Innate immune cell activation after HIV-1 vaccine administration is associated with increased antibody production

Abstract

The RV144 Thai phase III clinical trial's canarypox-protein HIV vaccine regimen showed modest efficacy in reducing infection. We therefore sought to determine the effects of vaccine administration on innate cell activation and subsequent associations with vaccine-induced immune responses. RV306 was a randomized, double-blind clinical trial in HIV-uninfected Thai adults that tested delayed boosting following the RV144 regimen. PBMC collected from RV306 participants prior to and 3 days after the last boost were used to investigate innate immune cell activation. Our analysis showed an increase in CD38+ mucosal associated invariant T (MAIT) cells, CD38+ invariant natural killer T (iNKT) cells, CD38+ γδ T cells, CD38+, CD69+ and HLA-DR+ NK cells 3 days after vaccine administration. An increase in CD14-CD16+ non-classical monocytes and CD14+CD16+ intermediate monocytes accompanied by a decrease in CD14+CD16- classical monocytes was also associated with vaccine administration. Inclusion of ALVAC-HIV in the boost did not further increase MAIT, iNKT, γδ T, and NK cell activation or increase the proportion of non-classical monocytes. Additionally, NK cell activation 3 days after vaccination was positively associated with antibody titers of HIV Env-specific total IgG and IgG1. Vδ1 T cell activation 3 days after vaccine administration was associated with HIV Env-specific IgG3 titers. Finally, we observed trending associations between MAIT cell activation and Env-specific IgG3 titers and between NK cell activation and TH023 pseudovirus neutralization titers. Our study identifies a potential role for innate cells, specifically NK, MAIT, and γδ T cells, in promoting antibody responses following HIV-1 vaccine administration.

Keywords: HIV vaccine; MAIT (mucosal-associated invariant T) cell; NK cell; gamma delta (γδ) T cells; iNKT cell; immune activation; monocytes.

Figure 1

Innate and T cell activation 3 days post vaccination. (A) MAIT, (B) iNKT, (C) Vδ1 T, (D) Vδ2 T cell, (E) conventional T cells and (F) NK cell activation pre- and post-vaccination. (G) Changes in monocyte frequency pre- and post-vaccination. Classical monocytes are defined as CD14+CD16-, intermediate monocytes as CD14+CD16+ and non-Classical monocytes are defined as CD14-CD16+. Groups 2 (ALVAC-HIV + AIDSVAX B/E) and 3 (AIDSVAX B/E) are combined for analysis (n=16).

Figure 2

Innate and T cell activation in RV306 study participants that received ALVAC-HIV and AIDSVAX B/E or AIDSVAX B/E alone. Activation of MAIT, iNKT, NK, γδ T cells, and conventional T cell was analyzed in 7 participants from group 2 (ALVAC-HIV + AIDSVAX B/E) and 9 participants from group 3 (AIDSVAX B/E).

Figure 3

Correlation between innate and T cell activation with adaptive immune responses 14 days post-vaccination. Heat map showing the Spearman R values for associations between immune activation at day 3 (Y axis) and adaptive immune responses at day 14 post vaccination (X axis). Significant and trending p-values are denoted on the heatmap. Classical monocytes are defined as CD14+CD16-, intermediate monocytes as CD14+CD16+ and non-Classical monocytes are defined as CD14-CD16+. All participants from group 2 and 3 were included in the heatmap analysis (n=16).