Applied DNA Sciences (United States)

Candida species, including Candida albicans and Candida auris, represent a growing public health concern due to their increasing prevalence and resistance to antifungal agents. C. albicans is known for causing both superficial and invasive infections, while C. auris is a newly emerged, multidrug-resistant pathogen responsible for severe hospital outbreaks with a high mortality rate of ~ 60% in bloodstream infections. Vaccine candidates targeting C. albicans hyphal cell wall proteins Als3p and Hyr1p have shown protective efficacy in mice. NDV-3A, an alum-formulated Als3p-based vaccine, protects against recurrent vulvovaginal candidiasis in women. We earlier showed that both Als3p and Hyr1p have orthologs in C. auris, and that the NDV-3A vaccine, alongside an anti-Hyr1p monoclonal antibody, protect mice from lethal C. auris candidemia. Here, we optimized Als3p and Hyr1p dual antigen vaccine formulations with the clinical-stage adjuvant CAF01, demonstrating robust immunity and CD4 T celldependent protection against lethal C. albicans and C. auris. The vaccine formulations also showed enhanced protective efficacy when combined with antifungal drugs. This study highlights the potential of the CAF01-formulated Als3p/Hyr1p dual antigen vaccine in providing durable protective immunity against systemic and mucosal C. albicans and cross-protection against systemic multidrug-resistant C. auris infections.

ABSTRACTThe rapid development of mRNA vaccines since the COVID-19 pandemic has highlighted the potential of mRNA technology for vaccine and therapeutic applications. However, evaluating mRNA quality, including its integrity, 5′ capping efficiency, and 3′ poly(A) tailing, remains complex and challenging. Current analytical methods provide detailed insights, but are often limited by long analysis times, complex sample preparation, and the need for specialized expertise. The 5’ CapQassay addresses these challenges and provides a novel, rapid, and straightforward method that offers a single, unique measurement of intact mRNA with both a 5′cap and 3′poly(A) tail. This 2-hour benchtop-based assay provides quantitative or relative analysis, with high accuracy and precision without extensive sample processing. The 5’ CapQassay offers a significant advancement in mRNA analytics to alleviate bottlenecks in applications includingin vitrotranscription (IVT) reaction optimization, post-transcriptional capping optimization, and assessment of batch-to-batch IVT bioprocess consistency.

Đặt vấn đề: Hiện nay, titan dioxyd (TiO2) (E 171) đã được Cơ quan an toàn Thực phẩm châu Âu (EFSA) cấm sử dụng làm phụ gia thực phẩm. Việc giới hạn titan dioxyd trong một số phạm vi của sản xuất dược phẩm đang được xem xét. Nghiên cứu này nhằm đánh giá hiệu quả bảo vệ viên nhân tránh tác động ánh sáng của một số thành phần vô cơ. Qua đó hướng đến đề xuất một số tá dược tiềm năng thay thế titan dioxyd trong thành phần màng bao phim. Đối tượng và phương pháp nghiên cứu: Tiếp cận thiết kế thực nghiệm để nghiên cứu ảnh hưởng của loại, tỉ lệ tá dược vô cơ và mức tăng khối lượng của màng phim chứa TiO2, CaCO3, MgCO3 hoặc ZnO trên (1) độ nhớt dịch bao, (2) khả năng tạo đục, (3) độ bền ánh sáng của dược chất trong viên. Khả năng tương tác gây biến màu của tá dược tiềm năng trong màng phim cũng được đánh giá đối sánh với TiO2. Kết luận: Bên cạnh TiO2 hiện đã được sử dụng phổ biến, ZnO có thể được xem xét là một trong những tá dược tiềm năng. Dữ liệu nghiên cứu góp phần tạo cơ sở tham khảo và đa dạng hóa tiếp cận cho các nhà bào chế trong thiết kế thành phần công thức dịch bao phim viên nén. Từ khóa: titan dioxyd, kẽm oxyd, chống ánh sáng, bao phim, phim HPMC

indicam que a suplementao de vitamina D pode promover efeitos benficos.

Abstract DNA-based vaccines represent a simple, safe and promising strategy for harnessing the immune system to fight infectious diseases as well as various forms of cancer and thus are considered an important tool in the cancer immunotherapy toolbox. Nonetheless, the manufacture of plasmid DNA vaccines has several drawbacks, including long lead times and the need to remove impurities from bacterial cultures. Here we report the development of polymerase chain reaction (PCR)-produced amplicon expression vectors as DNA vaccines and their in vivo application to elicit antigen-specific immune responses in animal cancer models. Amplicons encoding tumor-associated-antigens, such as telomerase reverse transcriptase or neoantigens expressed by murine tumor cell lines were able to elicit antigen-specific immune responses and proved to significantly impact tumor growth when administered in combination with immune-checkpoint inhibitors (ICIs). These results strongly support the further exploration of the use of PCR-based amplicons as an innovative immunotherapeutic approach to cancer treatment.

The dissemination of IgA-dependent immunity between mucosal sites has important implications for mucosal immunoprotection and vaccine development. Epithelial cells in diverse gastrointestinal and nonintestinal mucosal tissues express the chemokine MEC/CCL28. Here we demonstrate that CCR10, a receptor for MEC, is selectively expressed by IgA Ab-secreting cells (large s/cIgA+CD38hiCD19int/–CD20–), including circulating IgA+ plasmablasts and almost all IgA+ plasma cells in the salivary gland, small intestine, large intestine, appendix, and tonsils. Few T cells in any mucosal tissue examined express CCR10. Moreover, tonsil IgA plasmablasts migrate to MEC, consistent with the selectivity of CCR10 expression. In contrast, CCR9, whose ligand TECK/CCL25 is predominantly restricted to the small intestine and thymus, is expressed by a fraction of IgA Ab-secreting cells and almost all T cells in the small intestine, but by only a small percentage of plasma cells and plasmablasts in other sites. These results point to a unifying role for CCR10 and its mucosal epithelial ligand MEC in the migration of circulating IgA plasmablasts and, together with other tissue-specific homing mechanisms, provides a mechanistic basis for the specific dissemination of IgA Ab-secreting cells after local immunization.

Recent literature regarding microarray technology has focused on the need to incorporate classical statistical practices in experimental design in order to utilize more robust, classical statistical methodologies in data analysis. We have demonstrated that classical statistical methods are applicable to analysis of data previously presented by Golub, et al. 1999. Our preliminary analysis of all 6817 genes involves simple t-tests for statistically significant separation of means of gene expression level in two cancer types. Our subsets of genes that distinguish AML types from ALL types are relatively consistent with those published by Golub. We select those predictor genes based on the t-values and stepwise discriminant analysis, and evaluate the resulting model’s performance in predicting 34 test samples by linear discriminant analysis. Only two samples were not correctly predicted (samples 61 and 66) with 25 predictor genes we chose. We also evaluate the parsimony of our model by evaluating, through a stepwise method, the minimum number of genes required to maintain a high level of accuracy in predicting cancer types.