Parvovirus Capsid-Antibody Complex Structures Reveal Conservation of Antigenic Epitopes Across the Family

The parvoviruses are small nonenveloped single stranded DNA viruses that constitute members that range from apathogenic to pathogenic in humans and animals. The infection with a parvovirus results in the generation of antibodies against the viral capsid by the host immune system to eliminate the virus and to prevent re-infection. For members currently either being developed as delivery vectors for gene therapy applications or as oncolytic biologics for tumor therapy, efforts are aimed at combating the detrimental effects of pre-existing or post-treatment antibodies that can eliminate therapeutic benefits. Therefore, understanding antigenic epitopes of parvoviruses can provide crucial information for the development of vaccination applications and engineering novel capsids able to escape antibody recognition. This review aims to capture the information for the binding regions of ∼30 capsid-antibody complex structures of different parvovirus capsids determined to date by cryo-electron microscopy and three-dimensional image reconstruction. The comparison of all complex structures revealed the conservation of antigenic regions among parvoviruses from different genera despite low sequence identity and indicates that the available data can be used across the family for vaccine development and capsid engineering.