Adaptive immune response: Antigens, lymphocytes, and accessory cells
Gabriel Virella in Medical Immunology, 2019
Antigenicity is defined as the property of a substance (antigen) that allows it to react with the products of a specific immune response (antibody or T-cell receptor). Immunogenicity is defined as the property of a substance (immunogen) that endows it with the capacity to provoke a specific immune response. From these definitions, it follows that all immunogens are antigens; the reverse, however, is not true, as discussed later. B-cell immunogens are usually complex, large molecules, able to interact with B-cell surface receptors (membrane immunoglobulins) and deliver by themselves the initial activating signal leading to clonal expansion and differentiation of antibody-producing cells. T-cell immunogens can be best defined as compounds that can be processed by antigen-presenting cells into short polypeptide chains that combine with major histocompatibility complex (MHC) molecules; the peptide-MHC complexes are able to interact with specific T-cell receptors and deliver activating signals to the T cells carrying such receptors. Landsteiner, Pauling, and others discovered in the 1930s and 1940s that small aromatic groups, such as amino-benzene sulfonate, amino-benzene arsenate, and amino-benzene carboxylate, unable to induce antibody responses by themselves, could be chemically coupled to immunogenic proteins. The injection of these complexes into laboratory animals resulted in the production of antibodies specific for the different aromatic groups. The aromatic groups were designated as “haptens” and the immunogenic proteins as “carriers.”The immune response induced by a hapten-carrier conjugate included antibodies able to recognize the hapten and the carrier as separate entities. The hapten-specific antibodies are also able to react with soluble hapten molecules, free of carrier protein. Thus, a hapten is an antigen but not an immunogen. In practical terms, it must be noted that the designations of antigen and immunogen are often used interchangeably.
Clinical Trials
Abhaya Indrayan in Research Methods for Medical Graduates, 2019
The intervention in this case is a potential vaccine to prevent the occurrence or progression of a disease. Vaccine trials are conducted in phases just as therapeutic trials are done but need even more precaution. The need for extra care arises from the applicability of vaccines to a large segment of the populations who are not sick but are at risk, as opposed to therapeutics that is applied only to patients and administered under close supervision. A feature of vaccines is immunogenicity, which might be an important consideration in some diseases, in addition to protective efficacy. In some others, duration of protection may be important. The quality and quantity of immune responses required for protection against infection and against development of disease are scientific challenges. In the case of HIV, for example, there could be a vaccine that inhibits HIV infection, and there could be a vaccine that inhibits or retards the development of disease – AIDS – in those already infected. In view of the complexities involved in vaccine trials, an additional phase called phase IIB (see phases of a clinical trial later in this chapter) is sometimes advocated. This is also called the “test of concept” phase. The aim of phase IIA could be to establish the schedule of administration for different age groups as it would be most likely a factorial experiment with dose level as one factor and age group as the second factor. Thus, four phases are required for vaccine trials instead of the usual three. The objective of phase IIB is to evaluate whether the vaccine has any (>0%) efficacy at all. In a phase III trial for vaccines, this objective shifts generally to at least 30% efficacy. The participants in phase IIB are not necessarily representative of the target population.
Neurological events following immunizations
Avindra Nath, Joseph R. Berger in Clinical Neurovirology, 2020
Nucleic acid-based vaccines entail the use of DNA which encodes a vaccine antigen. The in vitro model for this approach involves the transformation of cells in culture with a plasmid that directs the synthesis of a vaccine antigen. After cells in vivo take up DNA encoding the vaccine antigens, the antigens can be secreted or incorporated into the cell surface and produce a humoral or cellular immune response. The initial strategy for this has been to inject intramuscularly a solution of uncoated (“naked”) DNA encoding a vaccine antigen; cells then take up the DNA, transcribe and synthesize the antigen, and process it similarly to a live viral infection, producing a humoral or cellular immune response to the encoded antigen [10]. Facilitation of DNA incorporation may be achieved at several different levels in the process. Alternatively, plasmid expression may be achieved by incorporating a vaccine-antigen plasmid into a nonpathogenic viral “vector.”During infection with the nonpathogenic vector, protein from the DNA of the virulent microorganism is also presented to the immune system without infection by the virulent organism [11]. This technique has been explored in the development of vaccines for various flaviviruses, malaria, and other pathogens [12–15]. More recently, DNA vaccines have been explored as a potential immunotherapy for various cancers [16,17]. 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. Vaccines may be used for varying purposes. Many vaccines are widely used and are given in childhood to prevent various childhood infections (e.g., measles, mumps, rubella) [19,20]. Vaccine schedules for the United States can be found on the U.S. Centers for Disease Control and Prevention (CDC) website at: https://www.cdc.gov/vaccines/schedules/hcp/imz/child-adolescent.html [19]. Some vaccines are given predominantly in the setting of a suspected exposure to a particular infectious agent (e.g., rabies vaccine in the setting of suspected exposure to a rabid animal) [21]. Some vaccines are used in specific settings, such as in attempts to control an outbreak of disease; this is true, for instance, with typhoid, meningococcal, and cholera vaccines [22,23].
Methods for predicting vaccine immunogenicity and reactogenicity
Published in Human Vaccines & Immunotherapeutics, 2020
Patrícia Gonzalez-Dias, Eva K. Lee, Sara Sorgi, Diógenes S. de Lima, Alysson H. Urbanski, Eduardo Lv Silveira, Helder I. Nakaya
Subjects receiving the same vaccine often show different levels of immune responses and some may even present adverse side effects to the vaccine. Systems vaccinology can combine omics data and machine learning techniques to obtain highly predictive signatures of vaccine immunogenicity and reactogenicity. Currently, several machine learning methods are already available to researchers with no background in bioinformatics. Here we described the four main steps to discover markers of vaccine immunogenicity and reactogenicity: (1) Preparing the data; (2) Selecting the vaccinees and relevant genes; (3) Choosing the algorithm; (4) Blind testing your model. With the increasing number of Systems Vaccinology datasets being generated, we expect that the accuracy and robustness of signatures of vaccine reactogenicity and immunogenicity will significantly improve.
An update on safety and immunogenicity of vaccines containing emulsion-based adjuvants
Published in Expert Review of Vaccines, 2013
Christopher B Fox, Jean Haensler
With the exception of alum, emulsion-based vaccine adjuvants have been administered to far more people than any other adjuvant, especially since the 2009 H1N1 influenza pandemic. The number of clinical safety and immunogenicity evaluations of vaccines containing emulsion adjuvants has correspondingly mushroomed. In this review, the authors introduce emulsion adjuvant composition and history before detailing the most recent findings from clinical and postmarketing data regarding the effects of emulsion adjuvants on vaccine immunogenicity and safety, with emphasis on the most widely distributed emulsion adjuvants, MF59® and AS03. The authors also present a summary of other emulsion adjuvants in clinical development and indicate promising avenues for future emulsion-based adjuvant development. Overall, emulsion adjuvants have demonstrated potent adjuvant activity across a number of disease indications along with acceptable safety profiles.
Molecular mechanisms for enhanced DNA vaccine immunogenicity
Published in Expert Review of Vaccines, 2016
In the two decades since their initial discovery, DNA vaccines technologies have come a long way. Unfortunately, when applied to human subjects inadequate immunogenicity is still the biggest challenge for practical DNA vaccine use. Many different strategies have been tested in preclinical models to address this problem, including novel plasmid vectors and codon optimization to enhance antigen expression, new gene transfection systems or electroporation to increase delivery efficiency, protein or live virus vector boosting regimens to maximise immune stimulation, and formulation of DNA vaccines with traditional or molecular adjuvants. Better understanding of the mechanisms of action of DNA vaccines has also enabled better use of the intrinsic host response to DNA to improve vaccine immunogenicity. This review summarizes recent advances in DNA vaccine technologies and related intracellular events and how these might impact on future directions of DNA vaccine development.
Related Knowledge Centers
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