Human parainfluenza virus type 3 (PIV3) expressing the hemagglutinin protein of measles virus provides a potential method for immunization against measles virus and PIV3 in early infancy
Ap. Durbin et al., Human parainfluenza virus type 3 (PIV3) expressing the hemagglutinin protein of measles virus provides a potential method for immunization against measles virus and PIV3 in early infancy, J VIROLOGY, 74(15), 2000, pp. 6821-6831
Recombinant human parainfluenza virus type 3 (PIV3) was used as a vector to
express the major protective antigen of measles virus, the hemagglutinin (
HA) glycoprotein, in order to create a bivalent PIV3-measles virus that can
be administered intranasally. The measles virus HA open reading frame (ORF
) was inserted as an additional transcriptional unit into the N-P, P-M, or
HA-neuraminidase (HN)-L gene junction of wild-type PIV3 or into the N-P or
P-hl gene junction of an attenuated derivative of PIV3, termed rcp45L. The
recombinant PIV3 (rPIV3) viruses bearing the IIA inserts replicated more sl
owly in vitro than their parental viruses but reached comparable peak titer
s of greater than or equal to 10(7.5) 50% tissue culture infective doses pe
r mi. Each of the wild-type or cold-passaged 45L (cp35L) PIV3(IIA) chimeric
viruses replicated 5- to 10-fold less well than its respective parent viru
s in the upper respiratory tract of hamsters, Thus, insertion of the simila
r to 2-kb ORF itself conferred attenuation, and this attenuation was additi
ve to that conferred by the cp35L mutations. The attenuated cp45L PIV3(HA)
recombinants induced a high level of resistance to replication of PIV3 chal
lenge virus in hamsters and induced very high levels of measles virus neutr
alizing antibodies (>1:8,000) that are well in excess of those known to be
protective in humans. rPIV3s expressing the HA gene in the N-P or P-hl junc
tion induced about 400-fold more measles virus-neutralizing antibody than d
id the rPIV3 with the HA gene in the HN-L junction, indicating that the N-P
or P-M junction appears to be the preferred insertion site. Previous studi
es indicated that the PIV3 cp45 virus, a more attenuated version of rcp45L,
replicates efficiently in the respiratory tract of monkeys and is immunoge
nic and protective even when administered in the presence of very high tite
rs of passively transferred PIV3 antibodies (A. P, Durbin, C. J, Cho, W, R
Elkins, L, S, Wyatt, B, Moss, and B, R Murphy, J, Infect. Dis, 179:1345-135
1, 1999). This suggests that this intranasally administered PIV3(HA) chimer
ic virus can be used to immunize infants with maternally acquired measles v
irus antibodies in whom the current parenterally administered live measles
virus vaccine is ineffective.