Inactivated Herpes Simplex Virus (HSV-2, MS)

Silver nanoparticles (AgNPs) are promising novel antimicrobial agents for combating a wide range of skin and mucosal pathogens. However, their interactions with the immune system are currently not fully understood. Dendritic cells (DCs) are crucial in the development of T cell-specific responses against bacterial and viral pathogens. Tannic acid-modified silver nanoparticles (TA-AgNPs) have previously been shown to be a promising microbicide against Herpes Simplex Virus (HSV-2). This study aimed to compare the ability of TA-AgNPs or TA-AuNPs of similar sizes (TA-Ag/AuNPs) to induce DCs maturation and activation in the presence of HSV-2 antigens when used at non-toxic doses. Here, the researchers found that both TA-AgNPs and TA-AuNPs were efficiently internalized by DCs and induced activated ultrastructures. Although TA-AgNPs were more toxic than TA-AuNPs of corresponding size, they also stimulated DC maturation and TLR9 expression more effectively. TA-Ag/AuNPs-HSV-2 helped overcome the inhibition of dendritic cell maturation by live or inactivated virus by upregulating the expression of MHC II and CD86 and downregulating the expression of CD80. The downregulation of CD40 expression in HSV-2-infected dendritic cells was reversed when HSV-2 was treated with TA-NPs with a size >30 nm. On the other hand, small-sized TA-AgNPs facilitated better internalization of HSV-2 antigens. HSV-2 treated with both types of NPs stimulated the activation of JAWS II and memory CD8+ T cells, while TA-AgNPs treatment induced IFN-γ-producing CD4+ and CD8+ T cells. These studies suggest that TA-AgNPs or TA-AuNPs are good dendritic cell (DC) activators, although their ultimate effects on maturation and activation may depend on the metal and size. Therefore, TA-Ag/AuNPs constitute a new class of nanoadjuvants that help overcome virus-induced inhibition of DC activation.

Previous studies have shown that preincubation of HSV-2 inoculum with 2.5 µg/ml TA-NPs for 1 h completely inhibited infection in vitro. Here, researchers examined whether TA-NPs-treated HSV-2 (HSV) could induce DC maturation. First, the uptake level of TA-NPs-treated HSV-2 (NPs-HSV) by JAWS II cells was investigated and compared with non-treated HSV-2 and heat-inactivated HSV-2 (inHSV) (Figure 8A). The antigen uptake after 6 h post infection (p. i.) for HSV and inHSV was observed at the similar level (578.84 ± 15.67 MFI and 541.06 ± 60.78 MFI, respectively). Incubation of JAWS II with 2.5 µg/ml TA-NPs-HSV for 6 h significantly increased the internalization of viral antigens in the presence of S and M AgNPs-HSV compared with the HSV-2 infected control. The highest antigen uptake was observed for S TA-AgNPs-HSV (809.89 ± 21.79 MFI) (Figure 1). Blocking of the viral surface by L TA-AgNPs and all tested TA-AuNPs did not affect the uptake of viral antigens compared to untreated HSV-2 infection.

Figure 1. Presence of HSV-2 antigens in JAWS II cells after 6 h exposure to HSV-2, inactivated HSV-2, or NPs-treated HSV-2. (Orlowski P, et al., 2018)