title: Induction of strong protection by vaccination with partially attenuated serotype 1 Marek's disease viruses.
abstract: Studies were conducted to better understand the relationship among Marcek's disease (MD) vaccine strains between induction of protective immunity and the degree of attenuation (or virulence). To obtain viruses at different stages of attenuation, very virulent plus MD strains 584A and 648A and selected clones of these strains were serially passaged in chicken and duck cells. These viruses were considered fully attenuated after passage for 70-100 times in chicken embryo cell cultures until they no longer induced gross lesions in susceptible, maternal antibody-negative (ab-) chickens. Lower passages of the same strains were considered partially attenuated, provided their virulence was less than that of the parent strain. Four of five partially attenuated preparations derived from MD virus strains 584A and 648A or the previously attenuated Md11 strain induced 28%-62% higher levels of protection in maternal antibody-positive (ab+) chickens against virulent MD challenge than the fully attenuated counterpart viruses. The partially attenuated 584A/d2/3 strain replicated in chickens but was totally nonprotective. Data from two subsequent trials in ab+ chickens confirmed that protection induced by the partly attenuated (passage 80) preparations was 79% and 118% higher, respectively, than that induced by the fully attenuated (passage 100) preparations of strain 648A. However, in one trial with ab- chickens, no difference in protection between partially and fully attenuated virus was observed. Strong protection (up to 85%) against highly virulent challenge also was provided by preparations of 648A at passages 40-60, which were moderately oncogenic when used alone. Partially attenuated strains tended to replicate to higher titers in both ab+ and ab- chickens compared with fully attenuated vaccines. Also, ab+ and ab- chickens vaccinated with partially attenuated strains developed three- to nine fold more extensive microscopic lesions in peripheral nerves at 14 and 22 days after virulent challenge than chickens vaccinated with fully attenuated strains. When measured in ab+ chickens, loss of lesion induction by 648A was achieved 30 passages earlier (at passage 70) than when measured in ab- chickens. Thus, maternal antibodies appeared to abrogate the pathogenicity of some partially attenuated strains. These studies establish for MD the principle that at least some partially attenuated MD viruses may replicate better and induce stronger immunity against virulent challenge than fully attenuated preparations of the same strain, at least when tested in ab+ chickens. Moreover, depending on passage level, partially attenuated vaccine strains may be relatively innocuous for ab+ chickens, causing few or no lesions.
authors.affiliation: USDA, Agricultural Research Service, Avian Disease and Oncology Laboratory, 3606 E. Mt. Hope Road, East Lansing, MI 48823, USA.
authors.forename: R L
authors.initials: RL
authors.lastname: Witter
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000917:Antibody Formation; D002645:Chickens; D008381:Herpesvirus 2, Gallid / Q000276:immunology* / Q000472:pathogenicity; D008380:Marek Disease / Q000276:immunology* / Q000517:prevention & control; D014613:Vaccines, Attenuated; D014765:Viral Vaccines; D014774:Virulence
chemical_list: D000914:Antibodies, Viral; D014613:Vaccines, Attenuated; D014765:Viral Vaccines