scholarly journals 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

2001 ◽  
Vol 75 (10) ◽  
pp. 4594-4603 ◽  
Author(s):  
Alexander C. Schmidt ◽  
Josephine M. McAuliffe ◽  
Brian R. Murphy ◽  
Peter L. Collins
Keyword(s):  
Respiratory Syncytial Virus ◽  
Respiratory Tract ◽  
Host Range ◽  
Virus Type ◽  
Serum Antibody ◽  
Parainfluenza Virus ◽  
Range Restriction ◽  
Syncytial Virus ◽  
Human Parainfluenza Virus ◽  
Type 3

ABSTRACT Recombinant bovine/human parainfluenza virus type 3 (rB/HPIV3), a recombinant bovine PIV3 (rBPIV3) in which the F and HN genes were replaced with their HPIV3 counterparts, was used to express the major protective antigens of respiratory syncytial virus (RSV) in order to create a bivalent mucosal vaccine against RSV and HPIV3. The attenuation of rB/HPIV3 is provided by the host range restriction of the BPIV3 backbone in primates. RSV G and F open reading frames (ORFs) were placed under the control of PIV3 transcription signals and inserted individually into the rB/HPIV3 genome in the promoter-proximal position preceding the nucleocapsid protein gene. The recombinant PIV3 expressing the RSV G ORF (rB/HPIV3-G1) was not restricted in its replication in vitro, whereas the virus expressing the RSV F ORF (rB/HPIV3-F1) was eightfold restricted compared to its rB/HPIV3 parent. Both viruses replicated efficiently in the respiratory tract of hamsters, and each induced RSV serum antibody titers similar to those induced by RSV infection and anti-HPIV3 titers similar to those induced by HPIV3 infection. Immunization of hamsters with rB/HPIV3-G1, rB/HPIV3-F1, or a combination of both viruses resulted in a high level of resistance to challenge with RSV or HPIV3 28 days later. These results describe a vaccine strategy that obviates the technical challenges associated with a live attenuated RSV vaccine, providing, against the two leading viral agents of pediatric respiratory tract disease, a bivalent vaccine whose attenuation phenotype is based on the extensive host range sequence differences of BPIV3.

scholarly journals Mucosal Immunization of Rhesus Monkeys against Respiratory Syncytial Virus Subgroups A and B and Human Parainfluenza Virus Type 3 by Using a Live cDNA-Derived Vaccine Based on a Host Range-Attenuated Bovine Parainfluenza Virus Type 3 Vector Backbone

2002 ◽  
Vol 76 (3) ◽  
pp. 1089-1099 ◽  
Author(s):  
Alexander C. Schmidt ◽  
Daniel R. Wenzke ◽  
Josephine M. McAuliffe ◽  
Marisa St. Claire ◽  
William R. Elkins ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Respiratory Tract ◽  
Host Range ◽  
Virus Type ◽  
Rhesus Monkeys ◽  
Parainfluenza Virus ◽  
Protective Antigens ◽  
Syncytial Virus ◽  
Human Parainfluenza Virus ◽  
Type 3

ABSTRACT Reverse genetics was used to develop a two-component, trivalent live attenuated vaccine against human parainfluenza virus type 3 (HPIV3) and respiratory syncytial virus (RSV) subgroups A and B. The backbone for each of the two components of this vaccine was the attenuated recombinant bovine/human PIV3 (rB/HPIV3), a recombinant BPIV3 in which the bovine HN and F protective antigens are replaced by their HPIV3 counterparts (48). This chimera retains the well-characterized host range attenuation phenotype of BPIV3, which appears to be appropriate for immunization of young infants. The open reading frames (ORFs) for the G and F major protective antigens of RSV subgroup A and B were each placed under the control of PIV3 transcription signals and inserted individually or in homologous pairs as supernumerary genes in the promoter proximal position of rB/HPIV3. The level of replication of rB/HPIV3-RSV chimeric viruses in the respiratory tract of rhesus monkeys was similar to that of their parent virus rB/HPIV3, and each of the chimeras induced a robust immune response to both RSV and HPIV3. RSV-neutralizing antibody titers induced by rB/HPIV3-RSV chimeric viruses were equivalent to those induced by infection with wild-type RSV, and HPIV3-specific antibody responses were similar to, or slightly less than, after infection with the rB/HPIV3 vector itself. This study describes a novel vaccine strategy against RSV in which vaccine viruses with a common attenuated backbone, specifically rB/HPIV3 derivatives expressing the G and/or F major protective antigens of RSV subgroup A and of RSV subgroup B, are used to immunize by the intranasal route against RSV and HPIV3, which are the first and second most important viral agents of pediatric respiratory tract disease worldwide.

scholarly journals Attenuation of the Recombinant Human Parainfluenza Virus Type 3 cp45 Candidate Vaccine Virus Is Augmented by Importation of the Respiratory Syncytial Virus cpts530 L Polymerase Mutation

Virology ◽  
1999 ◽  
Vol 260 (1) ◽  
pp. 125-135 ◽  
Author(s):  
Mario H. Skiadopoulos ◽  
Sonja R. Surman ◽  
Marisa St. Claire ◽  
William R. Elkins ◽  
Peter L. Collins ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Virus Type ◽  
Vaccine Virus ◽  
Candidate Vaccine ◽  
Parainfluenza Virus ◽  
Syncytial Virus ◽  
Human Parainfluenza Virus ◽  
Type 3

scholarly journals 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

2000 ◽  
Vol 74 (7) ◽  
pp. 3188-3195 ◽  
Author(s):  
Jane E. Bailly ◽  
Josephine M. McAuliffe ◽  
Anna P. Durbin ◽  
William R. Elkins ◽  
Peter L. Collins ◽  
...  
Keyword(s):  
Host Range ◽  
Virus Type ◽  
Rhesus Monkeys ◽  
Parainfluenza Virus ◽  
Antigenic Determinants ◽  
Range Restriction ◽  
N Protein ◽  
Human Parainfluenza Virus ◽  
Type 3 ◽  
Host Range Restriction

ABSTRACT The shipping fever (SF) and Kansas (Ka) strains of bovine parainfluenza virus type 3 (BPIV3) are restricted in their replication in rhesus monkeys 100- to 1,000-fold compared to human parainfluenza virus type 3 (HPIV3), and the Ka strain also was shown to be attenuated in humans. To initiate an investigation of the genetic basis of the attenuation of BPIV3 in primates, we produced viable chimeric HPIV3 recombinants containing the nucleoprotein (N) open reading frame (ORF) from either BPIV3 Ka or SF in place of the HPIV3 N ORF. These chimeric recombinants were designated cKa-N and cSF-N, respectively. Remarkably, cKa-N and cSF-N grew to titers comparable to those of their HPIV3 and BPIV3 parents in LLC-MK2 monkey kidney and Madin-Darby bovine kidney cells. Thus, the heterologous nature of the N protein did not impede replication in vitro. However, cKa-N and cSF-N were each restricted in replication in rhesus monkeys to a similar extent as Ka and SF, respectively. This identified the BPIV3 N protein as a determinant of the host range restriction of BPIV3 in primates. These chimeras thus combine the antigenic determinants of HPIV3 with the host range restriction and attenuation phenotype of BPIV3. Despite their restricted replication in rhesus monkeys, the chimeric viruses induced a level of resistance to HPIV3 challenge in these animals which was indistinguishable from that conferred by immunization with HPIV3. The infectivity, attenuation, and immunogenicity of these BPIV3/HPIV3 chimeras suggest that the modified Jennerian approach described in the present report represents a novel method to design vaccines to protect against HPIV3-induced disease in humans.

scholarly journals A Prototype Recombinant Vaccine Against Respiratory Syncytial Virus and Parainfluenza Virus Type 3

1994 ◽  
Vol 12 (8) ◽  
pp. 813-818 ◽  
Author(s):  
Run-Pan Du ◽  
Gail E. D. Jackson ◽  
Philip R. Wyde ◽  
Wei-Yao Yan ◽  
Qijun Wang ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Virus Type ◽  
Recombinant Vaccine ◽  
Parainfluenza Virus ◽  
Syncytial Virus ◽  
Type 3

scholarly journals Determinants of the Host Range Restriction of Replication of Bovine Parainfluenza Virus Type 3 in Rhesus Monkeys Are Polygenic

2003 ◽  
Vol 77 (2) ◽  
pp. 1141-1148 ◽  
Author(s):  
Mario H. Skiadopoulos ◽  
Alexander C. Schmidt ◽  
Jeffrey M. Riggs ◽  
Sonja R. Surman ◽  
William R. Elkins ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Host Range ◽  
Rhesus Monkeys ◽  
Single Unit ◽  
Parainfluenza Virus ◽  
Wild Type ◽  
Range Restriction ◽  
Type 3 ◽  
Bovine Parainfluenza Virus ◽  
Host Range Restriction

ABSTRACT The Kansas strain of bovine parainfluenza virus type 3 (BPIV3) is 100- to 1,000-fold restricted in replication in the respiratory tracts of nonhuman primates compared to human PIV3 (HPIV3), an important pathogen of infants and young children. BPIV3 is also restricted in replication in human infants and children, yet it is immunogenic and is currently being evaluated in clinical trials as a vaccine candidate to protect against illness caused by HPIV3. We have examined the genetic basis for the host range attenuation phenotype of BPIV3 by exchanging each open reading frame (ORF) of a recombinant wild-type HPIV3 with the analogous ORF from BPIV3, with the caveats that the multiple ORFs of the P gene were exchanged as a single unit and that the HN and F genes were exchanged as a single unit. Recombinant chimeric bovine-human PIV3s were recovered from cDNA, and the levels of viral replication in vitro and in the respiratory tract of rhesus monkeys were determined. Recombinant chimeric HPIV3s bearing the BPIV3 N or P ORF were highly attenuated in the upper and lower respiratory tracts of monkeys, whereas those bearing the BPIV3 M or L ORF or the F and HN genes were only moderately attenuated. This indicates that the genetic determinants of the host range restriction of replication of BPIV3 for primates are polygenic, with the major determinants being the N and P ORFs. Monkeys immunized with these bovine-human chimeric viruses, including the more highly attenuated ones, developed higher levels of HPIV3 hemagglutination-inhibiting serum antibodies than did monkeys immunized with BPIV3 and were protected from challenge with wild-type HPIV3. Furthermore, host range determinants could be combined with attenuating point mutations to achieve an increased level of attenuation. Thus, chimeric recombinant bovine-human PIV3 viruses that manifest different levels of attenuation in rhesus monkeys are available for evaluation as vaccine candidates to protect infants from the severe lower respiratory tract disease caused by HPIV3.

Sign in / Sign up

Export Citation Format

Share Document