Influence of vaccine-induced mucosal NKp44+ and mucosal NKp44−NKG2A− cells on SIVinfection outcomes in rhesus macaques

Abstract

Abstract NK cells play an essential role in control of viral infection. We investigated NK cell dynamics and function post-vaccination with replicating adenovirus (Ad)-SIV recombinants and SIV envelope and subsequent intravaginal exposure to SIV. Macaques that became infected were studied. As no differences in NK cell frequencies or cytokine production were seen between vaccinated and Ad-empty/alum controls, suggesting responses observed were due to the Ad-vector and alum immunizations, the groups were combined. Mucosal NKp44+ NK cells increased post-vaccination and returned to pre-levels post-infection. Post-vaccination NKp44+ cell frequencies tended to correlate (p = 0.070, r = 0.683) while NKp44+IL-17+ cell frequencies positively correlated (p = 0.042, r = 0.742) with number of challenges for SIV acquisition. Additionally, negative correlations with peak viral load (VL) (p = 0.0072, r = −0.881) and chronic median VL (p = 0.0107, r = −0.857) suggested that these IL-17+ cells might inhibit SIV acquisition by promoting epithelial integrity and mucosal homeostasis. In contrast, the frequency of NKp44−NKG2A−double negative (DN) cells, a less-defined innate lymphoid cell population, decreased post-vaccination, but returned to pre-level post-infection. Post-vaccination DN cells (p = 0.042, r = −0.743) and IFN- γ+DN cells (p = 0.038, r = −0.755) negatively correlated with number of SIV challenges and positively correlated with chronic median VL (p = 0.046, r = 0.738) and peak VL (p = 0.001, r = 0.952), suggesting both cell populations might enhance SIV acquisition and contribute to viremia. No associations of circulating NK cells with protection were seen. Vaccines that promote mucosal NKp44+ cells and suppress DN cells are likely desirable.