Laboratory and Pre-Clinical Studies of Parainfluenza Viruses

Murphy, B R.

Abstract

Two live-attenuated parainfluenza virus type 3 (PIV3) candidate vaccines have completed Phase I trials in human infants and children. A bovine PIV3 that is antigenically related to the human PIV3 has been licensed to a biotechnology company that will pursue its further development. The second candidate, the cold-passaged (cp45) mutant of human PIV3, is being studied further under a CRADA between NIAID/LID and a pharmaceutical manufacturer. Infectious PIV3 has been recovered from cells transfected with PIV3 full-length cDNA in the presence of the needed accessory factors, and this new capability opens up the possibility for the rapid development of vaccines for PIV1, PIV2, and PIV3 using recombinant cDNA technology. A highly attenuated vaccinia virus vector (MVA), that should be completely safe for immunocompromised humans, was used to express the viral surface HN and F glycoproteins which are the major protective antigens of PIV3. Immunization of rhesus monkeys with the MVA-PIV3 recombinant viruses induced protection against replication of challenge virus in the lower, but not the upper, respiratory tract despite the mucosal administration of the recombinant vaccine candidate.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Allergy and Infectious Diseases (NIAID)
• Type: Intramural Research (Z01)
• Project #: 1Z01AI000327-16
• Application #: 6160586
• Study Section: Special Emphasis Panel (LID)
• Support Year: 16
• Fiscal Year: 1997

Institution

• Name: National Institute of Allergy and Infectious Diseases
• Country: United States

Publications

Boonyaratanakornkit, Jim B; Bartlett, Emmalene J; Amaro-Carambot, Emerito et al. (2009) The C proteins of human parainfluenza virus type 1 (HPIV1) control the transcription of a broad array of cellular genes that would otherwise respond to HPIV1 infection. J Virol 83:1892-910

Bartlett, Emmalene J; Hennessey, Margaret; Skiadopoulos, Mario H et al. (2008) Role of interferon in the replication of human parainfluenza virus type 1 wild type and mutant viruses in human ciliated airway epithelium. J Virol 82:8059-70

Bartlett, Emmalene J; Cruz, Ann-Marie; Esker, Janice et al. (2008) Human parainfluenza virus type 1 C proteins are nonessential proteins that inhibit the host interferon and apoptotic responses and are required for efficient replication in nonhuman primates. J Virol 82:8965-77

Nolan, Sheila M; Skiadopoulos, Mario H; Bradley, Konrad et al. (2007) Recombinant human parainfluenza virus type 2 vaccine candidates containing a 3'genomic promoter mutation and L polymerase mutations are attenuated and protective in non-human primates. Vaccine 25:6409-22

Bartlett, Emmalene J; Castano, Adam; Surman, Sonja R et al. (2007) Attenuation and efficacy of human parainfluenza virus type 1 (HPIV1) vaccine candidates containing stabilized mutations in the P/C and L genes. Virol J 4:67

Surman, Sonja R; Collins, Peter L; Murphy, Brian R et al. (2007) An improved method for the recovery of recombinant paramyxovirus vaccine candidates suitable for use in human clinical trials. J Virol Methods 141:30-3

Bartlett, Emmalene J; Amaro-Carambot, Emerito; Surman, Sonja R et al. (2006) Introducing point and deletion mutations into the P/C gene of human parainfluenza virus type 1 (HPIV1) by reverse genetics generates attenuated and efficacious vaccine candidates. Vaccine 24:2674-84

Van Cleve, William; Amaro-Carambot, Emerito; Surman, Sonja R et al. (2006) Attenuating mutations in the P/C gene of human parainfluenza virus type 1 (HPIV1) vaccine candidates abrogate the inhibition of both induction and signaling of type I interferon (IFN) by wild-type HPIV1. Virology 352:61-73

Nolan, Sheila M; Surman, Sonja R; Amaro-Carambot, Emerito et al. (2005) Live-attenuated intranasal parainfluenza virus type 2 vaccine candidates developed by reverse genetics containing L polymerase protein mutations imported from heterologous paramyxoviruses. Vaccine 23:4765-74

Bartlett, Emmalene J; Amaro-Carambot, Emerito; Surman, Sonja R et al. (2005) Human parainfluenza virus type I (HPIV1) vaccine candidates designed by reverse genetics are attenuated and efficacious in African green monkeys. Vaccine 23:4631-46