Immune escape and waning immunity of COVID-19 monovalent mRNA vaccines against symptomatic infection with BA.1/BA.2 and BA.5 in Japan.

BACKGROUND: Repeated emergence of variants with immune escape capacity and waning immunity from vaccination are major concerns for COVID-19. We examined whether the surge in Omicron subvariant BA.5 cases was due to immune escape or waning immunity through vaccine effectiveness (VE) evaluation. METHODS: A test-negative case-control study was conducted in 16 clinics/hospitals during the BA.1/BA.2-dominant and BA.5-dominant periods. VE against symptomatic infection was estimated after adjusting for age, sex, comorbidity, occupation, testing frequency, prior infection, close contact history, clinic/hospital, week, and preventive measures. Absolute VE (aVE) was calculated for 2/3/4 doses, compared to the unvaccinated. Relative VE (rVE) was calculated, comparing 3 vs 2 and 4 vs 3 doses. RESULTS: 13,025 individuals were tested during the BA.1/BA.2-dominant and BA.5-dominant periods with similar baseline characteristics. For BA.1/BA.2, aVE was 52 % (95 %CI:34-66) 14 days-3 months post-dose 2, 42 % (29-52) > 6 months post-dose 2, 71 % (64-77) 14 days-3 months post-dose 3, and 68 % (52-79) 3-6 months post-dose 3. rVE was 49 % (38-57) 14 days-3 months post-dose 3 and 45 % (18-63) 3-6 months post-dose 3. For BA.5, aVE was 56 % (27-73) 3-6 months post-dose 2, 32 % (12-47) > 6 months post-dose 2, 70 % (61-78) 14 days-3 months post-dose 3, 59 % (48-68) 3-6 months post-dose 3, 50 % (29-64) > 6 months post-dose 3, and 74 % (61-83) ≥ 14 days post-dose 4. rVE was 56 % (45-65) 14 days-3 months post-dose 3, 39 % (27-48) 3-6 months post-dose 3, 25 % (-2-45) > 6 months post-dose 3, and 30 % (-6-54) ≥ 14 days post-dose 4. CONCLUSIONS: Booster doses initially provided high protection against BA.5 at a level similar to that against BA.1/BA.2. However, the protection seemed shorter-lasting against BA.5, which likely contributed to the surge. Furthermore, rVE post-dose 4 was low even among recent vaccinees. These results support the introduction of variant-containing vaccines and emphasize the need for vaccines with longer duration of protection.

Effectiveness of BA.1- and BA.4/BA. 5-Containing Bivalent COVID-19 mRNA Vaccines Against Symptomatic SARS-CoV-2 Infection During the BA.5-Dominant Period in Japan.

In this multicenter, prospective, test-negative, case-control study in Japan, the effectiveness of both BA.1-containing and BA.4/BA.5-containing bivalent coronavirus disease 2019 mRNA vaccines against symptomatic infection during the BA.5-dominant period was high compared with no vaccination (65% and 76%) and moderate compared with monovalent vaccines administered over half a year earlier (46% combined).

Improvement of dewatering characteristics by co-digestion of rice straw with sewage sludge.

A continuous mesophilic co-digestion of sewage sludge and softened rice straw was conducted and the dewatering characteristics of digested sludge were evaluated by a dewatering experiment using a belt press. The digestion was operated with solid retention time (SRT) of 25 days, and the feeding ratio of sludge to rice straw was 1:0.5 (total solids base). After 129 days of stable operation, the properties of digested sludge were analysed; then five kinds of cationic coagulants were tested to select the optimal coagulants for dewatering, and two coagulants were selected and used in the dewatering experiment because of lower doses and lower moisture of sludge cakes. Sludge property analysis showed that by the addition of rice straw, the fibrous materials in the digested sludge increased remarkably and the normalized capillary suction time (CST) decreased significantly, indicating that the dewatering properties was improved. The results of dewatering experiment showed that by the addition of rice straw, specific filtration rate of digested sludge increased by 81.2% and 174.6%, respectively; water content of dewatered sludge cakes decreased by 8.2% and 13.4%, respectively. The dewaterability of digested sludge was suggested to be improved due to rice straw addition.

[Toward therapeutic application of IL-10-producing regulatory T cells].

IL-10 is an anti-inflammatory cytokine with an important role in preventing inflammatory and autoimmune responses. IL-10 is also important for suppressive function of inducible regulatory T (iTreg) cells, several types of which were reported in succession. Type1 regulatory T (Tr1) cell is a representative of IL-10-prroducing regulatory T cells. Although specific surface markers or origin of Tr1 cells have not fully been clarified yet, IL-27 was recently reported to induce IL-10 production in T cells and be an inducer of Tr1 cells. We previously reported that CD4(+)CD25(-)lymphocyte activation gene (LAG-3)(+) Treg (LAG3(+) Treg) is one of the peripherally inducible Tregs and functions as an immune-regulator through IL-10 production. We found that the expression level of Egr-2, a transcription factor required for T cell anergy induction, is elevated in LAG3(+) Treg and that forced expression of Egr-2 induces LAG-3 expression and IL-10 production. Egr-2 has been suggested to be a key player of regulatory function in LAG3(+) Treg. In this study, we review Tr1 cells and the mechanism of IL-10 induction by IL-27 in T cells. Also, we introduce LAG3(+) Treg and discuss the therapeutic potential of these regulatory T cells.

Egr-2 transcription factor is required for Blimp-1-mediated IL-10 production in IL-27-stimulated CD4+ T cells.

Interleukin-27 (IL-27) suppresses immune responses through inhibition of the development of IL-17 producing Th17 cells and induction of IL-10 production. We previously showed that forced expression of early growth response gene 2 (Egr-2), a transcription factor required for T-cell anergy induction, induces IL-10 and lymphocyte activation gene 3 expression and confers regulatory activity on CD4(+) T cells in vivo. Here, we evaluated the role of Egr-2 in IL-27-induced IL-10 production. Among various IL-10-inducing factors, only IL-27 induced high levels of Egr-2 and lymphocyte activation gene 3 expression. Intriguingly, IL-27 failed to induce IL-10 in Egr-2-deficient T cells. IL-27-mediated induction of Prdm1 that codes B lymphocyte induced maturation protein-1, a transcriptional regulator important for IL-10 production in CD4(+) T cells, was also impaired in the absence of Egr-2. Although IL-27-mediated IL-10 induction was dependent on both STAT1 and STAT3, only STAT3 was required for IL-27-mediated Egr-2 induction. These results suggest that IL-27 signal transduction through Egr-2 and B lymphocyte induced maturation protein-1 plays an important role in IL-10 production. Furthermore, Egr-2-deficient CD4(+) T cells showed dysregulated production of IFN-γ and IL-17 in response to IL-27 stimulation. Therefore, Egr-2 may play key roles in controlling the balance between regulatory and effector cytokines.