Evaluation in non-human primates of the safety, immunogenicity and efficacy of recombinant vaccinia viruses expressing the F or G glycoprotein of respiratory syncytial virus.
It has been shown previously that immunization with recombinant vaccinia viruses expressing the F or G envelope glycoprotein of human respiratory syncytial virus (RSV) strain A2 induced a protective immune response in the lower respiratory tract of cotton rats against live RSV challenge. As a continuation of these studies, the safety, immunogenicity and efficacy of these recombinant vaccinia viruses was evaluated in non-human primates. Rhesus and patas monkeys were each inoculated intradermally at separate sites with the vaccinia-A2-F or vaccinia-A2-G recombinant or the parental vaccinia virus WR strain and the dermal lesion sizes were compared. Vaccinia-A2-F and vaccinia-A2-G recombinants produced lesions that were 5- to 15-fold smaller in area than vaccinia-WR. These studies indicated that insertion of either RSV gene into the thymidine kinase (TK) gene of vaccinia-WR significantly attenuated the virus for rhesus and patas monkeys. The immunogenicity of vaccinia-A2-F and vaccinia-A2-G was evaluated in squirrel, rhesus, African green, owl and patas monkeys. In four of the five species tested, the vaccinia-RSV recombinants stimulated levels of RSV serum-neutralizing antibodies considered to be protective for the lower respiratory tract of human infants and cotton rats. Interestingly, the level of RSV serum-neutralizing antibodies correlated with the size of the lesion. A boost in RSV serum-neutralizing antibody titres was not observed following a second inoculation. Owl monkeys inoculated with a single intradermal dose of vaccinia-A2-F and vaccinia-A2-G were completely resistant to infection of the lower respiratory tract with live RSV.(ABSTRACT TRUNCATED AT 250 WORDS)
Olmsted
R A
RA
Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.
Buller
R M
RM
Collins
P L
PL
London
W T
WT
Beeler
J A
JA
Prince
G A
GA
Chanock
R M
RM
Murphy
B R
BR
D000818:Animals; D001029:Aotus trivirgatus; D003411:Arvicolinae; D015707:HN Protein; D007109:Immunity; D007114:Immunization; D011994:Recombinant Proteins / Q000502:physiology; D012136:Respiratory Syncytial Viruses; D012453:Saimiri; D014616:Vaccinia virus / Q000235:genetics*; D014759:Viral Envelope Proteins / Q000502:physiology*; D014760:Viral Fusion Proteins / Q000502:physiology*; D014764:Viral Proteins
D015707:HN Protein; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins; D014764:Viral Proteins; C116204:attachment protein G