Generation of a recombinant Oka varicella vaccine expressing mumps virus hemagglutinin-neuraminidase protein as a polyvalent live vaccine.
We constructed a recombinant varicella-zoster virus (VZV) Oka vaccine strain (vOka) that contained the mumps virus (MuV) hemagglutinin-neuraminidase (HN) gene, inserted into the site of the ORF 13 gene by using the bacterial artificial chromosome (BAC) system in Escherichia coli. Insertion of the HN gene into the VZV genome was confirmed by PCR and Southern blot. The infectious virus reconstituted from the vOka-HN genome (rvOka-HN) had a growth curve similar to the original recombinant vOka without the HN gene. The mumps virus HN protein expressed in rvOka-HN infected cells was expressed diffusely in the cytoplasm, and modification of the protein was similar to that seen in MuV-infected cells. Electron microscopic examination of infected cells revealed that HN was expressed on the plasma membrane of the cells but not in the viral envelope, suggesting that the tropism of rvOka-HN would be unchanged from that of the original vOka strain. Immunization of guinea pigs with rvOka-HN-induced VZV- and HN-specific antibodies. Interestingly, the induced antibodies had a strong neutralizing activity against virus-cell infections of both MuV and VZV. Therefore, the novel varicella vaccine expressing MuV HN protein is suitable as a polyvalent live attenuated vaccine against VZV and MuV infections.
Laboratory of Virology and Vaccinology, Division of Biomedical Research, National Institute of Biomedical Innovation, 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan.
Pranee
P
Somboonthum
Hironori
H
Yoshii
Shigefumi
S
Okamoto
Masato
M
Koike
Yasuyuki
Y
Gomi
Yasuo
Y
Uchiyama
Michiaki
M
Takahashi
Koichi
K
Yamanishi
Yasuko
Y
Mori
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry; D019433:Chickenpox Vaccine / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D022202:Chromosomes, Artificial, Bacterial; D004926:Escherichia coli / Q000235:genetics; D006168:Guinea Pigs; D006389:Hemagglutinins, Viral / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008297:Male; D046529:Microscopy, Electron, Transmission; D016253:Microscopy, Immunoelectron; D009109:Mumps virus / Q000235:genetics / Q000276:immunology*; D009439:Neuraminidase / Q000235:genetics / Q000276:immunology; D009500:Neutralization Tests; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology; D014771:Virion / Q000737:chemistry
D000914:Antibodies, Viral; D019433:Chickenpox Vaccine; D006389:Hemagglutinins, Viral; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D009439:Neuraminidase