Teaching vaccine development in schools: Learnings from a survey and curriculum design for a course

Although vaccines are being developed and administered to people for more than a century, the understanding of the steps involved in vaccine development is a relatively new subject to the general public. During the current pandemic, there has been an explosion of non-validated news about COVID-19 and vaccines. To enhance the understanding of this critical societal science, there is an urgent need to teach these topics in the early education systems. Defining the essential subjects and courses for high school and developing syllabi for undergraduate courses in immunology and vaccinology can be difficult, as students choose diverse career options after their studies. To define these curricula, understanding the current level of awareness regarding vaccinology and immunology among students becomes essential. Thus, we have undertaken an exploratory survey of 650 high school and undergraduate college students in India on their awareness of the processes of vaccine development. Our results confirmed our hypothesis that there is a very limited understanding of this topic among school-going students. In this article, we propose an outline for a course for teaching in high schools. We recommend that this course should be interdisciplinary and a mix and match of majors and minors. It should train students with soft skills and prepare them for their careers in biomedical research

Assessment of immunogenicity of romiplostim in clinical studies with ITP subjects

Romiplostim is an Fc-peptide fusion protein that activates intracellular transcriptional pathways via the thrombopoietin (TPO) receptor leading to increased platelet production. Romiplostim has been engineered to have no amino acid sequence homology to endogenous TPO. Recombinant protein therapeutics can be at a risk of development of an antibody response that can impact efficacy and safety. Hence, a strategy to detect potential antibody formation to the drug and to related endogenous molecules can be useful. The immunogenicity assessment strategy involved both the detection and characterization of binding and neutralizing antibodies. The method for detection was based on a surface plasmon resonance biosensor platform using the Biacore 3000. Samples that tested positive for binding antibodies in the Biacore immunoassay were then tested in a neutralization assay. Serum samples from 225 subjects with immune thrombocytopenic purpura (ITP) dosed with romiplostim and 45 ITP subjects dosed with placebo were tested for romiplostim and TPO antibodies. Prior to romiplostim treatment, 17 subjects (7%) tested romiplostim antibody positive and 12 subjects (5%) tested TPO antibody positive for pre-existing binding antibodies. After romiplostim exposure, 11% of the subjects exhibited binding antibodies against romiplostim and 5% of the subjects with ITP showed binding antibodies against TPO. The antibodies against romiplostim did not cross-react with TPO and vice versa. No cases of anti-TPO neutralizing antibodies were detected in romiplostim-treated subjects. The incidence of anti-romiplostim neutralizing antibodies to romiplostim was 0.4% (one subject); this subject tested negative at the time of follow-up 4 months later. No impact on platelet profiles were apparent in subjects that had antibodies to romiplostim to date. In summary, administration of romiplostim in ITP subjects resulted in the development of a binding antibody response against romiplostim and TPO ligand. One subject developed a neutralizing antibody response to romiplostim that impacted the platelet counts of this subject. No neutralizing antibodies to endogenous TPO were observed

Influences of related retroviruses on lymphocyte functions

The human immunodeficiency virus (HIV‐1) is known to be profoundly immunosuppressive [Spickett and Dalgleish (1988) Clin. Exp. Immunol. 71, 1]. In this communication, we have studied the influences of HIV‐1 (BH10), HIV‐2 (LAV‐2) and STLV‐3 on B and T cells from healthy volunteers. B lymphocytes were found to differentiate into immunoglobulin secreting cells in response to stimulation by proteins of HIV‐1 and LAV‐2, but not by STLV‐3. This response was obtained at protein concentrations of 0.05‐0.005 μg/ml and was T cell dependent. IgM secretion was induced only by HIV‐1 in the EBV‐transformed B cell line SKW 6.4. At higher concentrations all three retroviral preparations had inhibitory influences on functions of B as well as T lymphocytes. B cell differentiation was maximally inhibited by HIV‐1 and LAV‐2 when these proteins were added concurrently to cultures with the polyclonal B cell activators pokeweed mitogen or Epstein‐Barr virus. Tetanus antigen‐specific T cell lymphoproliferation was inhibited by all retroviral proteins. These findings suggest that related retroviruses differ in their capacity to influence normal immune responses

Immunogenicity of Biotherapeutics: Causes and Association with Posttranslational Modifications

Today, potential immunogenicity can be better evaluated during the drug development process, and we have rational approaches to manage the clinical consequences of immunogenicity. The focus of the scientific community should be on developing sensitive diagnostics that can predict immunogenicity-mediated adverse events in the small fraction of subjects that develop clinically relevant anti-drug antibodies. Here, we discuss the causes of immunogenicity which could be product-related (inherent property of the product or might be picked up during the manufacturing process), patient-related (genetic profile or eating habits), or linked to the route of administration. We describe various posttranslational modifications (PTMs) and how they may influence immunogenicity. Over the last three decades, we have significantly improved our understanding about the types of PTMs of biotherapeutic proteins and their association with immunogenicity. It is also now clear that all PTMs do not lead to clinical immunogenicity. We also discuss the mechanisms of immunogenicity (which include T cell-dependent and T cell-independent responses) and immunological tolerance. We further elaborate on the management of immunogenicity in preclinical and clinical setting and the unique challenges raised by biosimilars, which may have different immunogenic potential from their parent biotherapeutics

Nef protein of HIV-1 has B-cell stimulatory activity

To examine the B-cell stimulatory properties of the regulatory Nef protein of HIV-1. The effect of the HIV-1 regulatory proteins Nef, Tat and Vif, were analyzed for their ability to induce differentiation of normal B lymphocytes into immunoglobulin secreting cells (ISC). A recombinant Nef protein, but neither Tat or Vif, was able to induce ISC in peripheral blood lymphocyte (PBL) cultures of HIV-1-seronegative donors. Another recombinant Nef protein, d-Nef, with a truncated amino terminal (deletion of 34 amino acids) failed to induce B-cell differentiation. Pretreatment of the Nef protein with a polyclonal anti-Nef-antibody abrogated its B-cell stimulatory activity. The Nef-induced B-cell differentiation was dependent on cell-to-cell contact. Cell surface molecules leukocyte function-associated molecule (LFA)-1, intracellular adhesion molecule (ICAM)-1, human lymphocyte antigen-DR and B7 were involved in the T-B-cell interaction because monoclonal antibodies to these molecules abrogated the Nef-induced B-cell differentiation response. The Nef protein was able to induce interleukin (IL)-6 messenger (m)RNA and IL-6 protein secretion in PBL, with monocytes as the primary source. These findings indicate that regulatory (Nef) proteins of HIV-1 contribute to the intense B-cell activation that occurs in association with HIV-1 infection. T-B-cell contact-dependent interaction and induction of IL-6 by these proteins appear to play major roles in this process