The effect of adenovirus-specific antibodies on adenoviral vector–induced, transgene product–specific T cell responses

JC Small, LH Haut, A Bian… - Journal of leukocyte …, 2014 - academic.oup.com
JC Small, LH Haut, A Bian, HCJ Ertl
Journal of leukocyte biology, 2014academic.oup.com
In this study, we tested the effect of neutralizing Abs to different serotypes of E1-deleted Ad
vectors on the immunogenicity of the homologous Ad vector or a vector derived from a
heterologous serotype. Our results showed that, as expected, even low titers of passively
transferred neutralizing Abs significantly reduced the homologous vectors' ability to elicit
transgene-specific CD8+ T cell responses. In addition, Abs changed the fate of transgene
product–specific CD8+ T cells by promoting their transition into the central memory cell pool …
Abstract
In this study, we tested the effect of neutralizing Abs to different serotypes of E1-deleted Ad vectors on the immunogenicity of the homologous Ad vector or a vector derived from a heterologous serotype. Our results showed that, as expected, even low titers of passively transferred neutralizing Abs significantly reduced the homologous vectors' ability to elicit transgene-specific CD8+ T cell responses. In addition, Abs changed the fate of transgene product–specific CD8+ T cells by promoting their transition into the central memory cell pool, which resulted in markedly enhanced expansion of transgene product–specific CD8+ T cells after a boost with a heterologous Ad vector. Non-neutralizing Abs specific to a distinct Ad serotype had no effect on the magnitude of transgene product-specific CD8+ T cells induced by a heterologous Ad vector, nor did such Abs promote induction of more resting memory CD8+ T cells. These results show that Abs to an Ad vaccine carrier affect not only the magnitude but also the profile of a vector-induced CD8+ T cell response.
Oxford University Press