A solid-in-oil-in-water emulsion: An adjuvant-based immune-carrier enhances vaccine effect

The biomaterial-based immunoengineering has become one of the most attractive research fields in the last decade. In the present study, a solid-in-oil-in-water (S/O/W) emulsion encapsulating antigen in the oil phase of an oil-in-water (O/W) emulsion was prepared as a novel vaccine carrier consisting of similar materials to the emulsion adjuvant of which the safety, immunogenicity and vaccination efficacy have been already confirmed in human. Direct observation by high-resolution confocal laser scanning microscopy and small angle X-ray scattering analysis showed that the antigens were dispersed inside of the oil phase of the S/O/W emulsion as solid-state particles.

The S/O/W emulsion robustly produced antigen-specific antibodies and enhanced the antitumor effects in a therapeutic cancer vaccination compared with free antigens or the O/W emulsion in vivo. This result is in good agreement with the activation effect of antigen-specific cytotoxic T lymphocytes and antigen presentation by the S/O/W emulsion, indicating that the S/O/W emulsion consisting of already approved materials is a promising vaccine carrier to produce both humoral and cellular immunity.

CD38 ⁺ B cells affect immunotherapy for allergic rhinitis

Background: Allergen specific immunotherapy (AIT) is the mainstay in the treatment of allergic diseases. Yet the therapeutic effects of AIT need to be improved. CD38+ B cells are an immune cell fraction involving in the pathogenesis of allergic diseases as well as in the immune regulation.background OBJECTIVES: To elucidate the role of antigen specific CD38+ B cells in AIT.

An analysis was carried out on AIT results of 48 patients with perennial allergic rhinitis (AR), among which peripheral blood immune cells details are in joplink Corticosterone-BSA Conjugate which were analyzed by flow cytometry; serum cytokine levels were determined by ELISA. An AR murine model was developed to test the role of CD38+ B cells in AIT at the

A fraction of antigen-specific CD38+ B cell was detected in AR patients. CD38+ B cell frequency was negatively correlated with the therapeutic effects of AIT. A negative correlation was detected between the CD38+ B cell frequency and regulatory T cell frequency in AR patients treated with AIT. Exposure to specific antigens induced CD38+ B cells to produce IL-6, that converted Tregs to Th17 cells. Co-administration of anti-CD38 antibody significantly promoted the therapeutic effects of AIT.results CONCLUSIONS: Antigen-specific CD38+ B cells compromise the AIT effects by producing IL-6 to convert regulatory T cells to Th17 cells. Inhibition of CD38+ B cells promotes the effects of AIT.

Recall response to COVID-19 antigen is preserved in people with multiple sclerosis on anti-CD20 medications – A pilot study

Antibody responses to SARS-CoV-2 vaccination are impaired in people with multiple sclerosis (MS) under anti-CD20 therapies. It is however unclear, whether patients who received the basic immunization prior to anti-B cell medication start respond to the COVID-19 booster dose, once B cells are depleted.

To investigate the humoral response to recall antigen by COVID-19 booster vaccines in people with MS (pwMS), who recently started an anti-CD20 therapy compared to people with long-term B cell depletion.

We enrolled 15 pwMS who had received booster vaccination on anti-CD20 therapy. Of these, 11 had established anti-CD20 medications and were therefore vaccinated during a continuous state of B cell depletion (CD20-vaccine cohort). Four pwMS had received the basic immunization prior to anti-CD20 therapy commencement and only the booster dose (vaccine-CD20-vaccine cohort) under conditions of B cell depletion. We assessed SARS-CoV-2 specific antibody responses after booster vaccination among both groups and evaluated accompanying B cell numbers and proportions from the peripheral circulation.

The booster dose of SARS-CoV-2 vaccination elicited measurable antibody responses in 18% of individuals from the CD20-vaccine cohort compared to 100% from the vaccine-CD20-vaccine cohort. Antibody-levels were significantly higher among patients from the vaccine-CD20-vaccine cohort compared to the CD20-vaccine cohort (mean 951.25 ± 1137.96 BAU/ml, vs mean 12.36 ± 11.94 BAU/ml; mean difference 938 BAU/ml (95% CI: 249-1629 BAU/ml), p <0.0001). Among the vaccine-CD20-vaccine cohort, the booster immunization led to augmentation of spike antibody levels in 75% despite concomitant B cell depletion, and values increased by 3.8 – 9.4-fold compared to basic immunization. We observed no correlation of B cell kinetics and SARS-CoV-2 antibody levels.

Our study suggests that antibody production to recall COVID-19 antigens is preserved in pwMS despite concomitant anti-CD20 therapy. If corroborated in bigger cohorts, this could have implications in the management of individuals about to start B cell medications.

Gospel of malignant Glioma: Oncolytic virus therapy

Glioma accounts for nearly 80% of all intracranial malignant tumors. It is a major challenge to society as it is causes to impaired brain function in many patients. Currently, gliomas are mainly treated with surgery, postoperative radiotherapy, and chemotherapy. However, the curative effects of these treatments are not satisfactory. Oncolytic virus (OV) is a novel treatment which works by activating the immune functions and inducing apoptosis of tumor cells.

The OV propagates indefinitely in the host cell, eventually leading to the death of host cell. Subsequently, a large number of antigens and signal molecules are released which exert antitumor immunity. Several preclinical and clinical studies have shown that G207, DNX2401, Zika and other viruses have important roles in malignant tumors. For example, these viruses can reduce the growth of tumor cells without causing severe complications.

However, the known OVs have not been clearly classified. Herein, we divided OVs into neurotropic and non-neurophilic OVs based on whether the OVs are naturally neurotropic or not. The therapeutic effects of each group were compared. Finally, challenges encountered in the clinical application of OVs in the treatment of malignant gliomas were summarized.

Unraveling B cell trajectories at single cell resolution

During adaptive immunity, B cells differentiate either into memory B cells or plasma cells and produce antibodies against foreign antigens to fight infection. Additionally, they behave as antigen-presenting cells and participate in T cell activation during cellular immune responses. However, their functional dysregulation can result in various autoimmune diseases and cancers.

With significant breakthroughs in single cell technologies, assessing individual B cell genomics, transcriptomics, and proteomics can give deeper insights into mammalian B cell development, differentiation, antibody repertoire, and responses under conditions of homeostasis, infection, and aberrations during disease. In this review, we discuss the adoption of single cell approaches to identify different B cell gene signatures and biomarkers in normal and diseased tissues, and subsequent benefits for future therapeutic discoveries.

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