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BackgroundAdjuvants are chemical or biological materials that enhance the efficacy of vaccines. A-910823 is a squalene-based emulsion adjuvant used for S-268019-b, a novel vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that is currently in clinical development. Published evidence has demonstrated that A-910823 can enhance the induction of neutralizing antibodies against SARS-CoV-2 in humans and animal models. However, the characteristics and mechanisms of the immune responses induced by A-910823 are not yet known.Methods and ResultsTo characterize A-910823, we compared the adaptive immune response profile enhanced by A-910823 with that of other adjuvants (AddaVax, QS21, aluminum salt-based adjuvants, and empty lipid nanoparticle [eLNP]) in a murine model. Compared with other adjuvants, A-910823 enhanced humoral immune responses to an equal or greater extent following potent T follicular helper (Tfh) and germinal center B (GCB) cell induction, without inducing a strong systemic inflammatory cytokine response. Furthermore, S-268019-b containing A-910823 adjuvant produced similar results even when given as a booster dose following primary administration of a lipid nanoparticle-encapsulated messenger RNA (mRNA-LNP) vaccine. Preparation of modified A-910823 adjuvants to identify which components of A-910823 play a role in driving the adjuvant effect and detailed evaluation of the immunological characteristics induced by each adjuvant showed that the induction of humoral immunity and Tfh and GCB cell induction in A-910823 were dependent on α-tocopherol. Finally, we revealed that the recruitment of inflammatory cells to the draining lymph nodes and induction of serum cytokines and chemokines by A-910823 were also dependent on the α-tocopherol component.ConclusionsThis study demonstrates that the novel adjuvant A-910823 is capable of robust Tfh cell induction and humoral immune responses, even when given as a booster dose. The findings also emphasize that α-tocopherol drives the potent Tfh-inducing adjuvant function of A-910823. Overall, our data provide key information that may inform the future production of improved adjuvants.

Additional file 2: Supplementary Fig. S1. Kaplan–Meier curves for progression-free survival (PFS). Supplementary Fig. S2. Analysis of chemokines and cytokines. Supplementary Fig. S3. Gating strategy for immune phenotyping and functional characteristics of T cells. Supplementary Fig. S4. Foxp3 expression in effector memory of CD4+ T cells in individual cases.

Additional file 1: Supplementary Table S1. Adverse Events. Supplementary Table S2. Immune phenotypes of CD4+ and CD8+ T cells.

Additional file 1. Modified Japanese Orthopaedic Association (JOA) scoring system for lumbar function.

Background: Deep venous thrombosis (DVT) and pulmonary embolism are serious potential complications after anterior cruciate ligament reconstruction (ACLR). Little is known about the influence of tourniquet use on the incidence of DVT after ACLR. Purpose: To compare the incidence of DVT after ACLR with and without the use of a tourniquet. Study Design: Cohort study; Level of evidence, 3. Methods: Between November 2018 and May 2020, a total of 60 consecutive ACLRs in 60 patients, including 7 revision surgeries, were performed without tourniquet use at our hospital and were enrolled in this study (T– group). In addition, 55 consecutive ACLRs in 55 patients, including 10 revision surgeries, were performed with tourniquet use between April 2017 and September 2018 and were enrolled as the control group (T+ group). DVT was diagnosed using ultrasonography of both legs performed preoperatively and at postoperative week 1. The incidence of postoperative DVT was compared between the T– and T+ groups. Logistic regression analysis was performed to evaluate the effect of older age (≥40 vs Results: No DVTs were detected preoperatively. The incidence of postoperative DVT was significantly lower in the T– group compared with the T+ group (1 patient [1.7%] vs 9 patients [16.4%]; P = .005). All patients with DVT were asymptomatic. Although the mean operative time was not significantly different (80.8 minutes in the T+ group vs 78.5 minutes in the T– group; P = .461), the mean blood loss from the drain was significantly lower in the T– group than in the T+ group (149.9 vs 201.9 mL; P < .001). Age ≥40 years and tourniquet use were significantly related to the occurrence of DVT (odds ratio, 8.3 [95% CI, 1.9-36.8]; P = .005; and odds ratio, 8.8 [95% CI, 1.0-75.3]; P = .047, respectively). Conclusion: ACLRs performed without tourniquet resulted in a significantly lower incidence of DVT after ACLR and significantly less bleeding from drains. If adequate visibility of the surgical field is obtained, ACLR without tourniquet use may reduce the incidence of DVT.

BACKGROUND:There have been no reports describing how cervical reconstruction surgery affects global spinal alignment (GSA). OBJECTIVE:To elucidate the effects of cervical reconstruction for GSA through a retrospective multicenter study. METHODS:Seventy-eight patients who underwent cervical reconstruction surgery for cervical kyphosis were divided into a Head-balanced group (n=42) and a Trunk-balanced group (n=36) according to the values of the C7 plumb line (PL). We also divided the patients into a cervical sagittal balanced group (CSB group, n=18) and a cervical sagittal imbalanced group (CSI group, n=60) based on the C2 PL-C7 PL distance. Various sagittal Cobb angles and the sagittal vertical axes were measured before and after surgery. RESULTS:Cervical alignment was improved to achieve occiput-trunk concordance (the distance between the center of gravity [COG] PL, which is considered the virtual gravity line of the entire body, and C7 PL&nbsp

The assessment Scale Proposed by the Japanese Orthopaedic Association. The Japanese Orthopaedic Association Scoring system (JOA score) consists of 2 categories (subjective and objective symptoms), ranging from 0 (worst condition) to 15 (best condition). (DOCX 22 kb)

is Figure S2 showing treatment of MAPK inhibitors to AF cells with ROS. Real-time RT-PCR analysis of the expression of TNFα and MMP-3 in AF cells. MAPK signaling inhibitors, including p38 inhibitor (SB), JNK inhibitor (SP), and ERK inhibitor (PD), were treated to AF cells with H2O2 (upper) or BSO (lower). Data presented as mean ± SD of three independent experiments performed in triplicate (n = 3); *p

is Figure S1 showing molecular phenotype of the passaged rat AF cells. Real-time RT-PCR analysis of the mRNA expression of type I collagen, type II collagen, and aggrecan in the second (P2) and fifth (P5) passaged AF cells. Data presented as mean ± SD of three independent experiments performed in triplicate (n = 3); *p

Few of the vaccines in current use can induce antigen- (Ag-) specific immunity in both mucosal and systemic compartments. Hence, the development of vaccines that realize both mucosal and systemic protection against various pathogens is a high priority in global health. Recently, it has been reported that intramuscular (i.m.) vaccination of an adenovirus vector (Adv) can induce Ag-specific cytotoxic T lymphocytes (CTLs) in both systemic and gut mucosal compartments. We previously revealed that type I IFN signaling is required for the induction of gut mucosal CTLs, not systemic CTLs. However, the molecular mechanism via type I IFN signaling is largely unknown. Here, we report that type I IFN signaling following i.m. Adv vaccination is required for the expression of type I IFN in the inguinal lymph nodes (iLNs), which are the draining lymph nodes of the administration site. We also showed that the type I IFN signaling is indispensable for the early activation of CTLs in iLNs. These data suggested that type I IFN signaling has an important role in the translation of systemic innate immune response into mucosal adaptive immunity by amplifying the innate immune signaling and activating CTLs in the iLN.