Adenovirus hexon protein is a potent adjuvant for activation of a cellular immune response.
The capacity of recombinant adenoviruses (rAd) to induce immunization against their transgene products has been well documented. In the present study, we evaluated the vaccinal adjuvant role of rAd independently of its vector function. BALB/c mice received one subcutaneous injection of a mixture of six lipopeptides (LP6) used as a model immunogen, along with AdE1 degrees (10(9) particles), a first-generation rAd empty vector. Although coinjected with a suboptimal dose of lipopeptides, AdE1 degrees significantly improved the effectiveness of the vaccination, even in the absence of booster immunization. In contrast to mice that received LP6 alone or LP6 plus a mock adjuvant, mice injected with AdE1 degrees plus LP6 developed both a polyspecific T-helper type 1 response and an effector CD8 T-cell response specific to at least two class I-restricted epitopes. The helper response was still observed when immunization was performed using LP6 plus a mixture of soluble capsid components released from detergent-disrupted virions. When mice were immunized with LP6 and each individual capsid component, i.e., hexon, penton base, or fiber, the results obtained suggested that hexon protein was responsible for the adjuvant effect exerted by disrupted Ad particles on the helper response to the immunogen. Our results thus have some important implications not only in vaccinology but also for gene therapy using rAd vectors.
Molinier-Frenkel
Valérie
V
Laboratoire d'Immunologie des Pathologies Infectieuses et Tumorales, INSERM U445, Institut Cochin de Génétique Moléculaire, Hôpital Cochin, 75014 Paris, France. frenkel@cochin.inserm.fr
Lengagne
Renée
R
Gaden
Florence
F
Hong
Saw-See
SS
Choppin
Jeannine
J
Gahery-Ségard
Hanne
H
Boulanger
Pierre
P
Guillet
Jean-Gérard
JG
D000256:Adenoviridae / Q000235:genetics / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000008:administration & dosage* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002213:Capsid / Q000008:administration & dosage* / Q000276:immunology; D036022:Capsid Proteins; D005822:Genetic Vectors; D007111:Immunity, Cellular; D007114:Immunization; D007376:Interleukin-2 / Q000032:analysis; D008074:Lipoproteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D011995:Recombination, Genetic; D018417:Th1 Cells / Q000276:immunology
D000276:Adjuvants, Immunologic; D000956:Antigens, Viral; D036022:Capsid Proteins; D007376:Interleukin-2; D008074:Lipoproteins; D010446:Peptide Fragments; C018315:hexon capsid protein, Adenovirus