Vaccination is estimated to prevent more than 4 million deaths annually, representing one of the most effective public health tools to prevent death and disease. Yet vaccines remain enigmatic against some of the most deadly pathogens and diseases globally, in part due to our incomplete understanding of the immune responses associated with disease control and clearance. However, over the past 3 decades , we have experienced an explosion in immunological tools, that have effectively revolutionized our understanding of immunological mechanisms involved in the control of the host-pathogen interaction. Linked to new vaccine platforms, adjuvants, and antigen design, the ability to strategically shape immunity is emerging. This meeting will focus on defining key vaccine associated immunological obstacles and discuss current and future immunological solutions that may lead to the development of next generation vaccines able to straetically harness immunity to fight disease. Significance: The COVID-19 pandemic catalyzed an extraordinary revolution in vaccinology, accelerating the development of novel antigen design/discovery strategies, clinical trial conduct, as well as novel vaccine platforms/tools. However, vaccines are still lacking for some of our most lethal pathogens, partly due to our incomplete understanding of immune correlates of protection. Moreover, additional vaccine gaps exist that continue to limit the universal efficacy of some of our most critical vaccines. Thus, this keystone meeting aims to take a deep look at the current immunological gaps in vaccinology. This meeting will bring together international immunological leaders in vaccinology and infectious disease to define the challenges and discuss creative new solutions to fully leverage the immune response to maximize the potential of vaccines. Immunologists and vaccinologists from across virology, bacteriology, and oncology will come together to tackle 4 fundamental questions: 1. How are T/B cells trained in inductive sites and how can these responses be engineered for breadth, full potency, and durability 2. How can vaccines drive long-lived tissue resident immunity able to provide maximal protection against infection and disease 3. How can immune correlates help advance vaccine development 4. Will therapeutic vaccines fully leverage immunity to chronic pathogens and tumors. Collectively, interaction of leaders from disparate areas of vaccinology and immunology will create a new dialogue, catalyze new collaborations, inspire new approaches to overcome immunological obstacles and accelerate discovery of vaccines across a wide range of diseases. Attendees will learn about the common challenges across vaccine development efforts and find converging opportunities to overcome and improve immunogenicity and vaccine efficacy. Innovation: While vaccine development often focuses on the pathogen, this meeting will uniquely approach vaccine design and development with an immunological lens. The meeting will focus on key challenges and approaches to leverage immunology in vaccine development and raise opportunities to re-engineer and train the immune system to fight a broad range of infections and diseases. The meeting will bring together academic and industry vaccinologists and immunologists, strategically catalyzing discussions around common challenges across vaccine development fields. The structure and selection of speakers will enable attendees to not only rapidly appreciate the common immunological obstacles faced across vaccine development efforts, but also appreciate the rapidly evolving new technologies and immune mechanistic understanding that will help solve these challenges. The venue and arrangement of sessions will further support the growth of new collaborations and inspire the next generation of vaccinologists to take a new vantage point in leveraging the host:disease axis. Thus, ultimately, the meeting will bridge fields of vaccinology through common immunological struggles and create new networks of vaccinologists and immunologists apt to take vaccinology to the next frontier.