SARS-CoV-2 mRNA booster vaccines provide protection from severe disease, eliciting strong immunity that is further boosted by previous infection. However, it is unclear whether these immune responses are affected by the interval between infection and vaccination. Over a 2-month period, we evaluated antibody and B cell responses to a third-dose mRNA vaccine in 66 individuals with different infection histories. Uninfected and post-boost but not previously infected individuals mounted robust ancestral and variant spike-binding and neutralizing antibodies and memory B cells. Spike-specific B cell responses from recent infection (<180 days) were elevated at pre-boost but comparatively less so at 60 days post-boost compared with uninfected individuals, and these differences were linked to baseline frequencies of CD27lo B cells. Day 60 to baseline ratio of BCR signaling measured by phosphorylation of Syk was inversely correlated to days between infection and vaccination. Thus, B cell responses to booster vaccines are impeded by recent infection.
Published by Elsevier Inc.

Curcumin is known to have immune-modulatory and antitumor effects by interacting with more than 30 different proteins. An important feature of curcumin is the inhibition of nuclear factor kappa of activated B-cells (NF-κB). Here, we evaluate the potential of curcumin to reverse the epithelial to mesenchymal transition (EMT) of head and neck squamous cell carcinoma (HNSCC) cells as a part of tumor escape mechanisms. We examined the impact of curcumin on the expression of different pro- and antitumoral chemokines in ex vivo HNSCC tumor tissue and primary macrophage cultures. Further, we evaluated the combinatorial effect of curcumin and toll-like receptor 3 (TLR3) agonist Poly I:C (PIC) on NF-κB inhibition and regulatory T-cell (Treg) attraction. Mesenchymal markers were significantly reduced in cancer specimens after incubation with curcumin, with simultaneous reduction of key transcription factors of EMT, Snail, and Twist. Furthermore, a decrease of the Treg-attracting chemokine CCL22 was observed. Additionally, curcumin-related inhibition of NF-κB nuclear translocation was evident. The combination of PIC with curcumin resulted in further NF-κB inhibition, whereas PIC alone contrarily resulted in NF-κB activation. Furthermore, curcumin was more effective in inhibiting PIC-dependent NF-κB activation and Treg attraction compared to known NF-κB inhibitors BAY 11-7082 or caffeic acid phenethyl ester (CAPE). The presented results show, for the first time, the immune-modulating effects of curcumin in HNSCC, with potent inhibition of the Treg-attracting effects of PIC. Hence, curcumin presents a promising drug in cancer therapy as a supplement to already established treatments.