Preclinical specificity & activity of a fully human 41BB-expressing anti-CD19 CART- therapy for treatment-resistant autoimmune disease.

Over 4% of the global population is estimated to live with autoimmune disease, necessitating immunosuppressive treatment that is often chronic, not curative, and carries associated risks. B cells have emerged as key players in disease pathogenesis, as evidenced by partial responsiveness to B cell depletion by antibody-based therapies. However, these treatments often have transient effects due to incomplete depletion of tissue-resident B cells.

Peripheral CD4 T follicular cells induced by a conjugated pneumococcal vaccine correlate with enhanced opsonophagocytic antibody responses in younger individuals.

Background: PCV13 (conjugated polysaccharide) and PPSV23 (polysaccharide only) are two licensed vaccines targeting S. pneumoniae. The role of CD4 T-cell responses in pneumococcal vaccines among healthy participants and their impact on antibodies is not yet known.

Antisense-Derived HIV-1 Cryptic Epitopes Are Not Major Drivers of Viral Evolution during the Acute Phase of Infection.

While prior studies have demonstrated that CD8 T cell responses to cryptic epitopes (CE) are readily detectable during HIV-1 infection, their ability to drive escape mutations following acute infection is unknown. We predicted 66 CE in a Zambian acute infection cohort based on escape mutations occurring within or near the putatively predicted HLA-I-restricted epitopes. The CE were evaluated for CD8 T cell responses for patients with chronic and acute HIV infections.

A Novel Vaccine Approach for Chagas Disease Using Rare Adenovirus Serotype 48 Vectors.

Due to the increasing amount of people afflicted worldwide with Chagas disease and an increasing prevalence in the United States, there is a greater need to develop a safe and effective vaccine for this neglected disease. Adenovirus serotype 5 (Ad5) is the most common adenovirus vector used for gene therapy and vaccine approaches, but its efficacy is limited by preexisting vector immunity in humans resulting from natural infections. Therefore, we have employed rare serotype adenovirus 48 (Ad48) as an alternative choice for adenovirus/Chagas vaccine therapy.

Enhanced Recognition of HIV-1 Cryptic Epitopes Restricted by HLA Class I Alleles Associated With a Favorable Clinical Outcome.

Background: Cryptic epitopes (CEs) are peptides derived from the translation of 1 or more of the 5 alternative reading frames (ARFs; 2 sense and 3 antisense) of genes. Here, we compared response rates to HIV-1-specific CE predicted to be restricted by HLA-I alleles associated with protection against disease progression to those without any such association.

Methods: Peptides (9mer to 11mer) were designed based on HLA-I-binding algorithms for B*27, B*57, or B*5801 (protective alleles) and HLA-B*5301 or B*5501 (nonprotective allele) in all 5 ARFs of the 9 HIV-1 encoded proteins.

CD5 enhances Th17-cell differentiation by regulating IFN-γ response and RORγt localization.

Mechanisms that modulate the generation of Th17 cells are incompletely understood. We report that the activation of casein kinase 2 (CK2) by CD5 is essential for the efficient generation of Th17 cells in vitro and in vivo. In our study, the CD5-CK2 signaling pathway enhanced TCR-induced activation of AKT and promoted the differentiation of Th17 cells by two independent mechanisms: inhibition of glycogen synthase kinase 3 (GSK3) and activation of mTOR.

The POSH/JIP-1 scaffold network regulates TCR-mediated JNK1 signals and effector function in CD8(+) T cells.

Signals from the T-cell recognition of antigen program effector functions are necessary to clear infections and tumors. The JNK pathway is critically important in regulating this process. In T lymphocytes, JNK1 and JNK2 have distinct functions depending on their maturation state and cell-type.