Three new studies report progress in the drive to rationally design AIDS vaccines that can teach the immune system how to mount an effective antibody response against the virus. Some HIV-infected people make “broadly neutralizing” antibodies (bNAbs) that work against a wide array of viral variants, but researchers have struggled to figure out how to reverse engineer them. Two reports online this week in Science and one in Cell show in animal experiments that two different approaches can help steer antibody-producing B cells onto pathways that ultimately will produce bNAbs. One strategy uses a nanoparticle based on a small part of HIV’s surface protein, gp120, as an “immunogen” to kick-start the bNAb process. A second effort uses a natural mimic of the entire gp120 as it appears on viral surfaces, clumped together in groups of three known as trimers. Ultimately, researchers believe they will need to combine the nanoparticle, natural trimer, and other unknown immunogens to make a vaccine that can stop most every HIV variant circulating through humans around the world.