/72, 150/210, 101/30 and 113/59 Asian AE/Asian B HIV-1 sequences, respectively. By modelling analysis, SEA HIV-1 AE/B’ gag mosaic may provide more than 80% 9-mers matched with subtype AE, as compared with 70% of global gag mosaic cocktail. Mice immunised with three doses of AE/B mosaic via in vivo elec-troportion had shown different median IFNγ ELISpot responses to HIV-1 AE versus B truncated pool peptides, i.e., gag mosaic induced approximately 900 versus 700 SFCs/10 6 splenocytes; env mosaic showed approximately similar responses of 900 SFCs/10 6 splenocytes to both pool peptides; whereas the responses to AE peptides were lower in pol and nef mosaic (700 versus 1500, 200 versus 800 SFCs/10 6 splenocytes), respectively. In the study of three doses of AE/B env mosaic DNA primed and r-vaccinia boosted, boosting with r-AE vaccinia but not r-B vaccinia significantly enhanced the ELiSpot responses. The next steps are to evaluate these mosaic vaccines in humanised mice and non-human primates (NHPs) to compare whether these SEA HIV-1 AE/B mosaic vaccine candidates will indeed be more beneficial to the currently designed global mosaic in enhancing T cell breadth and coverage for Asian HIV-1 AE and B viruses.