Transient IL-10 receptor blockade can enhance CD8(+) T cell responses to a simian adenovirus-vectored HIV-1 conserved region immunogen.
Viral vector vaccines designed to elicit CD8(+) T cells in non-human primates exert potent control of immunodeficiency virus infections; however, similar approaches have been unsuccessful in humans. Adenoviral vectors elicit potent T cell responses but also induce production of immunosuppressive interleukin-10 (IL-10), which can limit the expansion of T cell responses. We investigated whether inhibiting IL-10 signaling prior to immunization with a candidate adenovirus vectored-HIV-1 vaccine, ChAdV63.HIVconsv, could modulate innate and adaptive immune responses in BALB/c mice. Transient IL-10 receptor blockade led to a modest but significant increase in the total magnitude CD8(+) T cell response to HIVconsv, but did not affect T cell responses to immunodominant epitopes. Anti-IL-10R-treated animals also exhibited greater expression of CD86 on CD11c(+) dendritic cells. Our data support further investigation and optimization of IL-10 blocking strategies to improve the immunogenicity of vaccines based on replication-defective adenoviruses.
a The Jenner Institute Laboratories ; University of Oxford ; Oxford , UK.
Genevieve
G
Clutton
Anne
A
Bridgeman
Arturo
A
Reyes-Sandoval
Tomas
T
Hanke
Lucy
L
Dorrell
D016915:AIDS Vaccines; D000261:Adenoviruses, Simian / Q000235:genetics*; D000818:Animals; D051940:B7-2 Antigen / Q000378:metabolism; D039521:CD11c Antigen / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D005822:Genetic Vectors / Q000235:genetics*; D015483:HIV Antibodies; D015658:HIV Infections; D015497:HIV-1 / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D053701:Receptors, Interleukin-10 / Q000037:antagonists & inhibitors*
D016915:AIDS Vaccines; D051940:B7-2 Antigen; D039521:CD11c Antigen; D015483:HIV Antibodies; D053701:Receptors, Interleukin-10
HIV-1; T cells; interleukin-10; mouse