This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Clements, M L Articles by Murphy, B R Search for Related Content PubMed PubMed Citation Articles by Clements, M L Articles by Murphy, B R

Evaluation of bovine, cold-adapted human, and wild-type human parainfluenza type 3 viruses in adult volunteers and in chimpanzees.

Department of International Health, Johns Hopkins University School of Hygiene Public Health, Baltimore, Maryland.

ABSTRACT

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.

This article has been cited by other articles:

• Bukreyev, A., Yang, L., Zaki, S. R., Shieh, W.-J., Rollin, P. E., Murphy, B. R., Collins, P. L., Sanchez, A. (2006). A Single Intranasal Inoculation with a Paramyxovirus-Vectored Vaccine Protects Guinea Pigs against a Lethal-Dose Ebola Virus Challenge. J. Virol. 80: 2267-2279 [Abstract] [Full Text]  
• Bukreyev, A., Huang, Z., Yang, L., Elankumaran, S., St. Claire, M., Murphy, B. R., Samal, S. K., Collins, P. L. (2005). Recombinant Newcastle Disease Virus Expressing a Foreign Viral Antigen Is Attenuated and Highly Immunogenic in Primates. J. Virol. 79: 13275-13284 [Abstract] [Full Text]  
• Henrickson, K. J. (2003). Parainfluenza Viruses. Clin. Microbiol. Rev. 16: 242-264 [Abstract] [Full Text]  
• Schmidt, A. C., McAuliffe, J. M., Murphy, B. R., Collins, P. L. (2001). Recombinant Bovine/Human Parainfluenza Virus Type 3 (B/HPIV3) Expressing the Respiratory Syncytial Virus (RSV) G and F Proteins Can Be Used To Achieve Simultaneous Mucosal Immunization against RSV and HPIV3. J. Virol. 75: 4594-4603 [Abstract] [Full Text]  
• Schmidt, A. C., McAuliffe, J. M., Huang, A., Surman, S. R., Bailly, J. E., Elkins, W. R., Collins, P. L., Murphy, B. R., Skiadopoulos, M. H. (2000). Bovine Parainfluenza Virus Type 3 (BPIV3) Fusion and Hemagglutinin-Neuraminidase Glycoproteins Make an Important Contribution to the Restricted Replication of BPIV3 in Primates. J. Virol. 74: 8922-8929 [Abstract] [Full Text]  
• Tao, T., Skiadopoulos, M. H., Davoodi, F., Riggs, J. M., Collins, P. L., Murphy, B. R. (2000). Replacement of the Ectodomains of the Hemagglutinin-Neuraminidase and Fusion Glycoproteins of Recombinant Parainfluenza Virus Type 3 (PIV3) with Their Counterparts from PIV2 Yields Attenuated PIV2 Vaccine Candidates. J. Virol. 74: 6448-6458 [Abstract] [Full Text]  
• Bailly, J. E., McAuliffe, J. M., Durbin, A. P., Elkins, W. R., Collins, P. L., Murphy, B. R. (2000). A Recombinant Human Parainfluenza Virus Type 3 (PIV3) in Which the Nucleocapsid N Protein Has Been Replaced by That of Bovine PIV3 Is Attenuated in Primates. J. Virol. 74: 3188-3195 [Abstract] [Full Text]