The induction of T cell-mediated immunity is crucial in vaccine development. The most effective vaccine is likely to employ both cellular and humoral immune responses. The efficacy of a vaccine depends on T cells activated by antigen-presenting cells. T cells also play a critical role in the duration and cross-reactivity of vaccines. Moreover, pre-existing T-cell immunity is associated with a decreased severity of infectious diseases. Many technical and delivery platforms have been designed to induce T cell-mediated vaccine immunity. The immunogenicity of vaccines is enhanced by controlling the kinetics and targeted delivery. Viral vectors are attractive tools that enable the intracellular expression of foreign antigens and induce robust immunity. However, it is necessary to select an appropriate viral vector considering the existing anti-vector immunity that impairs vaccine efficacy. mRNA vaccines have the advantage of rapid and low-cost manufacturing and have been approved for clinical use as COVID-19 vaccines for the first time. mRNA modification and nanomaterial encapsulation can help address mRNA instability and translation efficacy. This review summarizes the T cell responses of vaccines against various infectious diseases based on vaccine technologies and delivery platforms and discusses the future directions of these cutting-edge platforms.
Background: Immune checkpoint inhibitors can cause various adverse effects. Recently it has been shown that Vogt–Koyanagi–Harada (VKH) disease-like uveitis can occur in patients treated with nivolumab. Case presentation: A 69-year-old man developed bilateral panuveitis after nivolumab treatment for recurrent hypopharyngeal cancer. Slit lamp examination revealed bilateral granulomatous keratic precipitates, anterior chamber cells and partial synechiae. Fundus examination revealed bilateral optic disc edema and diffuse serous retinal detachment. His human leukocyte antigen (HLA) typing showed HLA-DRB1*04:05 allele. A lumbar puncture did not demonstrate pleocytosis. Bilateral sub-tenon injections of triamcinolone acetonide were initiated. As his panuveitis did not regress completely, steroid pulse therapy was administered. That therapy led to the resolution of his serous retinal detachment and to rapid improvement in his vision. Following this, we treated him with 50 mg/day of prednisolone for 1 week and then reduced it by 5 mg every week. No bilateral uveitis relapse had occurred by his 3-month follow-up; however, he subsequently died because of his cancer. Conclusion: To our knowledge, this is the first report of a patient with NVKH who underwent a lumbar puncture. Unlike VKH, our case did not show meningismus or pleocytosis. NVKH may, therefore, have a different etiology from VKH. In cases of NVKH with posterior uveitis, steroid pulse therapy may be considered as a treatment option, as it is in VKH.
Objective: This research seeks to investigate the effects of preoperative intense pulsed light with manual meibomian expression (IPL-MGX) on the refractive accuracy of cataract surgery on dry eyes with meibomian gland dysfunction (MGD-related dry eyes). Methods: Fifty-six MGD-related dry eye cases planned for cataract surgery were analyzed. IPL-MGX (four times at 2-week intervals) was performed before preoperative examination. Axial length (AL), anterior chamber depth (ACD), corneal curvature (mean-K), tear break-up time (TBUT), superficial punctate keratopathy in the central cornea (C-SPK), corneal higher-order aberrations (HOAs), and predicted postoperative spherical equivalent (P-SE) were evaluated pre- and post-IPL-MGX. The postoperative subjective spherical equivalent (S-SE) was evaluated after one month. The absolute difference between the S-SE and P-SE was considered an indication of P-SE accuracy. Changes in all the variables were assessed before and after IPL-MGX treatment. Results: No significant differences were observed in AL or ACD (p = 0.85, 0.56). The differences in mean-K, TBUT, C-SPK, and HOAs were significant (p < 0.01). P-SE accuracy based on post-IPL-MGX data was significantly higher than that based on pre-IPL-MGX data (p < 0.01). P-SE accuracy was within 0.25 diopters (D) in 14.3% of pre- and 55.4% of post-IPL-MGX, within 0.5D in 55.4% of pre- and 92.9% of post-IPL-MGX, within 0.75D in 98.2% of pre- and post-IPL-MGX, and within 1.0D in 98.2% of pre- and 100% of post-IPL-MGX. In the range of 0.25 and 0.5 D, the accuracy of P-SE was significantly higher in post-IPL-MGX (p < 0.01). Conclusions: Preoperative IPL-MGX considerably improved the predicted postoperative refraction accuracy in patients with MGD-related dry eye undergoing cataract surgery.
Nocturnal and circadian intraocular pressure (IOP) fluctuations are important issues in glaucoma treatment. Ripasudil 0.4% eye drops, a new glaucoma medication, lowers IOP by increasing aqueous humor outflow through the trabecular meshwork. We aimed to compare differences between circadian IOP fluctuations measured using a contact lens sensor (CLS) before and after administering 0.4% ripasudil eye drops adjunctively to patients with primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG). Patients with POAG (n = 1) and NTG (n = 5) underwent 24 h IOP monitoring with a CLS before and after administering ripasudil eye drops every 12 h (8 a.m., 8 p.m.) for 2 weeks without discontinuing currently used glaucoma medications. No vision-threatening adverse event occurred. The reduction in IOP fluctuation and the reduction in the SD of IOP in 24 h, awake time and sleep time did not reach statistical significance. The baseline office-hour IOP, which was measured using Goldmann applanation tonometry (GAT), ranged in the low teens, and the reduction in office-hour IOP also did not show a significant difference. Further study is necessary to evaluate whether the low baseline IOP with less IOP reduction relates to attenuated IOP fluctuation reduction.
Sarcoidosis is a systemic inflammatory disease characterized by the formation of non-caseating granulomas, with varied clinical manifestations. The common etiology of sarcoidosis is uncertain, but it is thought to be triggered by an exogenous antigenic stimulus, such as some bacterial proteins. Toll-like receptors (TLRs) recognize microbial components and elicit innate as well as adaptive immune responses. It has been reported that polymorphisms in TLR2 might be important in a small group of Caucasian sarcoidosis patients. The present study aimed to establish whether these findings are relevant to the Japanese population. We genotyped 5 single-nucleotide polymorphisms (SNPs) in TLR2 and assessed the allelic diversity between 257 Japanese sarcoidosis patients and 193 Japanese healthy controls. No significant differences in the frequency of TLR2 alleles and haplotypes in the sarcoidosis cases were found in comparison with the controls. However, marginal associations were observed for TLR2 at rs3804099 and rs3804100 in sarcoidosis patients with cutaneous manifestations. Our results suggest that TLR2 polymorphisms are not significantly related to the pathogenesis of sarcoidosis in the Japanese population.
Objectives: To compare the effects of two preoperative dry eye treatments—3% diquafosol sodium (DQS) and intense pulsed light with meibomian gland expression (IPL-MGX)—on refractive accuracy in cataract surgery and identify tear break-up time (TBUT) thresholds predictive of refractive success. Methods: In this prospective, paired-eye study, 62 patients (124 eyes) with meibomian gland dysfunction underwent bilateral cataract surgery with the same trifocal intraocular lens. One eye received DQS, while the fellow eye underwent four IPL-MGX sessions before biometry. Postoperative absolute prediction error (P-SE) was compared. TBUT and higher-order aberrations (HOAs) were evaluated. Logistic regression identified predictors of refractive accuracy, and receiver operating characteristic (ROC) analysis assessed the predictive value of TBUT for P-SE thresholds of <0.25 D and <0.50 D. Results: P-SE was significantly lower in IPL-MGX–treated eyes than in DQS-treated eyes (mean paired difference −0.11 D, p < 0.001). Success rates within <0.25 D and <0.50 D were higher with IPL-MGX (p < 0.01). TBUT and HOAs were predictors in univariate models, but only TBUT remained significant in the multivariable analysis (odds ratio, 4.90 per 1-s increase; 95% confidence interval, 1.92–12.51; p < 0.001). ROC analysis supported TBUT cutoffs of 7 s (<0.25 D) and 6 s (<0.50 D). Conclusions: IPL-MGX may improve refractive accuracy compared to DQS. TBUT appeared to be the most consistent predictor, and achieving ≥6 s was associated with higher likelihood of refractive success.