Efficient immunization of rhesus macaques with an HCV candidate vaccine by heterologous priming-boosting with novel adenoviral vectors based on different serotypes.
Efficient vaccination against viral agents requires a strong T-cell-mediated immune response to clear viral-infected cells. Optimal vaccination can be achieved by administration of recombinant viral vectors encoding phatogen antigens. Adenoviral vectors have attracted considerable attention as potential viral vectors for genetic vaccination owing to their favorable safety profile and potent transduction efficiency following intramuscular injection. However, the neutralizing antibody response against adenoviral capsid proteins following adenoviral vectors injection limits the success of vaccination protocols based on multiple administrations of the same adenoviral serotype. In this work, we describe efficient immunization of rhesus macaques, the preferred model for preclinical assessment, with an HCV candidate vaccine by heterologous priming-boosting with adenoviral vectors based on different serotypes. The induced responses are broad and show significant cross-strain reactivity. Boosting can be delayed for over 2 years after priming, indicating that there is long-term maintenance of resting memory cells.
Fattori
E
E
Department of Molecular and Cellular Biololgy, Istituto di Ricerche di Biologia Molecolare P Angeletti, Pomezia, Rome, Italy. elena_fattori@merck.com
Zampaglione
I
I
Arcuri
M
M
Meola
A
A
Ercole
B B
BB
Cirillo
A
A
Folgori
A
A
Bett
A
A
Cappelletti
M
M
Sporeno
E
E
Cortese
R
R
Nicosia
A
A
Colloca
S
S
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D005818:Genetic Engineering; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000235:genetics; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics* / Q000276:immunology; D006526:Hepatitis C / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D007115:Immunization Schedule; D007117:Immunization, Secondary; D007371:Interferon-gamma / Q000276:immunology; D008253:Macaca mulatta; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology; D014761:Viral Hepatitis Vaccines / Q000008:administration & dosage* / Q000235:genetics
D000914:Antibodies, Viral; D014761:Viral Hepatitis Vaccines; D007371:Interferon-gamma