TeloB-VAX

The vaccine development strategies have evolved from using an entire organism as an immunogen to a single antigen and further towards an epitope. Since an epitope is a relatively tiny and immunologically relevant part of an antigen, it has the potential to stimulate more robust and specific immune responses while causing minimal adverse effects. As a result, the recent focus of vaccine development has been to develop multi-epitope vaccines that can target multiple virulence mechanisms. Accordingly, we designed multi-epitope vaccine candidates B (multi-B-cell epitope immunogen) and CTB-B (an adjuvant - cholera toxin subunit B (CTB) - attached to immunogen B) against S. aureus by employing immunoinformatics approaches. The designed vaccines are composed of B-cell epitope segments (20-mer) of the eight well-characterized S. aureus virulence factors, namely ClfB, FnbpA, Hla, IsdA, IsdB, LukE, SdrD, and SdrE connected in series. The designed vaccines were expressed, purified, and administered to C57BL/6 mice with Freund adjuvant to evaluate the immunogenicity and protective efficacy. The results revealed that the immunized mice showed high IgG titers for the immunogen, and the antibody titers increased significantly following the second immunization. However, the generated antibodies did not protect the mice from infection. The interaction of anti-B antibodies with source virulence factors showed that the generated antibodies have no binding affinity with any of the corresponding virulence factors. Our results demonstrate the limitation of the in silico designed B-cell multi-epitope vaccine and suggest that a protein domain carrying both linear and conformational B-cell epitopes might be a better choice for developing an effective multi-epitope vaccine against S. aureus.

Systemic lupus erythematosus (SLE) is an autoimmune disease that involves multiple organ systems. Due to the heterogeneity of its presentation, it is challenging for clinicians to diagnose and manage the symptoms. SLE has a wide range of presentations from mild to severe and involves various organ systems like mucocutaneous, musculoskeletal, cardiopulmonary, renal, gastrointestinal, and central nervous system. Various novel treatment modalities are being used based on clinical presentation. Prednisone and methylprednisolone are commonly used as needed for acute flares of SLE. Some patients may need a low dose of oral prednisone to keep their SLE under control, which carries a risk of coronary artery disease (CAD) and many other metabolic side effects of steroids. Other long-term medications that are commonly used include hydroxychloroquine, methotrexate, azathioprine, mycophenolate, cyclosporine, and cyclophosphamide. Intravenous cyclophosphamide is used only in severe lupus with renal, pulmonary, or CNS involvement. Rituximab is a human monoclonal B-cell cluster of differentiation (CD)20 receptor antibody used for severe SLE not responding with other medications. Other newer medications are belimumab and anifrolumab. Anifrolumab is a fully human monoclonal antibody that binds to subunit 1 of the type I interferon receptor. We present a case of a 25-year-old female with a chronic history of SLE presented to the outpatient clinic with abdominal distension that needed frequent abdominal paracenteses. She was using hydroxychloroquine, mycophenolate mofetil, and prednisone, but her symptoms were not adequately controlled. After we started the patient on monthly intravenous belimumab, her symptoms and the frequency of visits for paracentesis gradually reduced. B-cells are known to play an essential role in the pathogenesis of SLE, and the use of belimumab, an anti-BLys (B-lymphocyte stimulator) human monoclonal antibody that inhibits B-cell growth, can play a significant role in the management of SLE associated chronic serositis.