Immunoglobulin G1 (IgG1), IgG2a, and IgG2b switch variants were derived from an IgG3 monoclonal antibody directed against the VP3 envelope glycoprotein of lactate dehydrogenase-elevating virus (LDV). Among the four antibodies, IgG2a delayed the onset and progression of LDV-induced polioencephalomyelitis more than did the other subclasses. This suggests that the IgG2a predominance observed in many IgG antibody responses elicited by live viruses could, at least under some circumstances, correspond to the selection of the best protection for the infected host.