Abstract
Viral infection typically originates from a limited number of virions known as transmitted/founder (T/F) viruses. Studies of cross-species transmission, and intra-species transmission of antigenically variable viruses, indicates T/F variants may express distinct, transmissibility enhancing phenotypes. However, with evidence that transmissibility is associated with not only intrinsic virological features, such as virion composition, but also extrinsic factors, such as viral population structure, the challenge of resolving T/F signatures that can be targeted by rational vaccine or antiviral design is substantial. Nonetheless, failure to develop vaccines for antigenically variable viruses, such as HIV/HCV, and the ongoing risk of cross-species transmission with pandemic potential, recommends development of T/F targeting vaccines. In this commentary, the T/F phenomena is introduced, explored in both the classical (HIV) and non-canonical (coronaviruses) instances, and discussed in relation to rational and preemptive vaccine design.