-
Journal of Pharmaceutical Sciences May 2016The success of clinical and commercial therapeutic proteins is rapidly increasing, but their potential immunogenicity is an ongoing concern. Most of the studies that... (Review)
Review
The success of clinical and commercial therapeutic proteins is rapidly increasing, but their potential immunogenicity is an ongoing concern. Most of the studies that have been conducted over the past few years to examine the importance of various product-related attributes (in particular several types of aggregates and particles) and treatment regimen (such as dose, dosing schedule, and route of administration) in the development of unwanted immune responses have utilized one of a variety of mouse models. In this review, we discuss the utility and drawbacks of different mouse models that have been used for this purpose. Moreover, we summarize the lessons these models have taught us and some of the challenges they present. Finally, we provide recommendations for future research utilizing mouse models to improve our understanding of critical factors that may contribute to protein immunogenicity.
Topics: Animals; Antibody Formation; Humans; Immunogenetic Phenomena; Immunoglobulin G; Immunoproteins; Mice; Mice, Transgenic; Models, Animal; Protein Aggregates; Species Specificity
PubMed: 27044944
DOI: 10.1016/j.xphs.2016.02.031 -
Current Opinion in Immunology Feb 2018Natural IgM are crucial for early protection against infection and play an important homeostatic function by clearing dead cells. The production of IgM is ensured by a... (Review)
Review
Natural IgM are crucial for early protection against infection and play an important homeostatic function by clearing dead cells. The production of IgM is ensured by a population of B cells with innate-like properties: their response is rapidly activated by innate signals early during the onset of infection. The main reservoir of innate-like B cells (IBCs) are the serous cavities, but their maintenance and activation depends on their relocation to a variety of lymphoid tissues. Recent advances indicate that fat-associated lymphoid clusters (FALCs) and milky spots contribute to local IgM secretion and play a central role in the localisation and regulation of IBC function.
Topics: Animals; Antibody Formation; B-Lymphocyte Subsets; Humans; Immunity, Innate; Immunoglobulin M; Lymphocyte Activation
PubMed: 29078198
DOI: 10.1016/j.coi.2017.10.006 -
Immunological Reviews Jul 2020Therapeutic vaccination offers great promise as an intervention for a diversity of infectious and non-infectious conditions. Given that most chronic health conditions... (Review)
Review
Therapeutic vaccination offers great promise as an intervention for a diversity of infectious and non-infectious conditions. Given that most chronic health conditions are thought to have an immune component, vaccination can at least in principle be proposed as a therapeutic strategy. Understanding the nature of protective immunity is of vital importance, and the progress made in recent years in defining the nature of pathological and protective immunity for a range of diseases has provided an impetus to devise strategies to promote such responses in a targeted manner. However, in many cases, limited progress has been made in clinical adoption of such approaches. This in part results from a lack of safe and effective vaccine adjuvants that can be used to promote protective immunity and/or reduce deleterious immune responses. Although somewhat simplistic, it is possible to divide therapeutic vaccine approaches into those targeting conditions where antibody responses can mediate protection and those where the principal focus is the promotion of effector and memory cellular immunity or the reduction of damaging cellular immune responses as in the case of autoimmune diseases. Clearly, in all cases of antigen-specific immunotherapy, the identification of protective antigens is a vital first step. There are many challenges to developing therapeutic vaccines beyond those associated with prophylactic diseases including the ongoing immune responses in patients, patient heterogeneity, and diversity in the type and stage of disease. If reproducible biomarkers can be defined, these could allow earlier diagnosis and intervention and likely increase therapeutic vaccine efficacy. Current immunomodulatory approaches related to adoptive cell transfers or passive antibody therapy are showing great promise, but these are outside the scope of this review which will focus on the potential for adjuvanted therapeutic active vaccination strategies.
Topics: Adjuvants, Immunologic; Animals; Antibody Formation; Autoimmunity; Disease Management; Humans; Immunity, Cellular; Immunity, Humoral; Immunomodulation; Molecular Targeted Therapy; Treatment Outcome; Vaccination; Vaccines
PubMed: 32594569
DOI: 10.1111/imr.12889 -
Signal Transduction and Targeted Therapy Jan 2023
Topics: Antibody Formation
PubMed: 36611028
DOI: 10.1038/s41392-022-01305-3 -
Journal of the Formosan Medical... May 2023
Topics: Humans; Antibody Formation; COVID-19; Vaccination; Drug-Related Side Effects and Adverse Reactions; Iatrogenic Disease; Vaccines, DNA; Antibodies, Viral
PubMed: 36610888
DOI: 10.1016/j.jfma.2022.12.018 -
Vaccine May 2022The animal-human interface has played a central role in advances made in vaccinology for the past two centuries. Many traditional veterinary vaccines were developed by... (Review)
Review
The animal-human interface has played a central role in advances made in vaccinology for the past two centuries. Many traditional veterinary vaccines were developed by growing, attenuating, inactivating and fractioning the pathogen of interest. While such approaches have been very successful, we have reached a point where they have largely been exhausted and alternative approaches are required. Furthermore, although subunit vaccines have enhanced safety profiles and created opportunities for combined discrimination between vaccinated and infected animal (DIVA) approaches, their functionality has largely been limited to diseases that can be controlled by humoral immunity until very recently. We now have a new generation of adjuvants and delivery systems that can elicit CD4 + T cells and/or CD8 + T cell responses in addition to high-titre antibody responses. We review the current vaccine platform technologies, describe their roles in veterinary vaccinology and discuss how knowledge of their mode of action allows informed decisions on their deployment with wider benefits for One Health.
Topics: Adjuvants, Immunologic; Animals; Antibody Formation; One Health; Vaccines, Subunit; Vaccinology
PubMed: 35382957
DOI: 10.1016/j.vaccine.2022.03.059 -
The Journal of Experimental Medicine Mar 2021The identification of discrete subclasses within the immunoglobulin G (IgG) isotype by Grey and Kunkel (1964. J. Exp. Med.https://doi.org/10.1084/jem.120.2.253) provided...
The identification of discrete subclasses within the immunoglobulin G (IgG) isotype by Grey and Kunkel (1964. J. Exp. Med.https://doi.org/10.1084/jem.120.2.253) provided the framework for our current understanding of differential IgG subclass activity in protective and self-reactive immune responses.
Topics: Antibody Formation; B-Lymphocytes; COVID-19; Glycosylation; Humans; Immunoglobulin G; Multiple Myeloma
PubMed: 33600555
DOI: 10.1084/jem.20201753 -
Frontiers in Immunology 2020The molecular machinery controlling immune development has been extensively investigated. Studies in animal models and adult individuals have revealed fundamental... (Review)
Review
The molecular machinery controlling immune development has been extensively investigated. Studies in animal models and adult individuals have revealed fundamental mechanisms of disease and have been essential to understanding how humans sense and respond to cellular stress, tissue damage, pathogens and their environment. Nonetheless, our understanding of how immune responses originate during human development is just starting to emerge. In particular, studies to unveil how environmental and other non-heritable factors shape the immune system at the beginning of life offer great promise to yield important knowledge about determinants of normal inter-individual immune variation and to prevent and treat many human diseases. In this review, we summarize our current understanding of some of the mechanisms determining early life antibody production as a model of an immune process with sequential molecular checkpoints susceptible to influence by non-heritable factors. We discuss the potential of epigenomics as a valuable approach that may reveal not only relevant gene-environment interactions but important clues about immune developmental processes and homeostasis in early life. We then highlight the novel paradigm of human immunology as a complex field that nowadays requires a longitudinal systems-biology approach to understand normal variation and developmental changes during the first few years of life.
Topics: Age Factors; Animals; Antibody Formation; Child Development; Epigenesis, Genetic; Epigenome; Gene Expression Regulation, Developmental; Gene-Environment Interaction; Humans; Immune System; Immunity, Humoral; Infant; Infant, Newborn
PubMed: 32983086
DOI: 10.3389/fimmu.2020.01766 -
Infection Apr 2023
Topics: Humans; BNT162 Vaccine; Antibody Formation; COVID-19 Vaccines; COVID-19; Antibodies, Viral
PubMed: 35925506
DOI: 10.1007/s15010-022-01898-5 -
Frontiers in Immunology 2018Antigens in particulate form have distinct immunologic properties relative to soluble antigens. An understanding of the mechanisms and functional consequences of the... (Review)
Review
Antigens in particulate form have distinct immunologic properties relative to soluble antigens. An understanding of the mechanisms and functional consequences of the distinct immunologic pathways engaged by these different forms of antigen is particularly relevant to the design of vaccines. It is also relevant regarding the use of therapeutic human proteins in clinical medicine that have been shown to aggregate, and perhaps as a result, elicit autoantibodies.
Topics: Animals; Antibody Formation; Antibody Specificity; Antigen-Presenting Cells; Antigens; B-Lymphocytes; Epitopes; Humans; Immune Tolerance; Immunity; Immunogenicity, Vaccine; Solubility; Vaccines
PubMed: 29619034
DOI: 10.3389/fimmu.2018.00598