Fig. 6: Targets associated with decreased risk and hypothetical mechanisms of vaccine efficacy.

a Heatmap summarizing the significant two-tailed Spearman correlations between the absolute levels (pg/ml) of epidermal growth factor (EGF), Interleukin 17 F (IL-17F), C-C motif chemokine ligand 8 (CCL8), C-X-C motif chemokine ligand 8 (CXCL8), and lymphotoxin-alpha (LTA) measured in plasma collected at week 12 + 24 h from ALFQA (n = 12) and alum (n = 17) animals, and at week 13 from ALFQA (n = 12) and alum (n = 12) animals, and time of acquisition (TOA). The ρ-values are identified by the color-scale, while the significant correlations (p < 0.05) are identified by asterisks. Reported p values are unadjusted for multiple comparisons. b, c Correlation of the absolute level (pg/ml) of plasma LTA at week 13 with b TOA in ALFQA (n = 12) or alum (n = 12) animals or c the vaccine-induced change (week 13 – baseline) of the frequency of rectal DC-10 in ALFQA (n = 12) animals (paired data not available in alum-treated animals). d Correlations of the absolute level (pg/ml) of plasma CCL8 at week 12 + 24 h with TOA in alum (n = 17) and ALFQA (n = 12) animals. e Schematic representation of immune responses contributing to vaccine efficacy at the systemic and mucosal levels and their comparison between ALFQA (left) and Alum (right) groups. In peripheral blood, the immunization with ΔV1DNA/ALVAC and ΔV1gp120 protein boost adjuvanted in ALFQA induces antibodies to gp120 mediating ADCC, and, when compared to Alum, higher ADCP and ADNP, together with higher CD14⁺ efferocytes. In the ALFQA group, vaccination induces higher levels of LTA and other cytokines/chemokines. LTA in plasma induces mucosal tolerogenic DC-10, toward a protective phenotype. Together with increased anti-inflammatory CD73⁺CD163⁺ macrophages and ILCs that express NKp44⁺ and maintain tissue-homeostasis, DC-10 favors the killing and clearance of SIV-infected apoptotic cells, preventing the recruitment of CD4⁺ target T cells. The figure contains images (monkeys and immunogens) created in BioRender. Woode, E. (2025) https://BioRender.com/p4mqsnf. Correlations: b–d two-tailed Spearman correlation with simple linear regression. Alum animals and correlations are depicted in blue, ALFQA animals and correlations are depicted in red. Source data are provided as a Source Data file.