Attenuation of Bovine Parainfluenza Virus Type 3 in Nonhuman Primates and Its Ability to Confer Immunity to Human Parainfluenza Virus Type 3 Challenge

1988 ◽  
Vol 157 (4) ◽  
pp. 655-662 ◽  
Author(s):  
K. L. van Wyke Coelingh ◽  
C. C. Winter ◽  
E. L. Tierney ◽  
W. T. London ◽  
B. R. Murphy
2013 ◽  
Vol 19 (9) ◽  
Author(s):  
Michihito Sasaki ◽  
Akihiro Ishii ◽  
Yasuko Orba ◽  
Yuka Thomas ◽  
Bernard M. Hang’ombe ◽  
...  

2000 ◽  
Vol 74 (24) ◽  
pp. 11626-11635 ◽  
Author(s):  
Aurelia A. Haller ◽  
Tessa Miller ◽  
Misrach Mitiku ◽  
Kathleen Coelingh

ABSTRACT Bovine parainfluenza virus type 3 (bPIV3) is being evaluated as an intranasal vaccine for protection against human PIV3 (hPIV3). In young infants, the bPIV3 vaccine appears to be infectious, attenuated, immunogenic, and genetically stable, which are desirable characteristics for an RNA virus vector. To test the potential of the bPIV3 vaccine strain as a vector, an infectious DNA clone of bPIV3 was assembled and recombinant bPIV3 (r-bPIV3) was rescued. r-bPIV3 displayed a temperature-sensitive phenotype for growth in tissue culture at 39°C and was attenuated in the lungs of Syrian golden hamsters. In order to test whether r-bPIV3 could serve as a vector, the fusion and hemagglutinin-neuraminidase genes of bPIV3 were replaced with those of hPIV3. The resulting bovine/human PIV3 was temperature sensitive for growth in Vero cells at 37°C. The replication of bovine/human PIV3 was also restricted in the lungs of hamsters, albeit not as severely as was observed for r-bPIV3. Despite the attenuation phenotypes observed for r-bPIV3 and bovine/human PIV3, both of these viruses protected hamsters completely upon challenge with hPIV3. In summary, bPIV3 was shown to function as a virus vector that may be especially suitable for vaccination of infants and children against PIV3 and other viruses.


2003 ◽  
Vol 84 (12) ◽  
pp. 3253-3261 ◽  
Author(s):  
Sridhar Pennathur ◽  
Aurelia A. Haller ◽  
Mia MacPhail ◽  
Tom Rizzi ◽  
Sepideh Kaderi ◽  
...  

Restricted replication in the respiratory tract of rhesus monkeys is an intrinsic property of bovine parainfluenza virus type 3 (bPIV-3) strains. This host range phenotype of bPIV-3 has been utilized as a marker to evaluate the attenuation of bPIV-3 vaccines for human use. Two safety, immunogenicity and efficacy studies in primates evaluated and compared three human parainfluenza virus type 3 (hPIV-3) vaccine candidates: biologically derived bPIV-3, a plasmid-derived bPIV-3 (r-bPIV-3) and a chimeric bovine/human PIV-3 (b/hPIV-3). These studies also examined the feasibility of substituting Vero cells, cultured in the presence or absence of foetal bovine serum, for foetal rhesus lung-2 (FRhL-2) cells as the tissue culture substrate for the production of bPIV-3 vaccine. The results demonstrated that (i) Vero cell-produced bPIV-3 was as attenuated, immunogenic and efficacious as bPIV-3 vaccine grown in FRhL-2 cells, (ii) plasmid-derived bPIV-3 was as attenuated, immunogenic and efficacious as the biologically derived bPIV-3 and (iii) the b/hPIV-3 chimera displayed an intermediate attenuation phenotype and protected animals completely from hPIV-3 challenge. These results support the use of bPIV-3 vaccines propagated in Vero cells in human clinical trials and the use of b/hPIV-3 as a virus vaccine vector to express foreign viral antigens.


2000 ◽  
Vol 74 (24) ◽  
pp. 11792-11799 ◽  
Author(s):  
Maria-Arantxa Horga ◽  
G. Luca Gusella ◽  
Olga Greengard ◽  
Natalia Poltoratskaia ◽  
Matteo Porotto ◽  
...  

ABSTRACT Viral interference is characterized by the resistance of infected cells to infection by a challenge virus. Mechanisms of viral interference have not been characterized for human parainfluenza virus type 3 (HPF3), and the possible role of the neuraminidase (receptor-destroying) enzyme of the hemagglutinin-neuraminidase (HN) glycoprotein has not been assessed. To determine whether continual HN expression results in depletion of the viral receptors and thus prevents entry and cell fusion, we tested whether cells expressing wild-type HPF3 HN are resistant to viral infection. Stable expression of wild-type HN-green fluorescent protein (GFP) on cell membranes in different amounts allowed us to establish a correlation between the level of HN expression, the level of neuraminidase activity, and the level of protection from HPF3 infection. Cells with the highest levels of HN expression and neuraminidase activity on the cell surface were most resistant to infection by HPF3. To determine whether this resistance is attributable to the viral neuraminidase, we used a cloned variant HPF3 HN that has two amino acid alterations in HN leading to the loss of detectable neuraminidase activity. Cells expressing the neuraminidase-deficient variant HN-GFP were not protected from infection, despite expressing HN on their surface at levels even higher than the wild-type cell clones. Our results demonstrate that the HPF3 HN-mediated interference effect can be attributed to the presence of an active neuraminidase enzyme activity and provide the first definitive evidence that the mechanism for attachment interference by a paramyxovirus is attributable to the viral neuraminidase.


2008 ◽  
Vol 77 (2) ◽  
pp. 83-94 ◽  
Author(s):  
Hongxia Mao ◽  
Chandar S. Thakur ◽  
Santanu Chattopadhyay ◽  
Robert H. Silverman ◽  
Andrei Gudkov ◽  
...  

2021 ◽  
pp. 105053
Author(s):  
Fu-lu Chu ◽  
Hong-ling Wen ◽  
Gui-hua Hou ◽  
Bin Lin ◽  
Wen-qiang Zhang ◽  
...  

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