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Current Opinion in Immunology

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https://www.readbyqxmd.com/read/28806603/cancer-vaccines-in-the-era-of-checkpoint-blockade-the-magic-is-in-the-adjuvant
#1
REVIEW
Willem W Overwijk
While T cell checkpoint blockade therapy of various cancers yields impressive clinical benefits, most patients are not cured. This is thought to result from insufficient spontaneous tumor-specific T cell responses, a situation that could be remedied with cancer-specific vaccination. Much work is underway to identify cancer-specific antigens, leaving open the question of how to formulate these antigens in a manner that provokes potent cancer-specific T cell responses. In this review I discuss paradigms guiding adjuvant development, and consider what may constitutes a clinically relevant T cell response...
August 11, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28806575/lessons-from-ctla-4-deficiency-and-checkpoint-inhibition
#2
REVIEW
Bernice Lo, Ussama M Abdel-Motal
CTLA-4 is a crucial negative regulator of immune responses. Absence of CTLA-4 in mice causes autoimmunity and lethal multiorgan lymphocytic infiltration and tissue destruction. Recently, heterozygous CTLA4 or biallelic LRBA mutations leading to functional CTLA-4 deficiency and autoimmunity have been discovered. LRBA was identified as a novel regulator of steady-state CTLA-4 protein levels in Tregs and activated T cells. CTLA-4 deficiency due to checkpoint blockade cancer immunotherapy has also been found to lead to autoimmune reactions...
August 11, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28780492/known-unknowns-how-might-the-persistent-herpesvirome-shape-immunity-and-aging
#3
REVIEW
Janko Nikolich-Zugich, Felicia Goodrum, Kenneth Knox, Megan J Smithey
The microbial community that colonizes all living organisms is gaining appreciation for its contributions to both physiologic and pathogenic processes. The virome, a subset of the overall microbiome, large and diverse, including viruses that persistently inhabit host cells, endogenous viral elements genomically or epigenomically integrated into cells, and viruses that infect the other (bacterial, protozoan, fungal, and archaeal) microbiome phylla. These viruses live in the organism for its life, and therefore are to be considered part of the aging process experienced by the organism...
August 3, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28780294/pathophysiology-and-immunological-profile-of-myasthenia-gravis-and-its-subgroups
#4
REVIEW
Fredrik Romi, Yu Hong, Nils Erik Gilhus
Myasthenia gravis (MG) is an autoimmune antibody-mediated disease characterized by muscle weakness and fatigability. It is believed that the initial steps triggering humoral immunity in MG take place inside thymic tissue and thymoma. The immune response against one or several epitopes expressed on thymic tissue cells spills over to neuromuscular junction components sharing the same epitope causing humoral autoimmunity and antibody production. The main cause of MG is acetylcholine receptor antibodies. However, many other neuromuscular junction membrane protein targets, intracellular and extracellular proteins are suggested to participate in MG pathophysiology...
August 3, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28756233/organoid-culture-systems-to-study-host-pathogen-interactions
#5
REVIEW
Devanjali Dutta, Hans Clevers
Recent advances in host-microbe interaction studies in organoid cultures have shown great promise and have laid the foundation for much more refined future studies using these systems. Modeling of Zika virus (ZIKV) infection in cerebral organoids have helped us understand its association with microcephaly. Similarly, the pathogenesis of bacterial (Helicobacter pylori, Clostridium difficile) and viral (Norovirus, Rotaviruses) infections have been precisely dissected in organoid cultures. Additionally, direct associations between microbial colonization of tissues and diseases like cancer have also been deciphered...
July 27, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28755542/towards-an-evidence-based-approach-for-the-development-of-adjuvanted-vaccines
#6
REVIEW
Derek T O'Hagan, Leonard R Friedland, Emmanuel Hanon, Arnaud M Didierlaurent
In the last two decades, several vaccines formulated with a new generation of adjuvants have been licensed or approved to target diseases such as influenza, hepatitis B, cervical cancer, and malaria. These new generation adjuvants appear to work by delivering a localized activation signal to the innate immune system, which in turn promotes antigen-specific adaptive immunity. Advances in understanding of the innate immune system together with high-throughput discovery of synthetic immune potentiators are now expanding the portfolio of new generation adjuvants available for evaluation...
July 26, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28755541/vaccines-targeting-helper-t-cells-for-cancer-immunotherapy
#7
REVIEW
Marit Melssen, Craig L Slingluff
There are compelling arguments for designing cancer vaccines specifically to induce CD4(+) helper T cell responses. Recent studies highlight the crucial role of proliferating, activated effector memory Th1 CD4(+) T cells in effective antitumor immunity and reveal that CD4(+) T cells induce more durable immune-mediated tumor control than CD8(+) T cells. CD4(+) T cells promote antitumor immunity by numerous mechanisms including enhancing antigen presentation, co-stimulation, T cell homing, T cell activation, and effector function...
July 26, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28750280/tuberculosis-vaccines-perspectives-from-the-nih-niaid-mycobacteria-vaccine-testing-program
#8
REVIEW
Angelo A Izzo
The development of novel vaccine candidates against infections with Mycobacterium tuberculosis has highlighted our limited understanding of immune mechanisms required to kill M. tuberculosis. The induction of a Th1 immunity is vital, but new studies are required to identify other mechanisms that may be necessary. Novel vaccines formulations that invoke effector cells such as innate lymphoid cells may provide an environment that promote effector mechanisms including T cell and B cell mediated immunity. Identifying pathways associated with killing this highly successful infectious agent has become critical to achieving the goal of reducing the global tuberculosis burden...
July 24, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28750279/tnf-receptor-superfamily-agonists-as-molecular-adjuvants-for-cancer-vaccines
#9
REVIEW
Timothy Nj Bullock
Cancer vaccines have offered unrequited hope as a mechanism for rapidly and potently eliciting a patient's immune system to counter tumors. Initial results from preclinical mouse models have not translated to substantial benefit to patients, suggesting that either the targets or the vaccination approach were inadequate. Recent innovations in antigen identification have spiked renewed interest vaccination technologies. This has coincided with a detailed molecular understanding of the coordinated steps in postactivation support of T cell proliferation, differentiation and survival, leading to the development of novel targets and combinations that are substantially more effective than first and second generation cancer vaccines in preclinical models...
July 24, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28750261/mait-cells-in-infectious-diseases
#10
REVIEW
Marion Salou, Katarzyna Franciszkiewicz, Olivier Lantz
In humans, MAIT cells represent the most abundant T cell subset reacting against bacteria. Their frequency in the blood is decreased in a large variety of infectious diseases of either bacterial or viral origin. MAIT cells accumulate at the site of bacterial infection and are protective in experimental infection models. Recent epidemiological evidence supports an implication of MAIT cells in protecting against tuberculosis. MAIT cells can be activated either through direct recognition of microbial ligands or by inflammatory cytokines such as IL-12 and IL-18...
July 24, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28738289/germinal-center-enhancement-by-extended-antigen-availability
#11
REVIEW
Kimberly M Cirelli, Shane Crotty
Vaccine elicitation of protective antibody responses has proved difficult for a number of important human pathogens, including HIV-1. The amount of somatic hypermutation associated with the development of broadly neutralizing antibodies against HIV has not been achieved using conventional immunization strategies. An underexplored aspect of vaccine design is modulation of antigen kinetics. Immunization strategies with extended antigen availability have recently been shown to enhance humoral responses. In this review, we explore the mechanisms through which sustained antigen availability can enhance germinal center responses and the potency of antibody responses...
July 21, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28738211/the-immunopathology-of-dengue-and-zika-virus-infections
#12
REVIEW
Abigail Culshaw, Juthathip Mongkolsapaya, Gavin R Screaton
A large proportion of the world's population live in areas with dengue virus (DENV) transmission resulting in tens of millions of symptomatic dengue cases each year. Serious complications following DENV infection occur more frequently in those suffering from a second or subsequent infection implicating virus-specific immunity as having a role in pathogenesis. In recent years outbreaks of the related Zika virus (ZIKV) have been associated with birth defects and neurological complications. As DENV and ZIKV share a viral vector sequential infections can occur...
July 21, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28738209/psoriasis-a-mixed-autoimmune-and-autoinflammatory-disease
#13
REVIEW
Yun Liang, Mrinal K Sarkar, Lam C Tsoi, Johann E Gudjonsson
In recent years marked progress has been made in our understanding of the critical biologic and immunologic pathways involved in psoriasis. Genetic studies have demonstrated that susceptibility to psoriasis involves components of both the adaptive and innate immune system and not surprisingly activation of both of these arms of the immune system is found in psoriatic skin. While adaptive immune responses predominate in chronic plaque psoriasis, innate and autoinflammatory responses dominate in pustular forms of psoriasis, with other clinical subtypes extending on a spectrum between plaque and pustular psoriasis...
July 21, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28734176/cancer-immunotherapy-moving-forward-with-peptide-t-cell-vaccines
#14
REVIEW
Takumi Kumai, Aaron Fan, Yasuaki Harabuchi, Esteban Celis
Recent advances in cancer immunology, such as the discovery of immune checkpoint inhibitors, have validated immune cells as potential key players for effective cancer treatment. The efficacy of these therapies seems to be codependent on a tumor-reactive T lymphocyte response. For many years, numerous attempts and strategies in developing vaccines to generate tumor-reactive T cells have yielded poor results in the clinic due to suboptimal immunogenicity and the inability to overcome an immunosuppressive tumor microenvironment...
July 19, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28734175/cd8-t-cell-programming-by-cytomegalovirus-vectors-applications-in-prophylactic-and-therapeutic-vaccination
#15
REVIEW
Klaus Früh, Louis Picker
Vectors based on cytomegalovirus (CMV) represent a novel vaccine platform that maintains high frequencies of non-exhausted effector memory T cells in both CMV sero-positive and sero-negative individuals. In non-human primate models, CMV vectored vaccines provide unprecedented protection against simian immunodeficiency virus (SIV). Moreover, CMV vectors can be genetically altered to program highly diverse CD8+ T cell responses that differ in their epitope targeting including conventional, MHC-I restricted CD8+ T cells as well as unconventional CD8+ T cells restricted by MHC class II or non-polymorphic MHC-E...
July 19, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28734174/old-and-new-adjuvants
#16
REVIEW
Amy S McKee, Philippa Marrack
Adjuvants have been deliberately added to vaccines since the 1920's when alum was discovered to boost antibody responses, leading to better protection. The first adjuvants were discovered by accident and were used in the safer but less immunogenic subunit vaccines, supposedly by providing an antigen depot to extend antigen presentation. Since that time, much has been discovered about how these adjuvants impact cells at the tissue site to activate innate immune responses, mobilize dendritic cells and drive adaptive immunity...
July 19, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28732279/turbocharging-vaccines-emerging-adjuvants-for-dendritic-cell-based-therapeutic-cancer-vaccines
#17
REVIEW
Mansi Saxena, Nina Bhardwaj
Development of therapeutic cancer vaccines has been hindered by the many pro-tumorigenic mechanisms at play in cancer patients that serve to suppress both antigen presenting cells and T cells. In face of these obstacles, cancer vaccines are most likely to promote anti-tumorigenic immune responses only when formulated with strong adjuvants, and in combination with new immune interventions designed to reverse immune suppression and exhaustion of T cells in the tumor microenvironment. Dendritic cells (DCs) are often termed 'nature's adjuvant' due to their exceptional capacity for initiating both innate and adaptive immune responses...
July 18, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28728075/immunological-tolerance-as-a-barrier-to-protective-hiv-humoral-immunity
#18
REVIEW
Kristin Ms Schroeder, Amanda Agazio, Raul M Torres
HIV-1 infection typically eludes antibody control by our immune system and is not yet prevented by a vaccine. While many viral features contribute to this immune evasion, broadly neutralizing antibodies (bnAbs) against HIV-1 are often autoreactive and it has been suggested that immunological tolerance may restrict a neutralizing antibody response. Indeed, recent Ig knockin mouse studies have shown that bnAb-expressing B cells are largely censored by central tolerance in the bone marrow. However, the contribution of peripheral tolerance in limiting the HIV antibody response by anergic and potentially protective B cells is poorly understood...
July 17, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28728074/no-pain-no-gain-adjuvant-effects-of-alum-and-monophosphoryl-lipid-a-in-pertussis-and-hpv-vaccines
#19
REVIEW
Thomas C Mitchell, Carolyn R Casella
Development of non-infectious subunit vaccines is hampered by a slow pipeline of new adjuvants to replace or enhance alum in part because expectations of safety are high. Transient vaccine side effects are not clinical priorities because they cause no lasting harm and vaccine development has appropriately been focused on avoidance of serious adverse events. As a result, surprisingly little is known about the extent to which side effects caused by a vaccine's reactogencicity are predictive of successful immunization outcomes...
July 17, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28719821/bcg-old-workhorse-new-skills
#20
REVIEW
M Gengenbacher, N E Nieuwenhuizen, She Kaufmann
Bacille Calmette-Guérin (BCG), the only tuberculosis (TB) vaccine in clinical practice, has limitations in efficacy, immunogenicity and safety. Much current TB vaccine research focuses on engineering live mycobacteria to interfere with phagosome biology and host intracellular pathways including apoptosis and autophagy, with candidates such as BCG Δzmp1, BCG ΔureC::hly, BCG::ESX-1(Mmar), Mtb ΔphoP ΔfadD26, Mtb ΔRD1 ΔpanCD and M. smegmatis Δesx-3::esx-3(Mtb) in the development pipeline. Correlates of protection in preclinical studies include increased central memory CD4(+) T cells and recruitment of antigen-specific T cells to the lungs, with mucosal vaccination found to be superior to parenteral vaccination...
July 15, 2017: Current Opinion in Immunology
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