Showing papers in "Human Vaccines & Immunotherapeutics in 2017"
TL;DR: This review focuses on identifying the mechanisms through which TGF-β is involved in tumorigenesis and current therapeutics that are under development.
Abstract: Transforming growth factor-β (TGF-β) regulates cell growth and differentiation, apoptosis, cell motility, extracellular matrix production, angiogenesis, and cellular immunity. It has a paradoxical role in cancer. In the early stages it inhibits cellular transformation and prevents cancer progression. In later stages TGF-β plays a key role in promoting tumor progression through mainly 3 mechanisms: facilitating epithelial to mesenchymal transition, stimulating angiogenesis and inducing immunosuppression. As a result of its opposing tumor promoting and tumor suppressive abilities, TGF-β and its pathway has represented potential opportunities for drug development and several therapies targeting the TGF-β pathway have been identified. This review focuses on identifying the mechanisms through which TGF-β is involved in tumorigenesis and current therapeutics that are under development.
169 citations
TL;DR: This work states that aluminum, the first adjuvant in human vaccines, proved insufficient to develop vaccines that could protect against new challenging pathogens such as HIV and malaria, and opens the door to more rational vaccine design with implications for developing new and better vaccines.
Abstract: Adjuvants are substances added to vaccines to improve their immunogenicity. Used for more than 80 years, aluminum, the first adjuvant in human vaccines, proved insufficient to develop vaccines that could protect against new challenging pathogens such as HIV and malaria. New adjuvants and new combinations of adjuvants (Adjuvant Systems) have opened the door to the delivery of improved and new vaccines against re-emerging and difficult pathogens. Adjuvant Systems concept started through serendipity. The access to new developments in technology, microbiology and immunology have been instrumental for the dicephering of what they do and how they do it. This knowledge opens the door to more rational vaccine design with implications for developing new and better vaccines.
162 citations
TL;DR: Advances in DNA vaccine vector design, the inclusion of genetically engineered cytokine adjuvants, and novel non-mechanical delivery methods show promise for increasing the immunogenicity of DNA vaccines.
Abstract: A major advantage of DNA vaccination is the ability to induce both humoral and cellular immune responses. DNA vaccines are currently used in veterinary medicine, but have not achieved widespread acceptance for use in humans due to their low immunogenicity in early clinical studies. However, recent clinical data have re-established the value of DNA vaccines, particularly in priming high-level antigen-specific antibody responses. Several approaches have been investigated for improving DNA vaccine efficacy, including advancements in DNA vaccine vector design, the inclusion of genetically engineered cytokine adjuvants, and novel non-mechanical delivery methods. These strategies have shown promise, resulting in augmented adaptive immune responses in not only mice, but also in large animal models. Here, we review advancements in each of these areas that show promise for increasing the immunogenicity of DNA vaccines.
146 citations
TL;DR: All the marketed vaccines belong to the JEV genotype III, but have been shown to be efficacious against other genotypes and strains, with varying degrees of cross-neutralization, albeit at levels deemed to be protective.
Abstract: Japanese encephalitis (JE) is a serious public health concern in most of Asia. The disease is caused by JE virus (JEV), a flavivirus transmitted by Culex mosquitoes. Several vaccines have been developed to control JE in endemic areas as well as to protect travelers and military personnel who visit or are commissioned from non-endemic to endemic areas. The vaccines include inactivated vaccines produced in mouse brain or cell cultures, live attenuated vaccines, and a chimeric vaccine based on the live attenuated yellow fever virus 17D vaccine strain. All the marketed vaccines belong to the JEV genotype III, but have been shown to be efficacious against other genotypes and strains, with varying degrees of cross-neutralization, albeit at levels deemed to be protective. The protective responses have been shown to last three or more years, depending on the type of vaccine and the number of doses. This review presents a brief account of the different JE vaccines, their immunogenicity and protective ability, and the impact of JE vaccines in reducing the burden of disease in endemic countries.
99 citations
TL;DR: Particular focus should be brought to designing delivery strategies that take into account the broad range of diseases, populations and healthcare delivery settings that stand to benefit from this unique mucosal route.
Abstract: Nasal delivery offers many benefits over traditional approaches to vaccine administration. These include ease of administration without needles that reduces issues associated with needlestick injuries and disposal. Additionally, this route offers easy access to a key part of the immune system that can stimulate other mucosal sites throughout the body. Increased acceptance of nasal vaccine products in both adults and children has led to a burgeoning pipeline of nasal delivery technology. Key challenges and opportunities for the future will include translating in vivo data to clinical outcomes. Particular focus should be brought to designing delivery strategies that take into account the broad range of diseases, populations and healthcare delivery settings that stand to benefit from this unique mucosal route.
99 citations
TL;DR: It is suggested that HPV vaccine refusal is common among parents of adolescents and may have increased relative to previous estimates, and targeted communication strategies may be needed to effectively address HPV vaccine hesitancy.
Abstract: Background: We sought to estimate the national prevalence of HPV vaccine refusal and delay in a nationally-representative sample of parents of adolescents. We also compared parents who refused versus delayed HPV vaccine in terms of their vaccination beliefs and clinical communication preferences. Methods: In 2014 to 2015, we conducted an online survey of 1,484 US parents who reported on an 11- to 17-year-old child in their household. We used weighted multinomial logistic regression to assess correlates of HPV vaccine refusal and delay. Results: Overall, 28% of parents reported that they had ever “refused or decided not to get” HPV vaccine for their child, and an additional 8% of parents reported that they had “delayed or put off getting” HPV vaccine. Compared to no refusal/delay, refusal was associated with lower confidence in adolescent vaccination (relative risk ratio [RRR] = 0.66, 95% confidence interval [CI], 0.48–0.91), lower perceived HPV vaccine effectiveness (RRR = 0.68, 95% CI, 0.50–0.91)...
89 citations
TL;DR: To foster improvements in HPV vaccine uptake and reduce disparities in HPV associated cancers, future interventions must target men and minority populations, for whom knowledge gaps exist.
Abstract: Purpose: Gaps remain in the public's knowledge of the human papillomavirus (HPV). We assessed racial/ethnic and gender disparities in knowledge and awareness of HPV and the HPV vaccine among US adults.Methods: Data from the Health Information National Trends Survey 4 Cycle 3 (September – December 2013) and Cycle 4 (August – November 2014) were analyzed for 6,862 respondents aged 18 years and older. Weighted multivariable logistic regression models were used to estimate racial/ethnic and gender disparities in HPV knowledge and HPV vaccination awareness.Results: Sixty-six percent of respondents had heard of HPV and the HPV vaccine (57% of men vs. 75% of women). In multivariable analyses, compared with men, women were 225% (95% CI: 2.60 – 4.07) more likely to have heard of HPV, and 281% (95% CI: 3.06 – 4.74) more likely to have heard of the HPV vaccine. Non-Hispanic Blacks were 33% (95% CI: 0.47 – 0.96) and 44% (95% CI: 0.39 – 0.81) less likely than non-Hispanic Whites to have heard of HPV and the ...
89 citations
TL;DR: Palivizumab prophylaxis is mainly limited to selected high-risk infants for the first RSV season, and concerns have been raised regarding cost-effectiveness of palivIZumab.
Abstract: Respiratory syncytial virus (RSV) accounts for about 20% of all respiratory infections in children below the age of 5 y. It is associated with up to 63% of all acute respiratory infections and up t...
84 citations
TL;DR: The rationale for various therapeutic combinations, clinical trial experiences, and future directions are reviewed, and the most promising developments that could lead to approval of novel therapeutic cancer vaccines are highlighted.
Abstract: Therapeutic cancer vaccines have gained significant popularity in recent years as new approaches for specific oncologic indications emerge. Three therapeutic cancer vaccines are FDA approved and one is currently approved by the EMA as monotherapy with modest treatment effects. Combining therapeutic cancer vaccines with other treatment modalities like radiotherapy (RT), hormone therapy, immunotherapy, and/or chemotherapy have been investigated as a means to enhance immune response and treatment efficacy. There is growing preclinical and clinical data that combination of checkpoint inhibitors and vaccines can induce immunogenic intensification with favorable outcomes. Additionally, novel methods for identifying targetable neoantigens hold promise for personalized vaccine development. In this article, we review the rationale for various therapeutic combinations, clinical trial experiences, and future directions. We also highlight the most promising developments that could lead to approval of novel therapeutic cancer vaccines.
84 citations
TL;DR: Present data indicate that tumor infiltration by lymphocytes can be induced by dentritic cell immunotherapy and that this may positively affect clinical outcome.
Abstract: Autologous dentritic cell immunotherapy has been proven effective in treating tumors outside the central nervous system. Current evidence from phase I and II trials suggest a similar efficacy for central nervous system tumors as well and that an active immune response against these tumors can be generated. We aim to review the literature to identify the types of immune responses against gliomas found to be generated by dendritic cell vaccinations and the types of immune cells subsequently infiltrating the glioma microenvironment. A systematic review of the literature was performed by searching the online databases PubMEd, Google Scholar, and EMBASE with use of the keywords intratumoral, infiltration, lymphocytic, vaccination and gliomas. Seven studies reporting lymphocytic infiltration of gliomas microenvironment were identified. Three studies (42.8%) reported presence of tumor infiltrating lymphocytes in 50%, 50% and 28.6% of included patients respectively in the post-vaccination specimens that were not present in the pre-vaccination samples. The remaining 4 (57.2%) reported an up to 6-fold increase in the number of pre-existing lymphocytes following vaccination. Present data indicate that tumor infiltration by lymphocytes can be induced by dentritic cell immunotherapy and that this may positively affect clinical outcome. It still remains unclear which factors influence the above reaction and therefore prediction of response to treatment is still not possible.
80 citations
TL;DR: The role of IL-12, IL-23, and IL-17 in the pathogenesis of psoriasis and the monoclonal antibodies that target these cytokines in the treatment of this disease are reviewed.
Abstract: Psoriasis is a chronic, inflammatory, immune-mediated skin condition that affects 3 to 4% of the adult US population, characterized by well-demarcated, erythematous plaques with silver scale. Psoriasis is associated with many comorbidities including cardiometabolic disease and can have a negative impact on quality of life. The current armamentarium of psoriasis treatment includes topical therapies, phototherapy, oral immunosuppressive therapies, and biologic agents. Over the past 2 decades, there has been rapid development of novel biologic therapies for the treatment of moderate-to-severe plaque psoriasis. This article will review the role of IL-12, IL-23, and IL-17 in the pathogenesis of psoriasis and the monoclonal antibodies (ustekinumab, secukinumab, ixekizumab, brodalumab, guselkumab, tildrakizumab, and risankizumab) that target these cytokines in the treatment of this disease.
TL;DR: Health literacy is defined as “the degree to which individuals have the capacity to obtain, process, and understand basic health information and services needed to make appropriate health decisions” and adults with low health literacy skills are less likely to use preventive services.
Abstract: Health literacy is defined as “the degree to which individuals have the capacity to obtain, process, and understand basic health information and services needed to make appropriate health decisions...
TL;DR: The prospects for a preventive HIV vaccine have never been more promising with on-going optimization of prime/boost strategies, the development of mosaic immunogens, replication competent vectors, and emergence of new strategies designed to induce bnAb.
Abstract: An HIV-1 vaccine is needed to curtail the HIV epidemic. Only one (RV144) out of the 6 HIV-1 vaccine efficacy trials performed showed efficacy. A potential mechanism of protection is the induction of functional antibodies to V1V2 region of HIV envelope. The 2 main current approaches to the generation of protective immunity are through broadly neutralizing antibodies (bnAb) and induction of functional antibodies (non-neutralizing Abs with other potential anti-viral functions). Passive immunization using bnAb has advanced into phase II clinical trials. The induction of bnAb using mimics of the natural Env trimer or B-cell lineage vaccine design is still in pre-clinical phase. An attempt at optimization of protective functional antibodies will be assessed next with the efficacy trial (HVTN702) about to start. With on-going optimization of prime/boost strategies, the development of mosaic immunogens, replication competent vectors, and emergence of new strategies designed to induce bnAb, the prospects for a preventive HIV vaccine have never been more promising.
TL;DR: The data indicate that the vaccine is safe and induces strong humoral and cellular immune response in up to 100 % of healthy adult volunteers, and provide a rationale for testing efficacy in Phase III trials.
Abstract: Ebola hemorrhagic fever, also known as Ebola virus disease or EVD, is one of the most dangerous viral diseases in humans and animals. In this open-label, dose-escalation clinical trial, we assessed the safety, side effects, and immunogenicity of a novel, heterologous prime-boost vaccine against Ebola, which was administered in 2 doses to 84 healthy adults of both sexes between 18 and 55 years. The vaccine consists of live-attenuated recombinant vesicular stomatitis virus (VSV) and adenovirus serotype-5 (Ad5) expressing Ebola envelope glycoprotein. The most common adverse event was pain at the injection site, although no serious adverse events were reported. The vaccine did not significantly impact blood, urine, and immune indices. Seroconversion rate was 100 %. Antigen-specific IgG geometric mean titer at day 42 was 3,277 (95 % confidence interval 2,401–4,473) in volunteers immunized at full dose. Neutralizing antibodies were detected in 93.1 % of volunteers immunized at full dose, with geometric ...
TL;DR: Updated recommendations on prevention of infectious diseases in AH adult patients are provided to supply a useful and practical tool to healthcare workers for the management of these subjects, in hospital setting and in outpatients consultation.
Abstract: Asplenic or hyposplenic (AH) individuals are particularly vulnerable to invasive infections caused by encapsulated bacteria. Such infections have often a sudden onset and a fulminant course. Infect...
TL;DR: This article provides the most comprehensive analysis to date of the factors contributing to CAP in children under 5 y of age and suggests vaccines should be introduced into Chinese immunization programs, and further economic evaluations should be conducted.
Abstract: Background: The aim of this systematic review was to examine the etiology of community-acquired pneumonia (CAP) among Chinese children younger than 5 y and provide evidence for further cost-effecti...
TL;DR: It is important for those supporting vaccination to be aware of, examine, and counter the claims of organized anti-vaccination groups, which are a platform that promotes misleading information.
Abstract: In 2014, a large measles outbreak swept through the Disneyland theme park in California, infecting over 50 people.1 Several of the children who initially spread the disease were intentionally left ...
TL;DR: The 2014–15 Ebola outbreak in West Africa highlighted the potential for large disease outbreaks caused by emerging pathogens and has generated considerable focus on preparedness for future epidemics, and work is already underway to develop vaccines against a number of other outbreak pathogens.
Abstract: The 2014–15 Ebola outbreak in West Africa highlighted the potential for large disease outbreaks caused by emerging pathogens and has generated considerable focus on preparedness for future epidemic...
TL;DR: How often people search the Internet for vaccination-related information is investigated, if this search is spontaneous or induced by media, and which kind of information is in particular searched, to monitor the interest for preventable infections and related vaccines.
Abstract: Nowadays, more and more people surf the Internet seeking health-related information. Information and communication technologies (ICTs) can represent an important opportunities in the field of Publi...
TL;DR: The impact of process stresses on vaccine integrity, the application of excipients in spray drying of vaccines, process and formulation optimization strategies based on Design of Experiment approaches as well as opportunities for future application of spray dried vaccine powders for vaccine delivery are discussed.
Abstract: Spray drying is a promising method for the stabilization of vaccines, which are usually formulated as liquids. Usually, vaccine stability is improved by spray drying in the presence of a range of excipients. Unlike freeze drying, there is no freezing step involved, thus the damage related to this step is avoided. The edge of spray drying resides in its ability for particles to be engineered to desired requirements, which can be used in various vaccine delivery methods and routes. Although several spray dried vaccines have shown encouraging preclinical results, the number of vaccines that have been tested in clinical trials is limited, indicating a relatively new area of vaccine stabilization and delivery. This article reviews the current status of spray dried vaccine formulations and delivery methods. In particular it discusses the impact of process stresses on vaccine integrity, the application of excipients in spray drying of vaccines, process and formulation optimization strategies based on Design of Experiment approaches as well as opportunities for future application of spray dried vaccine powders for vaccine delivery.
TL;DR: Most of the videos were positive in tone, but those that disapproved of immunization were the most liked and shared and what influences public opinions to use communication strategies more effectively.
Abstract: Background: The suspension of compulsory scheduling of some pediatric vaccines has been discussed for a long time by health authorities in Italy but the current decrease of vaccination rates is a m...
TL;DR: The chimeric yellow fever-dengue vaccine (CYD) that employs the yellow fever virus 17D strain as the replication backbone (Chimerivax-DEN; CYD-TDV) had an overall pooled protective efficacy of 65.6% but was substantially more effective against severe d Dengue and dengue hemorrhagic fever.
Abstract: Dengue has become a major global public health threat with almost half of the world's population living in at-risk areas. Vaccination would likely represent an effective strategy for the management of dengue disease in endemic regions, however to date there is only one licensed preventative vaccine for dengue infection. The development of a vaccine against dengue virus (DENV) has been hampered by an incomplete understanding of protective immune responses against DENV. The most clinically advanced dengue vaccine is the chimeric yellow fever-dengue vaccine (CYD) that employs the yellow fever virus 17D strain as the replication backbone (Chimerivax-DEN; CYD-TDV). This vaccine had an overall pooled protective efficacy of 65.6% but was substantially more effective against severe dengue and dengue hemorrhagic fever. Several other vaccine approaches have been developed including live attenuated chimeric dengue vaccines (DENVax and LAV Delta 30), DEN protein subunit V180 vaccine (DEN1-80E) and DENV DNA vaccines. These vaccines have been shown to be immunogenic in animals and also safe and immunogenic in humans. However, these vaccines are yet to progress to phase III trials to determine their protective efficacy against dengue. This review will summarize the details of vaccines that have progressed to clinical trials in humans.
TL;DR: An initial efficacy experiment in cynomolgus macaque nonhuman primates (NHPs) and a follow-on experiment in which an accelerated vaccination strategy consisting of 2 administrations, spaced 4 weeks apart demonstrate that the LASV DNA vaccine combined with dermal electroporation is a highly effective candidate for eventual use in humans.
Abstract: Lassa virus (LASV) is an ambisense RNA virus in the Arenaviridae family and is the etiological agent of Lassa fever, a severe hemorrhagic disease endemic to West and Central Africa.1,2 There are no...
TL;DR: In this article, the optimal immunogen dosage and immunization interval were optimized using a recombinant MERS-coronavirus (MERS-CoV) RBD fragment fused with Fc (S377-588-Fc) to evaluate the protective efficacy of RBD against MERS infection in human dipeptidyl peptidase 4 transgenic (hDPP4-Tg) mice.
Abstract: Middle East respiratory syndrome (MERS) continues to raise worldwide concerns due to its pandemic potential. Increased MERS cases and no licensed MERS vaccines highlight the need to develop safe and effective vaccines against MERS. We have previously demonstrated that a receptor-binding domain (RBD) fragment containing residues 377–588 of MERS-coronavirus (MERS-CoV) spike protein is a critical neutralizing domain and an important vaccine target. Nevertheless, its optimal immunogen dosage and immunization interval, key factors for human-used vaccines that induce protective immunity, have never been investigated. In this study, we optimized these criteria using a recombinant MERS-CoV RBD protein fused with Fc (S377–588-Fc) and utilized the optimal immunization schedule to evaluate the protective efficacy of RBD against MERS-CoV infection in human dipeptidyl peptidase 4 transgenic (hDPP4-Tg) mice. Compared with one dose and 2 doses at 1-, 2-, and 3-week intervals, a regimen of 2 doses of this protein...
TL;DR: The WHO recommended integration of universal mass vaccination (UMV) against hepatitis A virus (HAV) in national immunization schedules for children aged ≥ 1 year, if justified on the basis of acute H
Abstract: The WHO recommends integration of universal mass vaccination (UMV) against hepatitis A virus (HAV) in national immunization schedules for children aged ≥1 year, if justified on the basis of acute H
TL;DR: Preliminary Phase 1 data suggest that Ad26.ZEBOV/MVA-BN-Filo confers durable immunity for at least 240 d and is well-tolerated with a good safety profile, and may be suitable for prophylactic use in a regional or targeted population vaccination strategy, and could potentially aid prevention and control of future Ebola outbreaks.
Abstract: The consequences of the 2013–16 Ebola Zaire virus disease epidemic in West Africa were grave. The economies, healthcare systems and communities of Guinea, Sierra Leone and Liberia were devastated b...
TL;DR: The recombinant vesicular stomatitis virus-based vaccine (rVSV-EBOV) is the most promising candidate, which demonstrated a significant protection against EVD in phase III clinical trial, however, several concerns were still associated with the Ebola vaccine candidates.
Abstract: Ebola virus disease (EVD) has become a great threat to humans across the world in recent years. The 2014 Ebola epidemic in West Africa caused numerous deaths and attracted worldwide attentions. Since no specific drugs and treatments against EVD was available, vaccination was considered as the most promising and effective method of controlling this epidemic. So far, 7 vaccine candidates had been developed and evaluated through clinical trials. Among them, the recombinant vesicular stomatitis virus-based vaccine (rVSV-EBOV) is the most promising candidate, which demonstrated a significant protection against EVD in phase III clinical trial. However, several concerns were still associated with the Ebola vaccine candidates, including the safety profile in some particular populations, the immunization schedule for emergency vaccination, and the persistence of the protection. We retrospectively reviewed the current development of Ebola vaccines and discussed issues and challenges remaining to be investigated in the future.
TL;DR: Serotype data covering invasive pneumococcal disease (IPD) and non-IPD were extracted from articles published from March 2014 to March 2015, and Geographic variations in serotype distribution highlight the importance of monitoring evolving pneumococCal serotype prevalence after pneumococ CAL vaccine implementation.
Abstract: S. pneumoniae infection remains a serious public health concern despite the availability of vaccines covering up to 23 of more than 94 known serotypes. The purpose of the present study was to monit...
TL;DR: During the last decade the detailed knowledge of the allergen composition of hymenoptera venoms has substantially improved diagnosis and therapy of venom allergy, as well as on novel directions trying to improve therapy.
Abstract: Stings of hymenoptera can induce IgE-mediated hypersensitivity reactions in venom-allergic patients, ranging from local up to severe systemic reactions and even fatal anaphylaxis. Allergic patients' quality of life can be mainly improved by altering their immune response to tolerate the venoms by injecting increasing venom doses over years. This venom-specific immunotherapy is highly effective and well tolerated. However, component-resolved information about the venoms has increased in the last years. This knowledge is not only able to improve diagnostics as basis for an accurate therapy, but was additionally used to create tools which enable the analysis of therapeutic venom extracts on a molecular level. Therefore, during the last decade the detailed knowledge of the allergen composition of hymenoptera venoms has substantially improved diagnosis and therapy of venom allergy. This review focuses on state of the art diagnostic and therapeutic options as well as on novel directions trying to improve therapy.
TL;DR: The mechanism responsible for decreased immunization responses in obesity included leptin-induced systemic and B cell intrinsic inflammation, impaired T cell responses and lymphocyte division and proliferation, which might lead to an increased risk of HBV vaccine-escape mutations.
Abstract: Objective: Hepatitis B vaccine is regarded as the most effective method for the prevention of hepatitis B virus (HBV) infection. However, several factors such as age, body mass index and immunocompetent state have been reported to be associated with reduced immunization responses. The present commentary was aimed to discuss the influences of obesity on the immunogenicity of hepatitis B vaccines. Data sources: Available peer-reviewed literatures, practice guidelines, and statistics published on hepatitis B vaccine in obesity between 1973 and 2015. Conclusions: Obesity was significantly associated with non-response to hepatitis B vaccine immunization. The risk of nonresponsiveness of hepatitis B vaccine among obese people increased with BMI. Moreover, the obesity might lead to an increased risk of HBV vaccine-escape mutations. The mechanism responsible for decreased immunization responses in obesity included leptin-induced systemic and B cell intrinsic inflammation, impaired T cell responses and lym...