Dissociation of porcine reproductive and respiratory syndrome virus neutralization from antibodies specific to major envelope protein surface epitopes

► PRRSV neutralization is attributed to major envelope protein linear epitopes. ► Epitope-containing ectodomains protect in the absence of neutralizing antibodies. ► Ectodomain polypeptides do not block PRRSV infection of permissive macrophages. ► Envelope protein ectodomains are not associated with antibody neutralization. ► Linear ectodomain sequences on GP5 are not targets of PRRSV neutralizing antibodies.