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Transcriptomic profiling of young and old rhesus macaques vaccinated with DNA/ALVAC+gp120

ABSTRACT: The development of an effective vaccine to protect against HIV acquisition will be greatly bolstered by in-depth understanding of the innate and adaptive responses to the virus. We report here that the efficacy of DNA/ALVAC/gp120/alum vaccines, based on V2-specific antibodies mediating apoptosis of infected cells (V2-ADCC), is complemented by efferocytosis, a cyclic AMP (cAMP)-dependent antiphlogistic engulfment of apoptotic cells by CD14+ monocytes. Central to vaccine efficacy is the engagement of the CCR2+/CCL2 axis and tolerogenic dendritic cells producing IL-10 (DC-10). Durable epigenetic reprogramming in CD14+ cells of the cyclic AMP/CREB pathway and increased levels of miRNA-139-5p, a negative regulator of expression of the cAMP-specific phosphodiesterase PDE4D, in extracellular vesicles correlated with vaccine efficacy. These data posit that efferocytosis, through the prompt and effective removal of apoptotic infected cells, contributes to vaccine efficacy by decreasing inflammation and maintaining tissue homeostasis.

ORGANISM(S): Macaca mulatta

PROVIDER: GSE188901 | GEO | 2022/12/28

REPOSITORIES: GEO

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