Langerhans cells are more efficiently transduced than dermal dendritic cells by adenovirus vectors expressing either group C or group B fibre protein: implications for mucosal vaccines.
Vaccines against viruses need to target dendritic cells (DC) and stimulate mucosal immunity. Most vaccine studies have focussed on monocyte-derived or dermal DC (dDC) but recent evidence suggests that Langerhans cells (LC) may stimulate mucosal immunity more effectively. New chimeric adenovirus vectors expressing fibre protein from group B adenoviruses (rAd5/11), which utilise CD46 rather than the Coxsackie adenovirus receptor (CAR), have been developed as vaccines to improve transduction and overcome problems of pre-existing vector immunity. Transduction of LC and dDC by rAd5/11 and standard rAd5 expressing green fluorescent protein (GFP) showed that both DC types were more efficiently transduced by rAd5/11 than by rAd5. Although expression of CD46 and the integrins alphavbeta3 and alphavbeta5, which recognise the adenovirus penton base and mediate virus internalisation, was similar in LC and dDC, LC expressed higher levels of GFP. Transduction by electroporation of plasmid also resulted in higher GFP expression in LC, suggesting differences between the two DC populations at a post-entry stage. Transduction with either vector did not induce maturation of LC or dDC and did not affect their ability to stimulate T cells. These findings suggest that vaccine strategies that target LC with adenovirus vectors may be worthy of exploration.
Rozis
George
G
Department of Immunology, Imperial College, Chelsea & Westminster Hospital, London, UK.
de Silva
Shamika
S
Benlahrech
Adel
A
Papagatsias
Timos
T
Harris
Julian
J
Gotch
Frances
F
Dickson
George
G
Patterson
Steven
S
D000256:Adenoviridae / Q000235:genetics / Q000276:immunology; D018952:Antigens, CD34 / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000502:physiology* / Q000821:virology; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology*; D016130:Immunophenotyping; D007801:Langerhans Cells / Q000276:immunology / Q000502:physiology* / Q000821:virology; D008213:Lymphocyte Activation; D010957:Plasmids / Q000235:genetics; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D014161:Transduction, Genetic / Q000379:methods*; D015854:Up-Regulation; D014765:Viral Vaccines / Q000276:immunology*
D018952:Antigens, CD34; D019013:CD40 Antigens; D014765:Viral Vaccines; D049452:Green Fluorescent Proteins