Evaluation of bovine, cold-adapted human, and wild-type human parainfluenza type 3 viruses in adult volunteers and in chimpanzees.
In an attempt to evaluate the level of attenuation of live parainfluenza type 3 virus (PIV3) vaccine candidates, we compared the responses of partially immune adult volunteers inoculated intranasally with 10(6) to 10(7) 50% tissue culture infective dose (TCID50) of bovine PIV3 (n = 18) or cold-adapted (ca) PIV3 (n = 37) with those of 28 adults administered 10(6) to 10(7) TCID50 of wild-type PIV3. The candidate vaccine viruses and the wild-type virus were avirulent and poorly infectious for these adults even though all of them had a low level of nasal antibodies to PIV3. To determine whether the ca PIV3 was attenuated, we then administered 10(4) TCID50 of ca PIV3 (cold-passage 12) or wild-type PIV3 intranasally and intratracheally to two fully susceptible chimpanzees, respectively, and challenged the four primates with wild-type virus 1 month later. Compared with wild-type virus, which caused upper respiratory tract illness, the ca PIV3 was highly attenuated and manifested a 500-fold reduction in virus replication in both the upper and lower respiratory tracts of the two immunized animals. Despite restriction of virus replication, infection with ca PIV3 conferred a high level of protective immunity against challenge with wild-type virus. The ca PIV3 which had been passaged 12 times at 20 degrees C did not retain its ts phenotype. These findings indicate that ca PIV3 may be a promising vaccine candidate for human beings if a passage level can be identified that is genetically stable, satisfactorily attenuated, and immunogenic.
Clements
M L
ML
Department of International Health, Johns Hopkins University School of Hygiene Public Health, Baltimore, Maryland.
Belshe
R B
RB
King
J
J
Newman
F
F
Westblom
T U
TU
Tierney
E L
EL
London
W T
WT
Murphy
B R
BR
D000222:Adaptation, Physiological; D000293:Adolescent; D000328:Adult; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D002417:Cattle; D003080:Cold Temperature; D005069:Evaluation Studies as Topic; D006801:Humans; D009154:Mutation; D002679:Pan troglodytes; D010224:Parainfluenza Virus 3, Human / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D018184:Paramyxoviridae Infections / Q000517:prevention & control; D014613:Vaccines, Attenuated / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*; D014774:Virulence; D014779:Virus Replication
D000914:Antibodies, Viral; D014613:Vaccines, Attenuated; D014765:Viral Vaccines