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.
Journal article
Hum Vaccin Immunother
2015
11
1030 - 1035
HIV-1, T cells, interleukin-10, mouse, AIDS Vaccines, Adenoviruses, Simian, Animals, B7-2 Antigen, CD11c Antigen, CD8-Positive T-Lymphocytes, Enzyme-Linked Immunospot Assay, Female, Genetic Vectors, HIV Antibodies, HIV Infections, HIV-1, Mice, Mice, Inbred BALB C, Receptors, Interleukin-10