Canine parvovirus (CPV) is an important viral pathogen of dogs and related animals, which causes severe enteritis in animals of many ages or myocarditis in puppies, with both conditions frequently leading to fatal outcomes. CPV emerged in 1978 in dogs to cause a pandemic disease, and it has continued to circulate and evolve since then, including the acquisition of sequence changes that result in new antigenic variants. Modified live virus vaccines are routinely administered to prevent CPV infection, but a number of reports of vaccine failure have resulted in debates as to whether they provide complete protection against recent viral variants. While we now know a lot about the sequences and variation of the virus, we know few details about the antibody response against CPV in infected or vaccinated dogs, or in the maternal antibodies that both protect puppies against infection and also block vaccination. My goal is to characterize the specificity of the antibody response against CPV in dogs, to determine the cross immunity between viruses with natural capsid variation, and to determine whether that variation allows escape from antibody neutralization. These studies will provide new insights into the protection provided by vaccine- or infection-derived antibodies against different CPV variants. I hypothesize that the canine antibody response against CPV protects by targeting several distinct epitopes, but that some epitopes overlap the receptor binding site, which constrains viral evolution and selection of antigenic variants.