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Vaccines, Volume 3, Issue 2 (June 2015) – 14 articles , Pages 203-489

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420 KiB  
Review
The Promise of Preventive Cancer Vaccines
by Pier-Luigi Lollini, Federica Cavallo, Patrizia Nanni and Elena Quaglino
Vaccines 2015, 3(2), 467-489; https://doi.org/10.3390/vaccines3020467 - 17 Jun 2015
Cited by 35 | Viewed by 11027
Abstract
Years of unsuccessful attempts at fighting established tumors with vaccines have taught us all that they are only able to truly impact patient survival when used in a preventive setting, as would normally be the case for traditional vaccines against infectious diseases. While [...] Read more.
Years of unsuccessful attempts at fighting established tumors with vaccines have taught us all that they are only able to truly impact patient survival when used in a preventive setting, as would normally be the case for traditional vaccines against infectious diseases. While true primary cancer prevention is still but a long-term goal, secondary and tertiary prevention are already in the clinic and providing encouraging results. A combination of immunopreventive cancer strategies and recently approved checkpoint inhibitors is a further promise of forthcoming successful cancer disease control, but prevention will require a considerable reduction of currently reported toxicities. These considerations summed with the increased understanding of tumor antigens allow space for an optimistic view of the future. Full article
(This article belongs to the Special Issue Cancer Vaccines)
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423 KiB  
Review
Signaling Circuits and Regulation of Immune Suppression by Ovarian Tumor-Associated Macrophages
by Martin J. Cannon, Debopam Ghosh and Swetha Gujja
Vaccines 2015, 3(2), 448-466; https://doi.org/10.3390/vaccines3020448 - 29 May 2015
Cited by 18 | Viewed by 8197
Abstract
The barriers presented by immune suppression in the ovarian tumor microenvironment present one of the biggest challenges to development of successful tumor vaccine strategies for prevention of disease recurrence and progression following primary surgery and chemotherapy. New insights gained over the last decade [...] Read more.
The barriers presented by immune suppression in the ovarian tumor microenvironment present one of the biggest challenges to development of successful tumor vaccine strategies for prevention of disease recurrence and progression following primary surgery and chemotherapy. New insights gained over the last decade have revealed multiple mechanisms of immune regulation, with ovarian tumor-associated macrophages/DC likely to fulfill a central role in creating a highly immunosuppressive milieu that supports disease progression and blocks anti-tumor immunity. This review provides an appraisal of some of the key signaling pathways that may contribute to immune suppression in ovarian cancer, with a particular focus on the potential involvement of the c-KIT/PI3K/AKT, wnt/β-catenin, IL-6/STAT3 and AhR signaling pathways in regulation of indoleamine 2,3-dioxygenase expression in tumor-associated macrophages. Knowledge of intercellular and intracellular circuits that shape immune suppression may afford insights for development of adjuvant treatments that alleviate immunosuppression in the tumor microenvironment and enhance the clinical efficacy of ovarian tumor vaccines. Full article
(This article belongs to the Special Issue Cancer Vaccines)
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319 KiB  
Review
Emerging Vaccine Technologies
by Rebecca J. Loomis and Philip R. Johnson
Vaccines 2015, 3(2), 429-447; https://doi.org/10.3390/vaccines3020429 - 26 May 2015
Cited by 29 | Viewed by 8907
Abstract
Vaccination has proven to be an invaluable means of preventing infectious diseases by reducing both incidence of disease and mortality. However, vaccines have not been effectively developed for many diseases including HIV-1, hepatitis C virus (HCV), tuberculosis and malaria, among others. The emergence [...] Read more.
Vaccination has proven to be an invaluable means of preventing infectious diseases by reducing both incidence of disease and mortality. However, vaccines have not been effectively developed for many diseases including HIV-1, hepatitis C virus (HCV), tuberculosis and malaria, among others. The emergence of new technologies with a growing understanding of host-pathogen interactions and immunity may lead to efficacious vaccines against pathogens, previously thought impossible. Full article
(This article belongs to the Special Issue Vaccine Vector)
187 KiB  
Review
Integrating Immune Checkpoint Blockade with Anti-Neo/Mutated Antigens Reactivity to Increase the Clinical Outcome of Immunotherapy
by Giorgio Parmiani, Cristina Maccalli and Michele Maio
Vaccines 2015, 3(2), 420-428; https://doi.org/10.3390/vaccines3020420 - 21 May 2015
Cited by 16 | Viewed by 5891
Abstract
Antibodies to immune checkpoints have entered the clinical arena and have been shown to provide a clinical benefit for metastatic melanoma and, possibly, for other tumors as well. In this review paper we summarize this therapeutic activity and underline the functional mechanisms that [...] Read more.
Antibodies to immune checkpoints have entered the clinical arena and have been shown to provide a clinical benefit for metastatic melanoma and, possibly, for other tumors as well. In this review paper we summarize this therapeutic activity and underline the functional mechanisms that may be involved. Among them, we discuss the so far neglected role of tumor-associated antigens (TAAs) deriving from tumor somatic mutations and summarize the results of recent trials showing the immunogenic strength of such TAAs which can be specifically targeted by T cells activated by immune checkpoint antibodies. Finally we discuss new immunotherapy approaches that involve the combination of self/shared- or neo-TAAs-based vaccines and immune checkpoint blockade antibodies, to increase the clinical response of metastatic melanoma patients. Full article
(This article belongs to the Special Issue Cancer Vaccines)
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Review
Gavi HPV Programs: Application to Implementation
by Celina M. Hanson, Linda Eckert, Paul Bloem and Tania Cernuschi
Vaccines 2015, 3(2), 408-419; https://doi.org/10.3390/vaccines3020408 - 20 May 2015
Cited by 47 | Viewed by 11585
Abstract
Developing countries disproportionately suffer from the burden of cervical cancer yet lack the resources to establish systematic screening programs that have resulted in significant reductions in morbidity and mortality in developed countries. Human Papillomavirus (HPV) vaccination provides an opportunity for primary prevention of [...] Read more.
Developing countries disproportionately suffer from the burden of cervical cancer yet lack the resources to establish systematic screening programs that have resulted in significant reductions in morbidity and mortality in developed countries. Human Papillomavirus (HPV) vaccination provides an opportunity for primary prevention of cervical cancer in low-resource settings through vaccine provision by Gavi The Vaccine Alliance. In addition to the traditional national introduction, countries can apply for a demonstration program to help them make informed decisions for subsequent national introduction. This article summarizes information from approved Gavi HPV demonstration program proposals and preliminary implementation findings. After two rounds of applications, 23 countries have been approved targeting approximately 400,000 girls for vaccination. All countries are proposing primarily school-based strategies with mixed strategies to locate and vaccinate girls not enrolled in school. Experiences to date include: Reaching marginalized girls has been challenging; Strong coordination with the education sector is key and overall acceptance has been high. Initial coverage reports are encouraging but will have to be confirmed in population based coverage surveys that will take place later this year. Experiences from these countries are consistent with existing literature describing other HPV vaccine pilots in low-income settings. Full article
(This article belongs to the Special Issue Vaccine Delivery)
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318 KiB  
Review
CpG Oligonucleotides as Cancer Vaccine Adjuvants
by Hidekazu Shirota, Debra Tross and Dennis M. Klinman
Vaccines 2015, 3(2), 390-407; https://doi.org/10.3390/vaccines3020390 - 8 May 2015
Cited by 101 | Viewed by 10160
Abstract
Adjuvants improve host responsiveness to co-delivered vaccines through a variety of mechanisms. Agents that trigger cells expressing Toll-like receptors (TLR) activate an innate immune response that enhances the induction of vaccine-specific immunity. When administered in combination with vaccines designed to prevent or slow [...] Read more.
Adjuvants improve host responsiveness to co-delivered vaccines through a variety of mechanisms. Agents that trigger cells expressing Toll-like receptors (TLR) activate an innate immune response that enhances the induction of vaccine-specific immunity. When administered in combination with vaccines designed to prevent or slow tumor growth, TLR agonists have significantly improved the generation of cytotoxic T lymphocytes. Unfortunately, vaccines containing TLR agonists have rarely been able to eliminate large established tumors when administered systemically. To improve efficacy, attention has focused on delivering TLR agonists intra-tumorally with the intent of altering the tumor microenvironment. Agonists targeting TLRs 7/8 or 9 can reduce the frequency of Tregs while causing immunosuppressive MDSC in the tumor bed to differentiate into tumoricidal macrophages thereby enhancing tumor elimination. This work reviews pre-clinical and clinical studies concerning the utility of TLR 7/8/9 agonists as adjuvants for tumor vaccines. Full article
(This article belongs to the Special Issue Cancer Vaccines)
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Review
Influenza Vaccination Strategies: Comparing Inactivated and Live Attenuated Influenza Vaccines
by Saranya Sridhar, Karl A. Brokstad and Rebecca J. Cox
Vaccines 2015, 3(2), 373-389; https://doi.org/10.3390/vaccines3020373 - 24 Apr 2015
Cited by 136 | Viewed by 22034
Abstract
Influenza is a major respiratory pathogen causing annual outbreaks and occasional pandemics. Influenza vaccination is the major method of prophylaxis. Currently annual influenza vaccination is recommended for groups at high risk of complications from influenza infection such as pregnant women, young children, people [...] Read more.
Influenza is a major respiratory pathogen causing annual outbreaks and occasional pandemics. Influenza vaccination is the major method of prophylaxis. Currently annual influenza vaccination is recommended for groups at high risk of complications from influenza infection such as pregnant women, young children, people with underlying disease and the elderly, along with occupational groups such a healthcare workers and farm workers. There are two main types of vaccines available: the parenteral inactivated influenza vaccine and the intranasal live attenuated influenza vaccine. The inactivated vaccines are licensed from 6 months of age and have been used for more than 50 years with a good safety profile. Inactivated vaccines are standardized according to the presence of the viral major surface glycoprotein hemagglutinin and protection is mediated by the induction of vaccine strain specific antibody responses. In contrast, the live attenuated vaccines are licensed in Europe for children from 2–17 years of age and provide a multifaceted immune response with local and systemic antibody and T cell responses but with no clear correlate of protection. Here we discuss the immunological immune responses elicited by the two vaccines and discuss future work to better define correlates of protection. Full article
(This article belongs to the Special Issue Influenza Vaccines)
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444 KiB  
Review
Whole Tumor Antigen Vaccines: Where Are We?
by Cheryl Lai-Lai Chiang, George Coukos and Lana E. Kandalaft
Vaccines 2015, 3(2), 344-372; https://doi.org/10.3390/vaccines3020344 - 23 Apr 2015
Cited by 198 | Viewed by 13967
Abstract
With its vast amount of uncharacterized and characterized T cell epitopes available for activating CD4+ T helper and CD8+ cytotoxic lymphocytes simultaneously, whole tumor antigen represents an attractive alternative source of antigens as compared to tumor-derived peptides and full-length recombinant tumor [...] Read more.
With its vast amount of uncharacterized and characterized T cell epitopes available for activating CD4+ T helper and CD8+ cytotoxic lymphocytes simultaneously, whole tumor antigen represents an attractive alternative source of antigens as compared to tumor-derived peptides and full-length recombinant tumor proteins for dendritic cell (DC)-based immunotherapy. Unlike defined tumor-derived peptides and proteins, whole tumor lysate therapy is applicable to all patients regardless of their HLA type. DCs are essentially the master regulators of immune response, and are the most potent antigen-presenting cell population for priming and activating naïve T cells to target tumors. Because of these unique properties, numerous DC-based immunotherapies have been initiated in the clinics. In this review, we describe the different types of whole tumor antigens that we could use to pulse DCs ex vivo and in vivo. We also discuss the different routes of delivering whole tumor antigens to DCs in vivo and activating them with toll-like receptor agonists. Full article
(This article belongs to the Special Issue Dendritic Cell Vaccine)
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623 KiB  
Review
Vaccine Adjuvants: from 1920 to 2015 and Beyond
by Alberta Di Pasquale, Scott Preiss, Fernanda Tavares Da Silva and Nathalie Garçon
Vaccines 2015, 3(2), 320-343; https://doi.org/10.3390/vaccines3020320 - 16 Apr 2015
Cited by 470 | Viewed by 41134
Abstract
The concept of stimulating the body’s immune response is the basis underlying vaccination. Vaccines act by initiating the innate immune response and activating antigen presenting cells (APCs), thereby inducing a protective adaptive immune response to a pathogen antigen. Adjuvants are substances added to [...] Read more.
The concept of stimulating the body’s immune response is the basis underlying vaccination. Vaccines act by initiating the innate immune response and activating antigen presenting cells (APCs), thereby inducing a protective adaptive immune response to a pathogen antigen. Adjuvants are substances added to vaccines to enhance the immunogenicity of highly purified antigens that have insufficient immunostimulatory capabilities, and have been used in human vaccines for more than 90 years. While early adjuvants (aluminum, oil-in-water emulsions) were used empirically, rapidly increasing knowledge on how the immune system interacts with pathogens means that there is increased understanding of the role of adjuvants and how the formulation of modern vaccines can be better tailored towards the desired clinical benefit. Continuing safety evaluation of licensed vaccines containing adjuvants/adjuvant systems suggests that their individual benefit-risk profile remains favorable. Adjuvants contribute to the initiation of the innate immune response induced by antigens; exemplified by inflammatory responses at the injection site, with mostly localized and short-lived effects. Activated effectors (such as APCs) then move to draining lymph nodes where they direct the type, magnitude and quality of the adaptive immune response. Thus, the right match of antigens and adjuvants can potentiate downstream adaptive immune responses, enabling the development of new efficacious vaccines. Many infectious diseases of worldwide significance are not currently preventable by vaccination. Adjuvants are the most advanced new technology in the search for new vaccines against challenging pathogens and for vulnerable populations that respond poorly to traditional vaccines. Full article
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1053 KiB  
Review
Measuring Cellular Immunity to Influenza: Methods of Detection, Applications and Challenges
by Lynda Coughlan and Teresa Lambe
Vaccines 2015, 3(2), 293-319; https://doi.org/10.3390/vaccines3020293 - 14 Apr 2015
Cited by 27 | Viewed by 14923
Abstract
Influenza A virus is a respiratory pathogen which causes both seasonal epidemics and occasional pandemics; infection continues to be a significant cause of mortality worldwide. Current influenza vaccines principally stimulate humoral immune responses that are largely directed towards the variant surface antigens of [...] Read more.
Influenza A virus is a respiratory pathogen which causes both seasonal epidemics and occasional pandemics; infection continues to be a significant cause of mortality worldwide. Current influenza vaccines principally stimulate humoral immune responses that are largely directed towards the variant surface antigens of influenza. Vaccination can result in an effective, albeit strain-specific antibody response and there is a need for vaccines that can provide superior, long-lasting immunity to influenza. Vaccination approaches targeting conserved viral antigens have the potential to provide broadly cross-reactive, heterosubtypic immunity to diverse influenza viruses. However, the field lacks consensus on the correlates of protection for cellular immunity in reducing severe influenza infection, transmission or disease outcome. Furthermore, unlike serological methods such as the standardized haemagglutination inhibition assay, there remains a large degree of variation in both the types of assays and method of reporting cellular outputs. T-cell directed immunity has long been known to play a role in ameliorating the severity and/or duration of influenza infection, but the precise phenotype, magnitude and longevity of the requisite protective response is unclear. In order to progress the development of universal influenza vaccines, it is critical to standardize assays across sites to facilitate direct comparisons between clinical trials. Full article
(This article belongs to the Special Issue Influenza Vaccines)
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414 KiB  
Review
National Differences in Requirements for Ethical and Competent Authority Approval for a Multinational Vaccine Trial under the EU Directive 2001/20/EC
by Eva Van Doorn, Eelko Hak and Bob Wilffert
Vaccines 2015, 3(2), 263-292; https://doi.org/10.3390/vaccines3020263 - 14 Apr 2015
Cited by 3 | Viewed by 5721
Abstract
Obtaining approval for a multinational vaccine trial from an ethics committee and the national competent authority of different Member States of the European Union (EU) is challenging under clinical trial Directive 2001/20/EC because of the differences in the implementation of the directive in [...] Read more.
Obtaining approval for a multinational vaccine trial from an ethics committee and the national competent authority of different Member States of the European Union (EU) is challenging under clinical trial Directive 2001/20/EC because of the differences in the implementation of the directive in national laws of Member States. In this review the national differences in requirements for ethical and competent authority approval are illustrated. The national ethical and competent authority review procedures in Finland, Hungary, The Netherlands, Norway and Slovenia are described under the EU trial directive after discussing the provisions of the trial directive related to both review procedures. The review illustrates the differences between the countries in the documents that have to be submitted for the review procedures, the submission procedures and the language requirements of the documents, the organization of the ethics committees and the role of the competent authority in the approval procedure. Full article
430 KiB  
Review
Developing Universal Influenza Vaccines: Hitting the Nail, Not Just on the Head
by Lidewij C. M. Wiersma, Guus F. Rimmelzwaan and Rory D. De Vries
Vaccines 2015, 3(2), 239-262; https://doi.org/10.3390/vaccines3020239 - 26 Mar 2015
Cited by 41 | Viewed by 8759
Abstract
Influenza viruses have a huge impact on public health. Current influenza vaccines need to be updated annually and protect poorly against antigenic drift variants or novel emerging subtypes. Vaccination against influenza can be improved in two important ways, either by inducing more broadly [...] Read more.
Influenza viruses have a huge impact on public health. Current influenza vaccines need to be updated annually and protect poorly against antigenic drift variants or novel emerging subtypes. Vaccination against influenza can be improved in two important ways, either by inducing more broadly protective immune responses or by decreasing the time of vaccine production, which is relevant especially during a pandemic outbreak. In this review, we outline the current efforts to develop so-called “universal influenza vaccines”, describing antigens that may induce broadly protective immunity and novel vaccine production platforms that facilitate timely availability of vaccines. Full article
(This article belongs to the Special Issue Influenza Vaccines)
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658 KiB  
Article
Tattoo Delivery of a Semliki Forest Virus-Based Vaccine Encoding Human Papillomavirus E6 and E7
by Stephanie Van de Wall, Mateusz Walczak, Nienke Van Rooij, Baukje-Nynke Hoogeboom, Tjarko Meijerhof, Hans W. Nijman and Toos Daemen
Vaccines 2015, 3(2), 221-238; https://doi.org/10.3390/vaccines3020221 - 24 Mar 2015
Cited by 15 | Viewed by 8863
Abstract
The skin is an attractive organ for immunization because of the presence of antigen-presenting cells. Intradermal delivery via tattooing has demonstrated superior vaccine immunogenicity of DNA vaccines in comparison to conventional delivery methods. In this study, we explored the efficacy of tattoo injection [...] Read more.
The skin is an attractive organ for immunization because of the presence of antigen-presenting cells. Intradermal delivery via tattooing has demonstrated superior vaccine immunogenicity of DNA vaccines in comparison to conventional delivery methods. In this study, we explored the efficacy of tattoo injection of a tumor vaccine based on recombinant Semliki Forest virus replicon particles (rSFV) targeting human papillomavirus (HPV). Tattoo injection of rSFV particles resulted in antigen expression in both the skin and draining lymph nodes. In comparison with intramuscular injection, the overall antigen expression determined at the site of administration and draining lymph nodes was 10-fold lower upon tattoo injection. Delivery of SFV particles encoding the E6 and E7 antigens of human papillomavirus type 16 (SFVeE6,7) via tattooing resulted in HPV-specific cytotoxic T cells and in vivo therapeutic antitumor response. Strikingly, despite the observed lower overall transgene expression, SFVeE6,7 delivered via tattoo injection resulted in higher or equal levels of immune responses as compared to intramuscular injection. The intrinsic immunogenic potential of tattooing provides a benefit for immunotherapy based on an alphavirus. Full article
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Article
Epitope Prediction Assays Combined with Validation Assays Strongly Narrows down Putative Cytotoxic T Lymphocyte Epitopes
by Peng Peng Ip, Hans W. Nijman and Toos Daemen
Vaccines 2015, 3(2), 203-220; https://doi.org/10.3390/vaccines3020203 - 24 Mar 2015
Cited by 19 | Viewed by 7299
Abstract
Tumor vaccine design requires prediction and validation of immunogenic MHC class I epitopes expressed by target cells as well as MHC class II epitopes expressed by antigen-presenting cells essential for the induction of optimal immune responses. Epitope prediction methods are based on different [...] Read more.
Tumor vaccine design requires prediction and validation of immunogenic MHC class I epitopes expressed by target cells as well as MHC class II epitopes expressed by antigen-presenting cells essential for the induction of optimal immune responses. Epitope prediction methods are based on different algorithms and are instrumental for a first screening of possible epitopes. However, their results do not reflect a one-to-one correlation with experimental data. We combined several in silico prediction methods to unravel the most promising C57BL/6 mouse-restricted Hepatitis C virus (HCV) MHC class I epitopes and validated these epitopes in vitro and in vivo. Cytotoxic T lymphocyte (CTL) epitopes within the HCV non-structural proteins were identified, and proteasomal cleavage sites and helper T cell (Th) epitopes at close proximity to these CTL epitopes were analyzed using multiple prediction algorithms. This combined in silico analysis enhances the precision of identification of functional HCV-specific CTL epitopes. This approach will be applicable to the design of human vaccines not only for HCV, but also for other antigens in which T-cell responses play a crucial role. Full article
(This article belongs to the Special Issue Cancer Vaccines)
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