Multi-pathogen and combination vaccines for biodefense pathogens

Multi-pathogen and combination vaccines are vaccines that deliver antigens from two or more pathogens in a single shot to protect against multiple diseases. This can include several individual vaccines formulated together to be delivered as a single shot as well as multivalent vaccines, where a single vaccine expresses or contains multiple antigens. Multi-pathogen vaccines present an obvious solution for rapidly protecting a population against multiple biological threat agents simultaneously. They also have additional cost and logistical advantages over delivering separate vaccines. However, data from childhood combination vaccines have shown that they do not always perform as the sum of their parts, so ensuring that newly developed multi-pathogen vaccines protect as well as their individual vaccine counterparts can be challenging. Here, we focus on three core mechanisms of vaccine interference; epitope competition, resource competition and immune polarization, and discuss how multi-pathogen vaccines across different platforms (viral vectors, bacterial vectors, protein/subunit and nucleic acid) are impacted by each mechanism. We review multi-pathogen vaccines in development for pathogens and toxins that pose a biological threat, and propose an evaluation metric for assessing potential adverse combinations of vaccines. This review is intended to provide information relevant for platform-selection for developing biodefense vaccines for stockpiling and rapid deployment.