Explore new approaches to vaccine development and HIV/TB research in this lecture from the HU CFAR Annual Symposium. Delve into successful licensed vaccine classes, liposome delivery systems, and innovative strategies for stable lipid nanoparticles. Learn about interbilayer-crosslinked multilamellar vesicles (CMV) and their efficiency in delivering antigens to lymph node cells. Discover the potential of ICMV nanocapsules in eliciting long-lived, high-avidity humoral responses and their application in needle-free mucosal vaccination. Examine the importance of vaccination location and clinically validated strategies for lymph node targeting. Investigate the use of albumin hitch-hiking to keep CpG at local immune induction sites and avoid systemic inflammation. Finally, explore the application of amphiphile vaccines to HIV, focusing on designing long peptide antigens to constrain viral fitness and maximize vaccine efficacy and safety.