 The Human Vaccines Project was launched in 2015 with the mission to decode the human immune response to accelerate development of vaccines and immunotherapies for major diseases by deciphering the complete repertoire of B and T cell receptors across the human population, understanding the key principles of how a vaccine elicits a protective and durable response using a system immunology approach, and conducting experimental clinical trials to understand the influence of influenza pre-exposures on subsequent influenza immunization and the mechanisms of protection. This article was authored by Stacey L. Wooden and Wayne Seacoff.