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Vaccine Jun 2023Within-host models describe the dynamics of immune cells when encountering a pathogen, and how these dynamics can lead to an individual-specific immune response. This... (Review)
Review
BACKGROUND
Within-host models describe the dynamics of immune cells when encountering a pathogen, and how these dynamics can lead to an individual-specific immune response. This systematic review aims to summarize which within-host methodology has been used to study and quantify antibody kinetics after infection or vaccination. In particular, we focus on data-driven and theory-driven mechanistic models.
MATERIALS
PubMed and Web of Science databases were used to identify eligible papers published until May 2022. Eligible publications included those studying mathematical models that measure antibody kinetics as the primary outcome (ranging from phenomenological to mechanistic models).
RESULTS
We identified 78 eligible publications, of which 8 relied on an Ordinary Differential Equations (ODEs)-based modelling approach to describe antibody kinetics after vaccination, and 12 studies used such models in the context of humoral immunity induced by natural infection. Mechanistic modeling studies were summarized in terms of type of study, sample size, measurements collected, antibody half-life, compartments and parameters included, inferential or analytical method, and model selection.
CONCLUSIONS
Despite the importance of investigating antibody kinetics and underlying mechanisms of (waning of) the humoral immunity, few publications explicitly account for this in a mathematical model. In particular, most research focuses on phenomenological rather than mechanistic models. The limited information on the age groups or other risk factors that might impact antibody kinetics, as well as a lack of experimental or observational data remain important concerns regarding the interpretation of mathematical modeling results. We reviewed the similarities between the kinetics following vaccination and infection, emphasising that it may be worth translating some features from one setting to another. However, we also stress that some biological mechanisms need to be distinguished. We found that data-driven mechanistic models tend to be more simplistic, and theory-driven approaches lack representative data to validate model results.
Topics: Antibody Formation; Vaccination; Immunity, Humoral; Models, Theoretical
PubMed: 37198016
DOI: 10.1016/j.vaccine.2023.04.030 -
Current Opinion in Immunology Oct 2021Stringent regulation of IgE antibody production is critical for constraining allergic responses. This review discusses recent advances in understanding cell-intrinsic... (Review)
Review
Stringent regulation of IgE antibody production is critical for constraining allergic responses. This review discusses recent advances in understanding cell-intrinsic and extrinsic mechanisms that regulate the genesis and fate of IgE B cells. B cell-intrinsic regulation of IgE is orchestrated by the IgE B Cell Receptor (BCR). Through its antigen-independent signaling and low surface expression, the IgE BCR drives IgE B cells to differentiate into short-lived plasma cells and/or undergo apoptosis, restricting IgE-expressing cells from entering long-lived compartments. The pivotal extrinsic regulators of IgE responses are T follicular helper cells (T). T produce IL-4 and IL-21, which, respectively, are the major activating and inhibitory cytokines for IgE class-switching. Other newly identified T follicular subsets also contribute to IgE regulation. Although IgE responses are normally constrained, recent studies suggest that specific conditions can induce the formation of IgE responses with enhanced affinity or longevity, effectively 'breaking the rules' of IgE regulation.
Topics: Animals; Antibody Formation; Apoptosis; B-Lymphocytes; Cytokines; Disease Susceptibility; Gene Expression Regulation; Germinal Center; Humans; Hypersensitivity; Immunoglobulin E; Immunologic Memory; Immunomodulation; Plasma Cells; Receptors, Antigen, B-Cell
PubMed: 34216934
DOI: 10.1016/j.coi.2021.06.005 -
Cellular Immunology Dec 2022Protein based therapeutics have successfully improved the quality of life for patients of monogenic disorders like hemophilia, Pompe and Fabry disease. However, a... (Review)
Review
Protein based therapeutics have successfully improved the quality of life for patients of monogenic disorders like hemophilia, Pompe and Fabry disease. However, a significant proportion of patients develop immune responses towards intravenously infused therapeutic protein, which can complicate or neutralize treatment and compromise patient safety. Strategies aimed at circumventing immune responses following therapeutic protein infusion can greatly improve therapeutic efficacy. In recent years, antigen-based oral tolerance induction has shown promising results in the prevention and treatment of autoimmune diseases, food allergies and can prevent anti-drug antibody formation to protein replacement therapies. Oral tolerance exploits regulatory mechanisms that are initiated in the gut associated lymphoid tissue (GALT) to promote active suppression of orally ingested antigen. In this review, we outline general perceptions and current knowledge about the mechanisms of oral tolerance, including tissue specific sites of tolerance induction and the cells involved, with emphasis on antigen presenting cells and regulatory T cells. We define several factors, such as cytokines and metabolites that impact the stability and expansion potential of these immune modulatory cells. We highlight preclinical studies that have been performed to induce oral tolerance to therapeutic proteins or enzymes for single gene disorders, such as hemophilia or Pompe disease. These studies mainly utilize a transgenic plant-based system for oral delivery of antigen in conjugation with fusion protein technology that favors the prevention of antigen degradation in the stomach while enhancing uptake in the small intestine by antigen presenting cells and regulatory T cell induction, thereby promoting antigen specific systemic tolerance.
Topics: Humans; Hemophilia A; Antibody Formation; Quality of Life; Enzyme Replacement Therapy; Antibodies
PubMed: 36402002
DOI: 10.1016/j.cellimm.2022.104641 -
Frontiers in Immunology 2019Kawasaki disease (KD) is an inflammatory disease in children associated with vasculitis affecting predominantly the coronary arteries and is now the most common cause of... (Review)
Review
Kawasaki disease (KD) is an inflammatory disease in children associated with vasculitis affecting predominantly the coronary arteries and is now the most common cause of acquired heart disease in children in developed countries. The etiology of KD is unknown but epidemiological studies implicate an infectious agent or toxin, which causes disease in genetically predisposed individuals. The presence of immune complexes (ICs) in the serum of children with KD was established in numerous studies during the 1970s and 80s. More recent genetic studies have identified variation in Fcγ receptors and genes controlling immunoglobulin production associated with KD. In this review we link the genetic findings and IC studies and suggest a key role for their interaction in pathophysiology of the disease.
Topics: Antibody Formation; Antigen-Antibody Complex; Child; Coronary Vessels; Genetic Predisposition to Disease; Humans; Mucocutaneous Lymph Node Syndrome; Polymorphism, Genetic; Receptors, IgG
PubMed: 31263461
DOI: 10.3389/fimmu.2019.01156 -
Parasitology Feb 2016Malaria is one of the most serious infectious diseases with most of the severe disease caused by Plasmodium falciparum (Pf). Naturally acquired immunity develops over... (Review)
Review
Malaria is one of the most serious infectious diseases with most of the severe disease caused by Plasmodium falciparum (Pf). Naturally acquired immunity develops over time after repeated infections and the development of antimalarial antibodies is thought to play a crucial role. Neonates and young infants are relatively protected from symptomatic malaria through mechanisms that are poorly understood. The prevailing paradigm is that maternal antimalarial antibodies transferred to the fetus in the last trimester of pregnancy protect the infant from early infections. These antimalarial antibodies wane by approximately 6 months of age leaving the infant vulnerable to malaria, however direct evidence supporting this epidemiologically based paradigm is lacking. As infants are the target population for future malaria vaccines, understanding how they begin to develop immunity to malaria and the gaps in their responses is key. This review summarizes the antimalarial antibody responses detected in infants and how they change over time. We focus primarily on Pf antibody responses and will briefly mention Plasmodium vivax responses in infants.
Topics: Antibodies, Protozoan; Antibody Formation; Female; Humans; Infant; Infant, Newborn; Malaria, Falciparum; Malaria, Vivax; Pregnancy
PubMed: 26743626
DOI: 10.1017/S0031182015001626 -
Annals of Internal Medicine Jan 2023The durability of the antibody response after SARS-CoV-2 infection and the role of antibodies in protection against reinfection are unclear. (Review)
Review
BACKGROUND
The durability of the antibody response after SARS-CoV-2 infection and the role of antibodies in protection against reinfection are unclear.
PURPOSE
To synthesize evidence on the SARS-CoV-2 antibody response and reinfection risk with a focus on gaps identified in our prior reports.
DATA SOURCES
MEDLINE (Ovid), EMBASE, CINAHL, World Health Organization Research Database, and reference lists from 16 December 2021 through 8 July 2022, with surveillance through 22 August 2022.
STUDY SELECTION
English-language, cohort studies evaluating IgG antibody duration at least 12 months after SARS-CoV-2 infection, the antibody response among immunocompromised adults, predictors of nonseroconversion, and reinfection risk.
DATA EXTRACTION
Two investigators sequentially extracted study data and rated quality.
DATA SYNTHESIS
Most adults had IgG antibodies after SARS-CoV-2 infection at time points greater than 12 months (low strength of evidence [SoE]). Although most immunocompromised adults develop antibodies, the overall proportion with antibodies is lower compared with immunocompetent adults (moderate SoE for organ transplant patients and low SoE for patients with cancer or HIV). Prior infection provided substantial, sustained protection against symptomatic reinfection with the Delta variant (high SoE) and reduced the risk for severe disease due to Omicron variants (moderate SoE). Prior infection was less protective against reinfection with Omicron overall (moderate SoE), but protection from earlier variants waned rapidly (low SoE).
LIMITATION
Single review for abstract screening and sequential review for study selection, data abstraction, and quality assessment.
CONCLUSION
Evidence for a sustained antibody response to SARS-CoV-2 infection is considerable for both Delta and Omicron variants. Prior infection protected against reinfection with both variants, but, for Omicron, protection was weaker and waned rapidly. This information may have limited clinical applicability as new variants emerge.
PRIMARY FUNDING SOURCE
Agency for Healthcare Research and Quality. (PROSPERO: CRD42020207098).
Topics: United States; Adult; Humans; Antibody Formation; COVID-19; Reinfection; SARS-CoV-2; Immunoglobulin G
PubMed: 36442059
DOI: 10.7326/M22-1745 -
Journal of the American Geriatrics... Aug 2021See related editorial by Ouslander et al and related articles by Mor et al, Rudolph et al, and Domi et al. in this issue.
See related editorial by Ouslander et al and related articles by Mor et al, Rudolph et al, and Domi et al. in this issue.
Topics: Aged, 80 and over; Antibody Formation; COVID-19; Comorbidity; Disease Progression; Geriatrics; Humans; Immunoglobulin G; Long-Term Care; Time Factors; West Virginia
PubMed: 33939840
DOI: 10.1111/jgs.17210 -
Cell Reports. Medicine Oct 2022Protein nanoparticle scaffolds are increasingly used in next-generation vaccine designs, and several have established records of clinical safety and efficacy. Yet the...
Protein nanoparticle scaffolds are increasingly used in next-generation vaccine designs, and several have established records of clinical safety and efficacy. Yet the rules for how immune responses specific to nanoparticle scaffolds affect the immunogenicity of displayed antigens have not been established. Here we define relationships between anti-scaffold and antigen-specific antibody responses elicited by protein nanoparticle immunogens. We report that dampening anti-scaffold responses by physical masking does not enhance antigen-specific antibody responses. In a series of immunogens that all use the same nanoparticle scaffold but display four different antigens, only HIV-1 envelope glycoprotein (Env) is subdominant to the scaffold. However, we also demonstrate that scaffold-specific antibody responses can competitively inhibit antigen-specific responses when the scaffold is provided in excess. Overall, our results suggest that anti-scaffold antibody responses are unlikely to suppress antigen-specific antibody responses for protein nanoparticle immunogens in which the antigen is immunodominant over the scaffold.
Topics: HIV Antibodies; Antibody Formation; HIV-1; Nanoparticles; Glycoproteins; Vaccines
PubMed: 36206752
DOI: 10.1016/j.xcrm.2022.100780 -
Expert Opinion on Biological Therapy Jun 2016Multiple sclerosis (MS) is the most common chronic inflammatory, demyelinating disease of the CNS and results in neurological disability. Existing immunomodulatory and... (Review)
Review
INTRODUCTION
Multiple sclerosis (MS) is the most common chronic inflammatory, demyelinating disease of the CNS and results in neurological disability. Existing immunomodulatory and immunosuppressive approaches lower the number of relapses but do not cure or reverse existing deficits nor improve long-term disability in MS patients.
AREAS COVERED
Monogenic antibodies were described as treatment options for MS, however the immunogenicity of mouse antibodies hampered the efficacy of potential therapeutics in humans. Availability of improved antibody production technologies resulted in a paradigm shift in MS treatment strategies. In this review, an overview of immunotherapies for MS that use conventional monoclonal antibodies reactive to immune system and their properties and mechanisms of action will be discussed, including recent advances in MS therapeutics and highlight natural autoantibodies (NAbs) that directly target CNS cells.
EXPERT OPINION
Recent challenges for MS therapy are the identification of relevant molecular and cellular targets, time frame of treatment, and antibody toxicity profiles to identify safe treatment options for MS patients. The application of monoclonal antibody therapies with better biological efficacy associated with minimum side effects possesses huge clinical potential. Advances in monoclonal antibody technologies that directly target cells of nervous system may promote the CNS regeneration field from bench to bedside.
Topics: Animals; Antibodies, Monoclonal; Antibody Formation; Humans; Immunosuppressive Agents; Immunotherapy; Multiple Sclerosis
PubMed: 26914737
DOI: 10.1517/14712598.2016.1158809 -
Cellular & Molecular Immunology May 2021A mounting body of evidence indicates that dietary fiber (DF) metabolites produced by commensal bacteria play essential roles in balancing the immune system. DF,... (Review)
Review
A mounting body of evidence indicates that dietary fiber (DF) metabolites produced by commensal bacteria play essential roles in balancing the immune system. DF, considered nonessential nutrients in the past, is now considered to be necessary to maintain adequate levels of immunity and suppress inflammatory and allergic responses. Short-chain fatty acids (SCFAs), such as acetate, propionate, and butyrate, are the major DF metabolites and mostly produced by specialized commensal bacteria that are capable of breaking down DF into simpler saccharides and further metabolizing the saccharides into SCFAs. SCFAs act on many cell types to regulate a number of important biological processes, including host metabolism, intestinal functions, and immunity system. This review specifically highlights the regulatory functions of DF and SCFAs in the immune system with a focus on major innate and adaptive lymphocytes. Current information regarding how SCFAs regulate innate lymphoid cells, T helper cells, cytotoxic T cells, and B cells and how these functions impact immunity, inflammation, and allergic responses are discussed.
Topics: Animals; Antibody Formation; Fatty Acids, Volatile; Gastrointestinal Microbiome; Humans; Lymphocytes; Receptors, G-Protein-Coupled
PubMed: 33850311
DOI: 10.1038/s41423-020-00625-0