A chimeric human-bovine parainfluenza virus type 3 expressing measles virus hemagglutinin is attenuated for replication but is still immunogenic in rhesus monkeys.
The chimeric recombinant virus rHPIV3-N(B), a version of human parainfluenza virus type 3 (HPIV3) that is attenuated due to the presence of the bovine PIV3 nucleocapsid (N) protein open reading frame (ORF) in place of the HPIV3 ORF, was modified to encode the measles virus hemagglutinin (HA) inserted as an additional, supernumerary gene between the HPIV3 P and M genes. This recombinant, designated rHPIV3-N(B)HA, replicated like its attenuated rHPIV3-N(B) parent virus in vitro and in the upper and lower respiratory tracts of rhesus monkeys, indicating that the insertion of the measles virus HA did not further attenuate rHPIV3-N(B) in vitro or in vivo. Monkeys immunized with rHPIV3-N(B)HA developed a vigorous immune response to both measles virus and HPIV3, with serum antibody titers to both measles virus (neutralizing antibody) and HPIV3 (hemagglutination inhibiting antibody) of over 1:500. An attenuated HPIV3 expressing a major protective antigen of measles virus provides a method for immunization against measles by the intranasal route, a route that has been shown with HPIV3 and respiratory syncytial virus vaccines to be relatively refractory to the neutralizing and immunosuppressive effects of maternally derived virus-specific serum antibodies. It should now be possible to induce a protective immune response against measles virus in 6-month-old infants, an age group that in developing areas of the world is not responsive to the current measles virus vaccine.
Skiadopoulos
M H
MH
Respiratory Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. mskiadopoulos@niaid.nih.gov
Surman
S R
SR
Riggs
J M
JM
Collins
P L
PL
Murphy
B R
BR
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002417:Cattle; D002678:Chimera; D006389:Hemagglutinins, Viral / Q000276:immunology*; D006801:Humans; D007114:Immunization; D008253:Macaca mulatta; D008458:Measles Vaccine / Q000276:immunology*; D010224:Parainfluenza Virus 3, Human / Q000235:genetics* / Q000254:growth & development / Q000276:immunology; D012137:Respiratory System / Q000821:virology; D018108:Respirovirus / Q000235:genetics*; D014613:Vaccines, Attenuated / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology*; D014779:Virus Replication
D000914:Antibodies, Viral; D006389:Hemagglutinins, Viral; D008458:Measles Vaccine; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic