Manipulation of Innate and Adaptive Immunity through Cancer Vaccines

Although cancer immunotherapy has shown significant promise in mediating efficacious responses, it remains encumbered by tumor heterogeneity, loss of tumor-specific antigen targets, and the regulatory milieu both regionally and systemically. Cross talk between the innate and adaptive immune response may be requisite to polarize sustained antigen specific immunity. Cancer vaccines can serve as an essential fulcrum in initiating innate immunity while molding and sustaining adaptive immunity. Although peptide vaccines have shown tepid responses in a therapeutic setting with poor correlates for immune activity, RNA vaccines activate innate immune responses and have shown promising effects in preclinical and clinical studies based on enhanced DC migration. While the mechanistic insights behind the interplay between innate and adaptive immunity may be unique to the immunotherapeutic being investigated, understanding this dynamic is important to coordinate the different arms of the immune response in a focused response against cancer antigens.

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Introduction to Clinical Immunology: Overview of the Immune Response, Autoimmune Conditions, and Immunosuppressive Therapeutics for Rheumatic Diseases

10.2310/im.1328 ◽

2016 ◽

Author(s):

Steven K. Lundy ◽

Alison Gizinski ◽

David A. Fox

Keyword(s):

Immune Response ◽

Immune System ◽

T Cell ◽

Immune Responses ◽

Autoimmune Diseases ◽

Adaptive Immunity ◽

Cell Populations ◽

Hematopoietic Stem ◽

Innate And Adaptive Immunity ◽

Adaptive Immune

The immune system is a complex network of cells and mediators that must balance the task of protecting the host from invasive threats. From a clinical perspective, many diseases and conditions have an obvious link to improper functioning of the immune system, and insufficient immune responses can lead to uncontrolled acute and chronic infections. The immune system may also be important in tumor surveillance and control, cardiovascular disease, health complications related to obesity, neuromuscular diseases, depression, and dementia. Thus, a working knowledge of the role of immunity in disease processes is becoming increasingly important in almost all aspects of clinical practice. This review provides an overview of the immune response and discusses immune cell populations and major branches of immunity, compartmentalization and specialized immune niches, antigen recognition in innate and adaptive immunity, immune tolerance toward self antigens, inflammation and innate immune responses, adaptive immune responses and helper T (Th) cell subsets, components of the immune response that are important targets of treatment in autoimmune diseases, mechanisms of action of biologics used to treat autoimmune diseases and their approved uses, and mechanisms of other drugs commonly used in the treatment of autoimmune diseases. Figures show the development of erythrocytes, platelets, lymphocytes, and other immune system cells originating from hematopoietic stem cells that first reside in the fetal liver and later migrate to the bone marrow, antigen–major histocompatibility complex recognition by T cell receptor control of T cell survival and activation, and Th cells as central determinants of the adaptive immune response toward different stimuli. Tables list cell populations involved in innate and adaptive immunity, pattern recognition receptors with known ligands, autoantibody-mediated human diseases: examples of pathogenic mechanisms, selected Food and Drug Administration–approved autoimmune disease indications for biologics, and mechanism of action of biologics used to treat autoimmune diseases. This review contains 3 highly rendered figures, 5 tables, and 64 references.

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Adaptive immunity

Oxford Textbook of Medicine ◽

10.1093/med/9780199204854.003.050103 ◽

2010 ◽

pp. 224-234

Author(s):

Paul Klenerman

Keyword(s):

Infectious Disease ◽

Immune Response ◽

Pattern Recognition ◽

Adaptive Immunity ◽

Adaptive Response ◽

Critical Role ◽

Adaptive Immune Response ◽

Structural Features ◽

Adaptive Immune ◽

Single Organism

Following the innate immune response, which acts very rapidly, the adaptive immune response plays a critical role in host defence against infectious disease. Unlike the innate response, which is triggered by pattern recognition of pathogens, i.e. features that are common to many bacteria or viruses, the adaptive response is triggered by structural features—known as antigens or epitopes—that are typically unique to a single organism....

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Adaptive immunity

Oxford Textbook of Medicine ◽

10.1093/med/9780198746690.003.0040 ◽

2020 ◽

pp. 325-336

Author(s):

Paul Klenerman

Keyword(s):

Immune Response ◽

Immune Responses ◽

Adaptive Immunity ◽

Innate Immune Response ◽

Molecular Basis ◽

Adaptive Immune Response ◽

Antigenic Specificity ◽

Adaptive Immune Responses ◽

Research Attention ◽

Adaptive Immune

The adaptive immune response is distinguished from the innate immune response by two main features: its capacity to respond flexibly to new, previously unencountered antigens (antigenic specificity), and its enhanced capacity to respond to previously encountered antigens (immunological memory). These two features have provided the focus for much research attention, from the time of Jenner, through Pasteur onwards. Historically, innate and adaptive immune responses have often been treated as separate, with the latter being considered more ‘advanced’ because of its flexibility. It is now clear this not the case, and in recent years the molecular basis for these phenomena has become much better understood.

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Adaptive Immune Response to Shigella flexneri 2acydC in Immunocompetent Mice and Mice Lacking Immunoglobulin A

Infection and Immunity ◽

10.1128/iai.67.4.2001-2004.1999 ◽

1999 ◽

Vol 67 (4) ◽

pp. 2001-2004 ◽

Cited By ~ 20

Author(s):

Sing Sing Way ◽

Alain C. Borczuk ◽

Marcia B. Goldberg

Keyword(s):

Immune Response ◽

Adaptive Immunity ◽

Shigella Flexneri ◽

Immunoglobulin A ◽

Adaptive Immune Response ◽

Model System ◽

Wild Type ◽

Adaptive Immune ◽

Immunocompetent Mice

ABSTRACT Shigella flexneri cydC, which is deficient in cytochrome bd, was rapidly cleared from the lungs of intranasally inoculated mice and was Sereny negative, yet it induced 93% protection against challenge with wild-type S. flexneri. Mice that lack immunoglobulin A (IgA) were fully protected, suggesting that IgA may not be required for adaptive immunity in this model system.

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Innate and Adaptive Immunity in Calcific Aortic Valve Disease

Journal of Immunology Research ◽

10.1155/2015/851945 ◽

2015 ◽

Vol 2015 ◽

pp. 1-11 ◽

Cited By ~ 39

Author(s):

Patrick Mathieu ◽

Rihab Bouchareb ◽

Marie-Chloé Boulanger

Keyword(s):

Immune Response ◽

Aortic Valve ◽

Adaptive Immunity ◽

Aortic Valve Disease ◽

Adaptive Immune Response ◽

Valve Disease ◽

Calcific Aortic Valve Disease ◽

Innate And Adaptive Immunity ◽

Ectopic Mineralization ◽

Lipid Species

Calcific aortic valve disease (CAVD) is the most common heart valve disorder. CAVD is a chronic process characterized by a pathologic mineralization of valve leaflets. Ectopic mineralization of the aortic valve involves complex relationships with immunity. Studies have highlighted that both innate and adaptive immunity play a role in the development of CAVD. In this regard, accumulating evidence indicates that fibrocalcific remodelling of the aortic valve is associated with activation of the NF-κB pathway. The expression of TNF-αand IL-6 is increased in human mineralized aortic valves and promotes an osteogenic program as well as the mineralization of valve interstitial cells (VICs), the main cellular component of the aortic valve. Different factors, including oxidized lipid species, activate the innate immune response through the Toll-like receptors. Moreover, VICs express 5-lipoxygenase and therefore produce leukotrienes, which may amplify the inflammatory response in the aortic valve. More recently, studies have emphasized that an adaptive immune response is triggered during CAVD. Herein, we are reviewing the link between the immune response and the development of CAVD and we have tried, whenever possible, to keep a translational approach.

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Human neutrophil elastase inhibitors in innate and adaptive immunity

Biochemical Society Transactions ◽

10.1042/bst0340279 ◽

2006 ◽

Vol 34 (2) ◽

pp. 279-282 ◽

Cited By ~ 29

Author(s):

P.M. Fitch ◽

A. Roghanian ◽

S.E.M. Howie ◽

J.-M. Sallenave

Keyword(s):

Neutrophil Elastase ◽

Human Neutrophil ◽

Adaptive Immune Response ◽

Antimicrobial Activities ◽

Innate Immune ◽

Human Neutrophil Elastase ◽

Innate Immune Responses ◽

Innate And Adaptive Immunity ◽

Adaptive Immune ◽

Pleiotropic Functions

Recent evidence shows that human neutrophil elastase inhibitors can be synthesized locally at mucosal sites. In addition to efficiently targeting bacterial and host enzymes, they can be released in the interstitium and in the lumen of mucosa, where they have been shown to have antimicrobial activities, and to activate innate immune responses. This review will address more particularly the pleiotropic functions of low-molecular-mass neutrophil elastase inhibitors [SLPI (secretory leucocyte proteinase inhibitor) and elafin] and, more specifically, their role in the development of the adaptive immune response.

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A Nanoscaffolded Spike-RBD Vaccine Provides Protection against SARS-CoV-2 with Minimal Anti-Scaffold Response

Vaccines ◽

10.3390/vaccines9050431 ◽

2021 ◽

Vol 9 (5) ◽

pp. 431

Author(s):

Duško Lainšček ◽

Tina Fink ◽

Vida Forstnerič ◽

Iva Hafner-Bratkovič ◽

Sara Orehek ◽

...

Keyword(s):

Immune Response ◽

Neutralizing Antibodies ◽

Specific Antigen ◽

Adaptive Immune Response ◽

Adaptive Immune System ◽

T Cell Response ◽

Viral Neutralization ◽

Adaptive Immune ◽

Lumazine Synthase ◽

Antibody Titers

The response of the adaptive immune system is augmented by multimeric presentation of a specific antigen, resembling viral particles. Several vaccines have been designed based on natural or designed protein scaffolds, which exhibited a potent adaptive immune response to antigens; however, antibodies are also generated against the scaffold, which may impair subsequent vaccination. In order to compare polypeptide scaffolds of different size and oligomerization state with respect to their efficiency, including anti-scaffold immunity, we compared several strategies of presentation of the RBD domain of the SARS-CoV-2 spike protein, an antigen aiming to generate neutralizing antibodies. A comparison of several genetic fusions of RBD to different nanoscaffolding domains (foldon, ferritin, lumazine synthase, and β-annulus peptide) delivered as DNA plasmids demonstrated a strongly augmented immune response, with high titers of neutralizing antibodies and a robust T-cell response in mice. Antibody titers and virus neutralization were most potently enhanced by fusion to the small β-annulus peptide scaffold, which itself triggered a minimal response in contrast to larger scaffolds. The β-annulus fused RBD protein increased residence in lymph nodes and triggered the most potent viral neutralization in immunization by a recombinant protein. Results of the study support the use of a nanoscaffolding platform using the β-annulus peptide for vaccine design.

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The Gut Microbiota Is Associated with Clearance ofClostridium difficileInfection Independent of Adaptive Immunity

mSphere ◽

10.1128/mspheredirect.00698-18 ◽

2019 ◽

Vol 4 (1) ◽

Cited By ~ 11

Author(s):

Jhansi L. Leslie ◽

Kimberly C. Vendrov ◽

Matthew L. Jenior ◽

Vincent B. Young

Keyword(s):

United States ◽

Immune Response ◽

Clostridium Difficile ◽

Gut Microbiota ◽

Adaptive Immunity ◽

Adaptive Immune Response ◽

The United States ◽

Content Type ◽

Adaptive Immune

ABSTRACTClostridium(Clostridioides)difficile, a Gram-positive, anaerobic bacterium, is the leading single cause of nosocomial infections in the United States. A major risk factor forClostridium difficileinfection (CDI) is prior exposure to antibiotics, as they increase susceptibility to CDI by altering the membership of the microbial community enabling colonization. The importance of the gut microbiota in providing protection from CDI is underscored by the reported 80 to 90% success rate of fecal microbial transplants in treating recurrent infections. Adaptive immunity, specifically humoral immunity, is also sufficient to protect from both acute and recurrent CDI. However, the role of the adaptive immune system in mediating clearance ofC. difficilehas yet to be resolved. Using murine models of CDI, we found that adaptive immunity is dispensable for clearance ofC. difficile. However, random forest analysis using only two members of the resident bacterial community correctly identified animals that would go on to clear the infection with 66.7% accuracy. These findings indicate that the indigenous gut microbiota independent of adaptive immunity facilitates clearance ofC. difficilefrom the murine gastrointestinal tract.IMPORTANCEClostridium difficileinfection is a major cause of morbidity and mortality in hospitalized patients in the United States. Currently, the role of the adaptive immune response in modulating levels ofC. difficilecolonization is unresolved. This work suggests that the indigenous gut microbiota is a main factor that promotes clearance ofC. difficilefrom the GI tract. Our results show that clearance ofC. difficilecan occur without contributions from the adaptive immune response. This study also has implications for the design of preclinical studies testing the efficacy of vaccines on clearance of bacterial pathogens, as inherent differences in the baseline community structure of animals may bias findings.

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The gut microbiota is associated with clearance of Clostridium difficile infection independent of adaptive immunity

10.1101/512616 ◽

2019 ◽

Author(s):

Jhansi L. Leslie ◽

Kimberly C. Vendrov ◽

Matthew L. Jenior ◽

Vincent B. Young

Keyword(s):

United States ◽

Immune Response ◽

Gut Microbiota ◽

Adaptive Immunity ◽

Adaptive Immune Response ◽

Recurrent Infection ◽

Adaptive Immune System ◽

The United States ◽

Adaptive Immune

AbstractClostridium (Clostridioides) difficile, a Gram-positive, anaerobic bacterium is the leading single cause of nosocomial infections in the United States. A major risk factor for C. difficile infection (CDI) is prior exposure to antibiotics as they increase susceptibility to CDI by altering the membership of the microbial community enabling colonization. The importance of the gut microbiota in providing protection from CDI is underscored by the reported 80-90% success rate of fecal microbial transplants in treating recurrent infection. Adaptive immunity, specifically humoral immunity, is also sufficient to protect from both acute and recurrent CDI. However, the role of the adaptive immune system in mediating clearance of C. difficile has yet to be resolved. Using murine models of CDI, we found that adaptive immunity is dispensable for clearance of C. difficile. However, Random Forest analysis using only 2 members of the resident bacterial community correctly identified animals that would go on to clear the infection with 66.7% accuracy. These findings indicate that the indigenous gut microbiota independent of adaptive immunity facilitates clearance of C. difficile from the murine gastrointestinal tract.ImportanceC. difficile infection is a major cause of morbidity and mortality in hospitalized patients in the United States. Currently the role of the adaptive immune response in modulating levels of C. difficile colonization is unresolved. This work suggests that the indigenous gut microbiota is a main factor that promotes clearance of C. difficile from the GI tract. Our results show that clearance of C. difficile can occur without contributions from the adaptive immune response. This study also has implications for the design of preclinical studies testing the efficacy of vaccines on clearance of bacterial pathogens as inherent differences in the baseline community structure of animals may bias findings.

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Prophylactic Cancer Vaccines Engineered to Elicit Specific Adaptive Immune Response

Frontiers in Oncology ◽

10.3389/fonc.2021.626463 ◽

2021 ◽

Vol 11 ◽

Author(s):

Davis W. Crews ◽

Jenna A. Dombroski ◽

Michael R. King

Keyword(s):

Immune Response ◽

Cancer Vaccines ◽

Tumor Development ◽

Adaptive Immune Response ◽

The United States ◽

Adaptive Responses ◽

Adaptive Immune ◽

B Virus ◽

Different Types ◽

Antigen Presenting

Vaccines have been used to prevent and eradicate different diseases for over 200 years, and new vaccine technologies have the potential to prevent many common illnesses. Cancer, despite many advances in therapeutics, is still the second leading causes of death in the United States. Prophylactic, or preventative, cancer vaccines have the potential to reduce cancer prevalence by initiating a specific immune response that will target cancer before it can develop. Cancer vaccines can include many different components, such as peptides and carbohydrates, and be fabricated for delivery using a variety of means including through incorporation of stabilizing chemicals like polyethylene glycol (PEG) and pan-DR helper T-lymphocyte epitope (PADRE), fusion with antigen-presenting cells (APCs), microneedle patches, and liposomal encapsulation. There are currently five cancer vaccines used in the clinic, protecting against either human papillomavirus (HPV) or hepatitis B virus (HBV), and preventing several different types of cancer including cervical and oral cancer. Prophylactic cancer vaccines can promote three different types of adaptive responses: humoral (B cell, or antibody-mediated), cellular (T cell) or a combination of the two types. Each vaccine has its advantages and challenges at eliciting an adaptive immune response, but these prophylactic cancer vaccines in development have the potential to prevent or delay tumor development, and reduce the incidence of many common cancers.

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