20962088
not annotated - annotated - LINNAEUS only
Multiple innate immune pathways contribute to the immunogenicity of recombinant adenovirus vaccine vectors.
The innate immune pathways that contribute to the potent immunogenicity of recombinant adenovirus (rAd) vaccine vectors remain largely undefined. Previous studies assessing innate immunity triggered by vaccine vectors have largely focused on in vitro studies involving antigen-presenting cells and on early in vivo inflammatory responses. Here, we systematically explore the Toll-like receptor (TLR) signaling requirements for the generation of cellular immune responses by intramuscular immunization with common and alternative serotype rAd vectors in mice. Antigen-specific CD8(+) T-lymphocyte responses elicited by these rAd vectors were significantly diminished in MyD88(-/-) mice but not in TRIF(-/-) or TLR3(-/-) mice, suggesting the importance of MyD88-dependent TLR signaling. However, the absence of each individual TLR resulted in minimal to no effect on vaccine-elicited cellular immune responses. Moreover, responses were not diminished in IL-1R(-/-) or IL-18R(-/-) mice. These data suggest that rAd vectors engage multiple MyD88-dependent signaling pathways, none of which are individually critical; rather, they are integrated to contribute to the potent immunogenicity of rAd vectors. Stimulation of multiple innate immune mechanisms may prove a generalizable property of potent vaccines, and this strategy could be harnessed in the development of next-generation vaccine vectors and adjuvants.
Ann file
T1 Species 663 667 mice
T2 Species 790 794 mice
T3 Species 829 833 mice
T4 Species 1088 1092 mice
N1 Reference T1 Taxonomy:10090 Mus musculus
N2 Reference T2 Taxonomy:10090 Mus musculus
N3 Reference T3 Taxonomy:10090 Mus musculus
N4 Reference T4 Taxonomy:10090 Mus musculus
T5 Out-of-scope 80 90 adenovirus
T6 Out-of-scope 197 207 adenovirus
N5 Reference T5 Taxonomy:10508 Adenoviridae
N6 Reference T6 Taxonomy:10508 Adenoviridae