Oral or parenteral administration of replication-deficient adenoviruses expressing the measles virus haemagglutinin and fusion proteins: protective immune responses in rodents.
The genes encoding the measles virus (MV) haemagglutinin (H) and fusion (F) proteins were placed under the control of the human cytomegalovirus immediate early promoter in a replication-deficient adenovirus vector. Immunofluorescence and radioimmune precipitation demonstrated the synthesis of each protein and biological activity was confirmed by the detection of haemadsorption and fusion activities in infected cells. Oral as well as parenteral administration of the H-expressing recombinant adenovirus elicited a significant protective response in mice challenged with MV. While the F-expressing adenovirus failed to protect mice, cotton rats immunized with either the H- or F-expressing recombinant showed reduced MV replication in the lungs. Antibodies elicited in mice following immunization with either recombinant had no in vitro neutralizing activity, suggesting a protective mechanism involving a cell-mediated immune response. This study demonstrates the feasibility of using oral administration of adenovirus recombinants to induce protective responses to heterologous proteins.
Fooks
A R
AR
Centre for Applied Microbiology and Research, Porton Down, Salisbury, UK. anthony.fooks@camr.org.uk
Jeevarajah
D
D
Lee
J
J
Warnes
A
A
Niewiesk
S
S
ter Meulen
V
V
Stephenson
J R
JR
Clegg
J C
JC
D000256:Adenoviridae / Q000502:physiology; D000284:Administration, Oral; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D002460:Cell Line; D002461:Cell Line, Transformed; D003673:Defective Viruses / Q000502:physiology; D005260:Female; D005822:Genetic Vectors; D006389:Hemagglutinins, Viral / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007274:Injections, Intraperitoneal; D008457:Measles / Q000517:prevention & control*; D008458:Measles Vaccine / Q000276:immunology*; D008459:Measles virus / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D051381:Rats; D016205:Sigmodontinae; D014760:Viral Fusion Proteins / Q000235:genetics / Q000276:immunology*; D014779:Virus Replication
D000914:Antibodies, Viral; D006389:Hemagglutinins, Viral; D008458:Measles Vaccine; D014760:Viral Fusion Proteins; C032397:hemagglutinin protein G, measles virus