China
Africa
Explore chapters and articles related to this topic
Immunomodulation of Cytokines and T Cells by Biologicals in Rheumatoid Arthritis
Published in Thomas F. Kresina, Immune Modulating Agents, 2020
Ravinder N. Maini, Marc Feldmann
Since even the best therapeutic approaches available thus far appear to offer only temporary control of symptoms, it is necessary to devise new strategies of treatment for a cure of RA. If this aim requires repeated therapy, then the potential immunogenicity of the biologicals becomes an issue that could limit their use. Two alternative approaches are immediately apparent: The first is to devise methods for reducing the immunogenicity of the biological and/or suppressing the immune response of the recipient. The second is to develop a chemical drug that simulates the effect of the biological by the advanced methods now available in the pharmaceutical industry. Our prediction is that both approaches will eventually be tried in practice, but current biologicals have a lead in this process. However, the ease of administration of chemical drugs (by mouth rather than injection) offers advantages, as does the likely lower cost to the consumer.
Neurological events following immunizations
Published in Avindra Nath, Joseph R. Berger, Clinical Neurovirology, 2020
There are several important determinants of vaccine efficacy, which modulate the intensity of peak antibody responses. The nature of the vaccine antigen and its intrinsic immunogenicity are important, with some antigens being inherently more immunogenic than others. Live vaccines generally elicit stronger innate immune responses and thus stronger antibody responses. Non-live vaccines frequently require the use of adjuvants, or agents which increase the stimulation of the immune system by enhancing antigen presentation; aluminum salts are frequently used as adjuvants [18]. Many vaccines, particularly inactivated vaccines, require multiple doses to induce high and sustained antibody responses, or may require repeated administration at particular intervals. Antibody persistence is critically important; for the vaccine immune response to last, memory B cells, which are capable of recognizing and responding to an antigen challenge and subsequently proliferating and differentiating into antibody producing plasma cells, must be produced. Antibody persistence may be dependent on several different determinants, including the nature of the vaccine (live vs. inactivated), interval between doses, and age at immunization.
Recombinant and modified vaccines and adjuvants used for allergen immunotherapy
Published in Richard F. Lockey, Dennis K. Ledford, Allergens and Allergen Immunotherapy, 2020
Jeffrey Stokes, Thomas B. Casale
Novel agents are being developed to treat allergic diseases based on expanding knowledge of innate and adaptive responses of the immune system on a molecular level. Allergen immunotherapy (AIT) is the only form of immunomodulation shown to induce immune tolerance for allergic diseases that persists after its discontinuation. There is also the potential benefit to prevent new sensitization to additional aeroallergens and to prevent asthma in high-risk children. Despite the benefits of AIT, improvement is not universal, and there is the risk of severe adverse reactions. Immunomodulators and novel forms of immunotherapy, which may be safer and more effective, are being developed to hopefully improve immunogenicity without increasing allergenicity. Novel forms of AIT seek to lessen the TH2 responses to allergens by altering the allergen vaccine or changing the mode by which the allergen vaccine is delivered. Other approaches include the use of adjuvants or vaccines that are nonallergen specific, such as toll-like receptor ligands (Figure 30.1 and Table 30.1).
A review of the DTaP-IPV-HB-PRP-T Hexavalent vaccine in pediatric patients
Published in Expert Review of Vaccines, 2023
Andrew Dakin, Ray Borrow, Peter D. Arkwright
A post-licensure commitment of DT2aP-IPV-Hib-HBV was to evaluate the primary series, antibody persistence, and booster response in those who are HIV positive. A phase III, open-label, randomized study was performed at a single center in the Republic of South Africa [50]. DT2aP-IPV-Hib-HBV was administered to HIV-exposed infected (Group A: N = 14) and HIV-exposed uninfected (Group B: N = 50) infants as a 6, 10, 14 week primary series with a toddler booster at 15–18 months of age. Immunogenicity of each antigen was measured using validated assays. In each group, primary series and booster immune seroprotection rates were strong, and pre-booster antibody persistence was good, although anti-HepB ≥10 mIU/mL in Group A was 78.6% post-primary series, 58.3% pre-booster, and 75.0% post-booster.
Adaptation of an ELISA assay for detection of IgG2a responses against therapeutic monoclonal antibodies in a mouse immunization model
Published in Journal of Immunotoxicology, 2022
Shraddha S Rane, Rebecca J Dearman, Ian Kimber, Jeremy P Derrick
In the current investigation, it was noted that the ELISA detection system used plays a crucial role in the experimental outcome and conclusions derived. The epitopes identified by the commercially-available detection antibodies have the potential for cross-reactivity with the ELISA substrate due to the exposed epitopes; the blocking reagents used also play important roles in preventing nonspecific binding of antigen and antibodies to microtiter plates as described previously (Chart et al. 1998). Assays utilized to assess and characterize immunogenicity should be designed to be sensitive and specific for the intended purpose. Appropriate experimental design, reagents used, and timepoints should be determined along with recommendations for an assay procedure, when needed, to detect meaningful antibody responses at pre-clinical and clinical stages in the development of ELISA assays using therapeutic mAb.
Assay format diversity in pre-clinical immunogenicity risk assessment: Toward a possible harmonization of antigenicity assays
Published in mAbs, 2022
Axel Ducret, Chloé Ackaert, Juliana Bessa, Campbell Bunce, Timothy Hickling, Vibha Jawa, Mark A. Kroenke, Kasper Lamberth, Anaïs Manin, Hweixian L. Penny, Noel Smith, Grzegorz Terszowski, Sophie Tourdot, Sebastian Spindeldreher
Mechanistic modeling is used across drug development to support our understanding of complex systems and to provide simulations in predicting outcomes in experiments and in clinical trials. The integration of data from assays that investigate key mechanisms of the immune response in mathematical models is expected to result in better prediction of immunogenicity outcomes in clinical trials.87 Data that can be used for such modeling may be obtained from DC activation, protein uptake by DCs, T cell epitopes (in silico predicted and/or identified using MAPPs), and T cell proliferation assays. Model sensitivity analysis identifies inputs on DC activation, number of naïve T cells, and the affinity of HLA-peptide interactions as being most influential for ADA incidence simulations, indicating the high value of generating these data. Additional variables that are currently investigated (but which will require additional assays to refine modeling outputs) include B cell activation, B cell epitopes determination, B cell proliferation, and rate of ADA production. Also, extrinsic variables derived from ADA determination and PK/PD assays or from patient-centric parameters, such as individualized T and B cell epitopes and HLA genotyping, may also be included in modeling.