Specific antibodies modulate the interactions of adenovirus type 5 with dendritic cells.
Adenovirus type 5 (Ad5) is able to induce an efficient CD8+ T lymphocyte (CTL) response against a transgene product, a property thought to be linked to its ability to transduce dendritic cells (DCs). Little, however, is known about the capacity of Ad5 to interact with DCs in the presence of specific antibodies, although most people test positive for antibodies directed against Ad5. In the present study, we found that in the presence of Ad5 antibodies, a large fraction of Ad5 binds very efficiently to DCs, and that this binding is FcgammaRII/FcgammaRIII dependent. Nevertheless, in the presence of high levels of antibodies against the whole virion, Ad5 entry was inhibited. Increased binding led to increased entry in DCs in the presence of fiber-specific antibodies or in the presence of low amounts of a whole antiserum raised against whole virions, showing that the relative concentration of antibodies directed against fiber and penton base plays a major role in entry efficacy. Nevertheless, mice previously immunized with virions or purified fiber developed a lower transgene-specific CD8+ T cell response than naive mice, although their serum appeared to increase virus entry into DCs in vitro.
Mercier
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UMR INRA-AFSSA-ENVA 1161, Virologie, Ecole Nationale Vétérinaire d'Alfort, 94704 Maisons-Afort Cedex, France.
Rouard
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Delfau-Larue
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Eloit
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D000260:Adenoviruses, Human / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D000918:Antibody Specificity; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology*; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D007114:Immunization; D051379:Mice; D008810:Mice, Inbred C57BL; D009500:Neutralization Tests; D017452:Receptors, IgG / Q000378:metabolism; D014161:Transduction, Genetic
D000914:Antibodies, Viral; D036022:Capsid Proteins; D017452:Receptors, IgG; C018315:hexon capsid protein, Adenovirus; C043322:penton protein, adenovirus