Therapeutic Advances in Vaccines and Immunotherapy最新文献

{"title":"Therapeutic vaccination immunomodulation: forming the basis of all cancer immunotherapy.","authors":"Brendon J Coventry","doi":"10.1177/2515135519862234","DOIUrl":"10.1177/2515135519862234","url":null,"abstract":"<p><p>Recent immunotherapy advances have convincingly demonstrated complete tumour removal with long-term survival. These impressive clinical responses have rekindled enthusiasm towards immunotherapy and tumour antigen vaccination providing 'cures' for melanoma and other cancers. However, many patients still do not benefit; sometimes harmed by severe autoimmune toxicity. Checkpoint inhibitors (anti-CTLA4; anti-PD-1) and interleukin-2 (IL-2) are 'pure immune drivers' of pre-existing immune responses and can induce either desirable effector-stimulatory or undesirable inhibitory-regulatory responses. Why some patients respond well, while others do not, is presently unknown, but might be related to the cellular populations being 'driven' at the time of dosing, dictating the resulting immune response. Vaccination is in-vivo immunotherapy requiring an active host response. Vaccination for cancer treatment has been skeptically viewed, arising partially from difficulty demonstrating clear, consistent clinical responses. However, this article puts forward accumulating evidence that 'vaccination' immunomodulation constitutes the fundamental, central, intrinsic property associated with antigen exposure not only from exogenous antigen (allogeneic or autologous) administration, but also from endogenous release of tumour antigen (autologous) from in-vivo tumour-cell damage and lysis. Many 'standard' cancer therapies (chemotherapy, radiotherapy etc.) create waves of tumour-cell damage, lysis and antigen release, thus constituting 'in-vivo vaccination' events. In essence, whenever tumour cells are killed, antigen release can provide in-vivo repeated vaccination events. Effective anti-tumour immune responses require antigen release/supply; immune recognition, and immune responsiveness. With better appreciation of endogenous vaccination and immunomodulation, more refined approaches can be engineered with prospect of higher success rates from cancer therapy, including complete responses and better survival rates.</p>","PeriodicalId":33285,"journal":{"name":"Therapeutic Advances in Vaccines and Immunotherapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/bf/36/10.1177_2515135519862234.PMC6676259.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41214730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A review of H5Nx avian influenza viruses.","authors":"Ivette A Nuñez,&nbsp;Ted M Ross","doi":"10.1177/2515135518821625","DOIUrl":"10.1177/2515135518821625","url":null,"abstract":"<p><p>Highly pathogenic avian influenza viruses (HPAIVs), originating from the A/goose/Guangdong/1/1996 H5 subtype, naturally circulate in wild-bird populations, particularly waterfowl, and often spill over to infect domestic poultry. Occasionally, humans are infected with HPAVI H5N1 resulting in high mortality, but no sustained human-to-human transmission. In this review, the replication cycle, pathogenicity, evolution, spread, and transmission of HPAIVs of H5Nx subtypes, along with the host immune responses to Highly Pathogenic Avian Influenza Virus (HPAIV) infection and potential vaccination, are discussed. In addition, the potential mechanisms for Highly Pathogenic Avian Influenza Virus (HPAIV) H5 Reassorted Viruses H5N1, H5N2, H5N6, H5N8 (H5Nx) viruses to transmit, infect, and adapt to the human host are reviewed.</p>","PeriodicalId":33285,"journal":{"name":"Therapeutic Advances in Vaccines and Immunotherapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2515135518821625","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37023996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Burden, effectiveness and safety of influenza vaccines in elderly, paediatric and pregnant populations.","authors":"Sheena G Sullivan, Olivia H Price, Annette K Regan","doi":"10.1177/2515135519826481","DOIUrl":"10.1177/2515135519826481","url":null,"abstract":"<p><p>Vaccination is the most practical means available for preventing influenza. Influenza vaccines require frequent updates to keep pace with antigenic drift of the virus, and the effectiveness, and sometimes the safety, of the vaccine can therefore vary from season to season. Three key populations that the World Health Organization recommends should be prioritized for influenza vaccination are pregnant women, children younger than 5 years of age and the elderly. This review discusses the burden of influenza and the safety and effectiveness profile of influenza vaccines recommended for these groups.</p>","PeriodicalId":33285,"journal":{"name":"Therapeutic Advances in Vaccines and Immunotherapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/50/7f/10.1177_2515135519826481.PMC6376509.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36988830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer stem cell mobilization and therapeutic targeting of the 5T4 oncofetal antigen.","authors":"Richard Harrop, Eric O'Neill, Peter L Stern","doi":"10.1177/2515135518821623","DOIUrl":"10.1177/2515135518821623","url":null,"abstract":"<p><p>Cancer stem cells (CSCs) can act as the cellular drivers of tumors harnessing stem cell properties that contribute to tumorigenesis either as founder elements or by the gain of stem cell traits by the malignant cells. Thus, CSCs can self-renew and generate the cellular heterogeneity of tumors including a hierarchical organization similar to the normal tissue. While the principle tumor growth contribution is often from the non-CSC components, it is the ability of small numbers of CSCs to avoid the effects of therapeutic strategies that can contribute to recurrence after treatment. However, identifying and characterizing CSCs for therapeutic targeting is made more challenging by their cellular potency being influenced by a particular tissue niche or by the capacity of more committed cells to regain stem cell functions. This review discusses the properties of CSCs including the limitations of the available cell surface markers, the assays that document tumor initiation and clonogenicity, the roles of epithelial mesenchymal transition and molecular pathways such as Notch, Wnt, Hippo and Hedgehog. The ability to target and eliminate CSCs is thought to be critical in the search for curative cancer treatments. The oncofetal tumor-associated antigen 5T4 (TBGP) has been linked with CSC properties in several different malignancies. 5T4 has functional attributes that are relevant to the spread of tumors including through EMT, CXCR4/CXCL12, Wnt, and Hippo pathways which may all contribute through the mobilization of CSCs. There are several different immunotherapies targeting 5T4 in development including antibody-drug conjugates, antibody-targeted bacterial super-antigens, a Modified Vaccinia Ankara-basedvaccine and 5T4-directed chimeric antigen receptor T-cells. These immune therapies would have the advantage of targeting both the bulk tumor as well as mobilized CSC populations.</p>","PeriodicalId":33285,"journal":{"name":"Therapeutic Advances in Vaccines and Immunotherapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d0/9b/10.1177_2515135518821623.PMC6348545.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36929039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Active surveillance of adverse events following immunization (AEFI): a prospective 3-year vaccine safety study","authors":"J. Sebastian, P. Gurumurthy, M. Ravi, M. Ramesh","doi":"10.1177/2515135519889000","DOIUrl":"https://doi.org/10.1177/2515135519889000","url":null,"abstract":"Background: Vaccines used in national immunization programs are considered safe and effective but immunization safety has become as important as the efficacy of vaccination programs. The objective of the study was to detect adverse events following immunization (AEFIs) to all vaccines administered to a pediatric population in India. Methods: The prospective active vaccine safety surveillance study enrolled eligible children in the age group 0–5 years receiving vaccination from the immunization center at JSS Hospital, Mysuru. Study participants were monitored at the site for 30 min following vaccination and a telephonic survey was made after 8 days to identify all AEFIs. Causality assessment of the AEFIs were done using a new algorithm developed by the safety and vigilance department of the World Health Organization. Results: The incidence of reported AEFIs was 13.7%. The most frequently reported AEFI was fever (n = 3095, 93.2%) with an incidence of 109.7 per 1000 doses of vaccine administered, followed by persistent crying (n = 69, 2.4 per 1000 doses of vaccine) and diarrhea (n = 57, 2.0 per 1000 doses of vaccine). The majorly implicated vaccine for AEFIs was Pentavac® followed by BCG. Consistent causal association to immunization was observed in 93.4% of cases. Conclusions: A high incidence rate of AEFI was observed in our study population when compared with previous published studies. AEFI surveillance studies help to detect changes in the frequency of adverse events, which may be an alert to consider vaccine quality or identify a specific risk among the local population.","PeriodicalId":33285,"journal":{"name":"Therapeutic Advances in Vaccines and Immunotherapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2515135519889000","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45617284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights into innate and adaptive immune responses in vaccine development against EV-A71","authors":"Hui Xuan Lim, C. Poh","doi":"10.1177/2515135519888998","DOIUrl":"https://doi.org/10.1177/2515135519888998","url":null,"abstract":"Enterovirus A71 (EV-A71) is one of the major causative agents of hand, foot and mouth disease (HFMD) in the world, infecting mostly infants and young children (<5 years of age) in Asia. Approximately 2 million cases of HFMD were reported in China each year, of which approximately 45–50% were due to EV-A71. Most of the HFMD infections caused by EV-A71 usually result in mild symptoms with rashes and ulcers in the mouth. However, virulent strains of EV-A71 can infect the central nervous system and cause severe neurologic diseases, leading to reduced cognitive ability, acute flaccid paralysis and death. The lack of understanding of cellular immunity for long-term protection from the HFMD disease represents a major obstacle for vaccine development. In particular, the role of innate and T cell immunity during HFMD infection remains unclear and there is evidence suggesting the importance of CD4+ and CD8+ T cells for protective immunity. Currently, no US FDA-approved vaccine is available for EV-A71. Although the inactivated vaccines produced in China are highly effective (vaccine efficacy >95%), they lack the cellular immunity required for long-term protection. In this review, we discuss the findings that support the protective roles of innate and T cell immunity against EV-A71 infection, which will provide the knowledge needed for the urgent development of efficacious vaccines that will confer long-term protection.","PeriodicalId":33285,"journal":{"name":"Therapeutic Advances in Vaccines and Immunotherapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2515135519888998","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49129158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The failure of radical treatments to cure cancer: can less deliver more?","authors":"Angus G Dalgleish,&nbsp;Peter L Stern","doi":"10.1177/2515135518815393","DOIUrl":"https://doi.org/10.1177/2515135518815393","url":null,"abstract":"<p><p>All too often attempts to deliver improved cancer cure rates by increasing the dose of a particular treatment are not successful enough to justify the accompanying increase in toxicity and reduction in quality of life suffered by a significant number of patients. In part, this drive for using higher levels of treatment derives from the nature of the process for testing and incorporation of new protocols. Indeed, new treatment regimens must now consider the key role of immunity in cancer control, a component that has been largely ignored until very recently. The recognition that some drugs developed for cytotoxicity at higher doses can display alternative anticancer activities at lower doses including through modulation of immune responses is prompting a significant re-evaluation of treatment protocol development. Given that tumours are remarkably heterogeneous and with inherent genetic instability it is probably only the adaptive immune response with its flexibility and extensive repertoire that can rise to the challenge of effecting significant control and ultimately elimination of a patient's cancer. This article discusses some of the elements that have limited higher levels of treatment outcomes and where too much proved less effective. We explore observations that less can often be as effective, if not more effective especially with some chemotherapy regimens, and discuss how this can be exploited in combination with immunotherapies to deliver nontoxic improved tumour responses.</p>","PeriodicalId":33285,"journal":{"name":"Therapeutic Advances in Vaccines and Immunotherapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2515135518815393","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36835845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Broadly neutralizing antibodies in HIV-1 treatment and prevention.","authors":"Rajesh Kumar,&nbsp;Huma Qureshi,&nbsp;Suprit Deshpande,&nbsp;Jayanta Bhattacharya","doi":"10.1177/2515135518800689","DOIUrl":"https://doi.org/10.1177/2515135518800689","url":null,"abstract":"<p><p>Antibodies that naturally develop in some individuals infected with human immunodeficiency virus 1 (HIV-1) and are capable of broadly neutralizing diverse strains of HIV-1 are useful for two applications: they can inform the rational design of vaccine immunogens, and they may be capable of preventing and treating HIV-1 infection when administered passively. A phase IIb study has been initiated with the experimental broadly neutralizing antibody (bnAb) VRC01, which has considerable breadth and potency (also referred to as a phase IIb HVTN 703/HPTN 081 and HVTN 704/HPTN 085 AMP efficacy trials) to evaluate its protective efficacy in individuals at risk of HIV acquisition. bnAbs prevent HIV-1 infection by selectively targeting vulnerable sites on the viral envelope (Env) protein that facilitates the entry of HIV. Although in very early stages, bnAbs capable of neutralizing a broad range of inter- and intraclade HIV-1 isolates have been demonstrated to have potential in treating patients either alone or in combination with antiretroviral drug therapy (cART); however, they are proposed to be advantageous over the latter as far as durability and side effects are concerned. Recent studies have indicated that combination therapy of potent bnAbs along with latency-reversing agents (LRAs) might also target latent reservoirs of HIV and kill them by recruiting effector cells, such as natural killer cells, thus confirming clinical progression. Possession of such qualities makes these new-generation potent bnAbs extremely valuable in effectively complementing the shortcomings of current ART drugs and improving the quality of life of infected individuals.</p>","PeriodicalId":33285,"journal":{"name":"Therapeutic Advances in Vaccines and Immunotherapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2515135518800689","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36604739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimal use of meningococcal serogroup B vaccines: moving beyond outbreak control.","authors":"Paul Balmer,&nbsp;Laura J York","doi":"10.1177/2515135518781757","DOIUrl":"https://doi.org/10.1177/2515135518781757","url":null,"abstract":"<p><p><i>Neisseria meningitidis</i> is a major cause of meningitis and septicemia globally. Vaccines directed against <i>N. meningitidis</i> serogroup B (MenB) have been used to control sporadic and sustained disease in industrialized and non-industrialized countries. Early outer membrane vesicle (OMV) vaccines effectively reduced MenB disease in countries such as Norway, New Zealand, and France; however, these vaccines were highly specific for their targeted outbreak strain, did not elicit a durable immune response, and were ineffective for widespread use due to the diversity of MenB-disease-causing isolates. Recently developed recombinant protein-based MenB vaccines that target conserved surface proteins have the potential to induce a broader immune response against the diversity of disease-causing strains. Given the deleterious consequences and sporadic nature of MenB disease, the use of optimal vaccination strategies is crucial for prevention. Reactive vaccination strategies used in the past have significant limitations, including delayed implementation, substantial use of resources, and time constraints. The broad coverage potential of recombinant protein-based MenB vaccines suggests that routine use could result in a reduced burden of disease. Despite this, routine use of MenB vaccines is currently limited in practice.</p>","PeriodicalId":33285,"journal":{"name":"Therapeutic Advances in Vaccines and Immunotherapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2515135518781757","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36463187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel tumour antigens and the development of optimal vaccine design.","authors":"Victoria A Brentville, Suha Atabani, Katherine Cook, Lindy G Durrant","doi":"10.1177/2515135518768769","DOIUrl":"10.1177/2515135518768769","url":null,"abstract":"<p><p>The interplay between tumours and the immune system has long been known to involve complex interactions between tumour cells, immune cells and the tumour microenvironment. The progress of checkpoint inhibitors in the clinic in the last decade has highlighted again the role of the immune system in the fight against cancer. Numerous efforts have been undertaken to develop ways of stimulating the cellular immune response to eradicate tumours. These interventions include the identification of appropriate tumour antigens as targets for therapy. In this review, we summarize progress in selection of target tumour antigen. Targeting self antigens has the problem of thymic deletion of high-affinity T-cell responses leaving a diminished repertoire of low-affinity T cells that fail to kill tumour cells. Thymic regulation appears to be less stringent for differentiation of cancer-testis antigens, as many tumour rejection antigens fall into this category. More recently, targeting neo-epitopes or post-translational modifications such as a phosphorylation or stress-induced citrullination has shown great promise in preclinical studies. Of particular interest is that the responses can be mediated by both CD4 and CD8 T cells. Previous vaccines have targeted CD8 T-cell responses but more recently, the central role of CD4 T cells in orchestrating inflammation within tumours and also differentiating into potent killer cells has been recognized. The design of vaccines to induce such immune responses is discussed herein. Liposomally encoded ribonucleic acid (RNA), targeted deoxyribonucleic acid (DNA) or long peptides linked to toll-like receptor (TLR) adjuvants are the most promising new vaccine approaches. These exciting new approaches suggest that the 'Holy Grail' of a simple nontoxic cancer vaccine may be on the horizon. A major hurdle in tumour therapy is also to overcome the suppressive tumour environment. We address current progress in combination therapies and suggest that these are likely to show the most promise for the future.</p>","PeriodicalId":33285,"journal":{"name":"Therapeutic Advances in Vaccines and Immunotherapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5933538/pdf/10.1177_2515135518768769.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36306491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}