Effect of preexisting immunity on an adenovirus vaccine vector: in vitro neutralization assays fail to predict inhibition by antiviral antibody in vivo.
A major obstacle to the use of adenovirus vectors derived from common human serotypes, such as human adenovirus 5 (AdHu5), is the high prevalence of virus-neutralizing antibodies in the human population. We previously constructed a variant of chimpanzee adenovirus 68 (AdC68) that maintained the fundamental properties of the carrier but was serologically distinct from AdC68 and resisted neutralization by AdC68 antibodies. In the present study, we tested whether this modified vector, termed AdCDQ, could induce transgene product-specific CD8(+) T cells in mice with preexisting neutralizing antibody to wild-type AdC68. Contrary to our expectation, the data show conclusively that antibodies that fail to neutralize the AdCDQ mutant vector in vitro nevertheless impair the vector's capacity to transduce cells and to stimulate a transgene product-specific CD8(+) T-cell response in vivo. The results thus suggest that in vitro neutralization assays may not reliably predict the effects of virus-specific antibodies on adenovirus vectors in vivo.
Pichla-Gollon
Susan L
SL
Division of Infectious Diseases, the Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA. susan.l.gollon@gsk.com
Lin
Shih-Wen
SW
Hensley
Scott E
SE
Lasaro
Marcio O
MO
Herkenhoff-Haut
Larissa
L
Drinker
Mark
M
Tatsis
Nia
N
Gao
Guang-Ping
GP
Wilson
James M
JM
Ertl
Hildegund C J
HC
Bergelson
Jeffrey M
JM
D000256:Adenoviridae / Q000235:genetics* / Q000276:immunology*; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology* / Q000494:pharmacology*; D000918:Antibody Specificity; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D017930:Genes, Reporter / Q000235:genetics; D005822:Genetic Vectors / Q000235:genetics* / Q000276:immunology*; D007118:Immunoassay; D051379:Mice; D008807:Mice, Inbred BALB C; D011961:Receptors, Fc / Q000276:immunology; D019076:Transgenes / Q000235:genetics; D014765:Viral Vaccines / Q000276:immunology*
D000914:Antibodies, Viral; D011961:Receptors, Fc; D014765:Viral Vaccines