Mucosal vaccine efficacy against intrarectal SHIV is independent of anti-Env antibody response

Myeloid Cell-Mediated Trained Innate Immunity in Mucosal AIDS Vaccine Development

“…Vaccari et al found that hypoxia and inflammasome activation in CD14+CD16-monocytes are correlates of decreased risk of SIV acquisition after vaccination with DNA/ALVAC/gp120 platform in macaques (25,27). We demonstrated in the macaques vaccinated with MVA/FLSC (fulllength single chain recombinant gp120 fused with two domains of CD4 to maintain the CD4-induced conformation) with complex adjuvants that reduced infection risk was achieved in the absence of protective antibody responses against HIV envelope (26). The protection correlated with CD14+DR-monocytes induced by the vaccine; but not the viral-specific T cell responses induced by the vaccine.…”

“…Recently, we and others found evidence that myeloid cellmediated trained immunity might be involved in mediating protection using similar immunization protocols like RV144 in macaque models (25)(26)(27). Vaccari et al found that hypoxia and inflammasome activation in CD14+CD16-monocytes are correlates of decreased risk of SIV acquisition after vaccination with DNA/ALVAC/gp120 platform in macaques (25,27).…”

“…As adjuvants, TLR agonists enhanced the potency of vaccine-induced adaptive immunity. Ten TLRs have been identified in humans, and most of them, such as TLR, 2, 3, 4, 7, 8, and 9 agonists, have been tested as adjuvants in HIV/SIV vaccine studies (26,(32)(33)(34)(35)(36). In these studies, TLR agonists promoted efficient vaccine antigen delivery, induced more pronounced cell activation, and increased T follicular helper cell differentiation and germinal center formation, which led to stronger antigen-specific T cell and antibody immune responses.…”

“…To develop a mucosal HIV/SIV vaccine, TLR2/6 agonist FSL-1 and MVA have been used as an adjuvant/delivery vector (26,32). It is interesting to investigate the functionality of the monocyte/macrophages differentiated from FSL-1-primed HSC/HPC, especially when the signaling pathways through TLR1/2 and TLR2/6 had opposite roles to either silence or boost the immune responses (85).…”

“…The macrophages showed an M2-like phenotype, and reduced their responses to LPS (100). Dietary changes also impact the gut microbiome, which has been shown to be associated with immune activation as well as HIV/SIV vaccine efficacy and susceptibility to infection (26,101). In this context, western diet, or insulin signaling/insulin resistance signals have been viewed as modulators of trained immunity (98,100,102).…”