Single oral immunization with replication deficient recombinant adenovirus elicits long-lived transgene-specific cellular and humoral immune responses.
Oral-gastric delivery of vaccines is a preferred route of immunization and is particularly relevant to the development of vaccine-vector systems. We have investigated the ability of a replication deficient (E1-deleted) adenovirus construct (RAd68), which efficiently expresses the measles virus nucleocapsid (N) protein under the control of the strong HCMV IE promoter, to elicit antibody and cytotoxic T cell (CTL) responses in mice following intragastric administration. Measles virus N protein-specific CTL memory and serum antibody responses were analyzed in a total of 140 mice at time points 2-51 weeks after immunization either with a single dose of 10(8) pfu RAd68 or with a fivefold higher dose. Of the 20 animals analyzed in the first 4-week period following low-dose immunization, 6 mounted low-level splenic CTL responses while 13 animals had CTL in the mesenteric lymph nodes. Splenic CTL responses were largely undetectable at later times. Only 23% of low-dose-immunized mice made serum antibody responses and these were generally of low magnitude and frequently of short duration. In contrast, the majority of animals immunized orally with 5 x 10(8) pfu RAd68 mounted splenic CTL responses (70%) and/or antibody responses (89%). Notably, these responses were stronger and of greater duration than those seen following immunization at the lower dose. Gut mucosal immunization with replication deficient adenoviruses is a promising approach, not only for the development of complementary measles vaccine strategies which may be required for measles virus eradication, but also generally for vaccination against other infections.
Sharpe
Sally
S
Centre for Applied Microbiology and Research, Salisbury SP4 0JG, United Kingdom. sally.sharpe@camr.org.uk
Fooks
Anthony
A
Lee
John
J
Hayes
Kevin
K
Clegg
Christopher
C
Cranage
Martin
M
D000256:Adenoviridae / Q000235:genetics / Q000276:immunology*; D017498:Adenovirus E1 Proteins / Q000172:deficiency / Q000235:genetics; D000284:Administration, Oral; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis* / Q000097:blood; D004306:Dose-Response Relationship, Immunologic; D005822:Genetic Vectors; D008198:Lymph Nodes / Q000276:immunology; D008457:Measles / Q000517:prevention & control; D051379:Mice; D008809:Mice, Inbred C3H; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000096:biosynthesis; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013997:Time Factors; D014611:Vaccination / Q000379:methods; D014614:Vaccines, Synthetic; D014764:Viral Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000276:immunology
D017498:Adenovirus E1 Proteins; D000914:Antibodies, Viral; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D014764:Viral Proteins; D014765:Viral Vaccines; C058314:nucleoprotein, Measles virus