Laboratory and Pre-Clinical Studies of Parainfluenza Type 3 Virus

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 is in the final stages of licensure 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. This candidate vaccine virus replicates to high titer in a licensed cell substrate and clinical lots of vaccine virus that are attenuated and stable phenotypically in monkeys will be evaluated this year in humans. 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 that are the major protective antigens of PIV3. Immunization of rhesus monkeys with the MVA-PIV3 recombinant viruses induced complete protection against infection by a wild type (wt) PIV3 challenge.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Allergy and Infectious Diseases (NIAID)
• Type: Intramural Research (Z01)
• Project #: 1Z01AI000327-15
• Application #: 2566745
• Study Section: Special Emphasis Panel (LID)
• Support Year: 15
• Fiscal Year: 1996

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