Showing papers in "Human Vaccines & Immunotherapeutics in 2019"
TL;DR: Cancer immunotherapy using PD-1/PD-L1 immune checkpoint blockade may require more studies, and this approach may be curative for patients with many types of cancer in the future.
Abstract: Programmed death-1 (PD-1) is a cell surface receptor that functions as a T cell checkpoint and plays a central role in regulating T cell exhaustion. Binding of PD-1 to its ligand, programmed death-ligand 1 (PD-L1), activates downstream signaling pathways and inhibits T cell activation. Moreover abnormally high PD-L1 expression on tumor cells and antigen-presenting cells in the tumor microenvironment mediates tumor immune escape, and the development of anti-PD-1/PD-L1 antibodies has recently become a hot topic in cancer immunotherapy. Here, we review the structure of PD-1 and PD-L1, the function of the PD-1/PD-L1 signaling pathway, the application of PD-1 or PD-L1 monoclonal antibodies and future directions for anti-PD-1/PD-L1 antibodies with combination therapies. Cancer immunotherapy using PD-1/PD-L1 immune checkpoint blockade may require more studies, and this approach may be curative for patients with many types of cancer in the future.
220 citations
TL;DR: An overview of Dengvaxia’s development is provided and what has been learned about product performance since its licensure is discussed.
Abstract: Dengue is the world's most prevalent and important arboviral disease. More than 50% of the world's population lives at daily risk of infection and it is estimated more than 95 million people a year seek medical care following infection. Severe disease can manifest as plasma leakage and potential for clinically significant hemorrhage, shock, and death. Treatment is supportive and there is currently no licensed anti-dengue virus prophylactic or therapeutic compound. A single dengue vaccine, Sanofi Pasteur's Dengvaxia®, has been licensed in 20 countries but uptake has been poor. A safety signal in dengue seronegative vaccine recipients stimulated an international re-look at the vaccine performance profile, new World Health Organization recommendations for use, and controversy in the Philippines involving the government, regulatory agencies, Sanofi Pasteur, clinicians responsible for testing and administering the vaccine, and the parents of vaccinated children. In this review, we provide an overview of Dengvaxia's® development and discuss what has been learned about product performance since its licensure.
175 citations
TL;DR: Comparative analyses indicated that confidence determinants differed by country and population groups, which supports the need to develop context-specific interventions to improve confidence in HPV vaccination and design community engagement strategies aiming to build public trust.
Abstract: Europe is increasingly described as the region in the world with the least confidence in vaccination, and particularly in the safety of vaccines. The aim of this systematic literature review was to gather and summarise all peer-reviewed and grey literature published about determinants of Human Papillomavirus (HPV) vaccine hesitancy in Europe. Ten thematic categories were identified across the 103 articles which were included in the review. Participants from European studies most commonly reported issues with the quantity and quality of information available about HPV vaccination; followed by concerns about potential side effects of the vaccine; and mistrust of health authorities, healthcare workers, and new vaccines. Comparative analyses indicated that confidence determinants differed by country and population groups. This evidence supports the need to develop context-specific interventions to improve confidence in HPV vaccination and design community engagement strategies aiming to build public trust.
147 citations
TL;DR: The literature overall is lacking in systematic and rigorous research examining the effects of social media on HPV related knowledge, attitudes, and behaviors and needs further examination as social media increasingly becomes a source of health information.
Abstract: This article summarizes the findings from a systematic literature review to examine how social media may impact HPV vaccine uptake and HPV and HPV vaccine related awareness, knowledge, and attitude...
125 citations
TL;DR: U uptake of the HPV vaccine remains modest, despite evidence that vaccine-type HPV prevalence is decreasing as a result of HPV vaccination, and geographic disparities in vaccination uptake across different US regions and by race/ethnicity may contribute to continuing disparities in HPV-related cancers.
Abstract: Human papillomavirus (HPV) is a common sexually transmitted infection which is the cause of several cancers, including cervical cancer, and genital warts. Although cervical cancer can be prevented through screening, this cancer persists in the US. More recently, HPV vaccination has the potential to decrease the burden of HPV-related disease among young HPV-unexposed adolescents. Several initiatives aimed to encourage HPV vaccination have been adopted. Unfortunately, uptake of the HPV vaccine remains modest, despite evidence that vaccine-type HPV prevalence is decreasing as a result of HPV vaccination. Further, geographic disparities in vaccination uptake across different US regions and by race/ethnicity may contribute to continuing disparities in HPV-related cancers. More data are needed to evaluate impact of HPV vaccination on HPV prevalence in smaller geographic areas. Further, more information is needed on the impact of individual vaccination programs and policy on population level vaccination and HPV prevalence.
124 citations
TL;DR: Genetic analyses have identified distinguished iNTS disease-causing strains that are particularly virulent in certain human host populations, and effective treatment strategies, including vaccination, are necessary.
Abstract: Invasive non-typhoidal Salmonella (iNTS) disease has emerged as a major public health concern. Yet, understanding of the global burden is incomplete, limited particularly by the breadth of blood cu...
102 citations
TL;DR: According to the assessed studies, the majority of the population seems to be in favour of compulsory vaccinations, although attitudes differed among studies, which could be an important starting point to further understand the issue of vaccine hesitancy and support the implementation of effective vaccination strategies.
Abstract: Currently, many countries are dealing with groups refusing available recommended vaccinations. Despite several studies having demonstrated the efficacy of mandatory vaccinations in ensuring herd im...
90 citations
TL;DR: The importance of routinely identifying gaps or breakdowns in public confidence in order to rebuild trust, before a pandemic threat, when societal and political cooperation with be key to an effective response is highlighted.
Abstract: In November 2017, it was announced that the new dengue vaccine ("Dengvaxia") had risks for those not previously exposed to dengue. While some countries proceeded with adjusting guidance accordingly, the Philippines reacted with outrage and political turmoil with naming and shaming of government officials involved in purchasing the vaccine, as well as scientists involved in the vaccine trials and assessment. The result was broken public trust around the dengue vaccine as well heightened anxiety around vaccines in general. The Vaccine Confidence ProjectTM measured the impact of this crisis, comparing confidence levels in 2015, before the incident, with levels in 2018. The findings reflect a dramatic drop in vaccine confidence from 93% "strongly agreeing" that vaccines are important in 2015 to 32% in 2018. There was a drop in confidence in those strongly agreeing that vaccines are safe from 82% in 2015 to only 21% in 2018; similarly confidence in the effectiveness of vaccines dropped from 82% in 2015 to only 22%. This article highlights the importance of routinely identifying gaps or breakdowns in public confidence in order to rebuild trust, before a pandemic threat, when societal and political cooperation with be key to an effective response.
85 citations
TL;DR: Global trends in MenW-IMD epidemiology over the last 5–10 years are described, with emphasis on the response of national/regional health authorities to increased MenW prevalence in impacted areas.
Abstract: Invasive meningococcal disease (IMD) is a serious disease that is fatal in 5–15% and disabling in 12–20% of cases. The dynamic and unpredictable epidemiology is a particular challenge of IMD preven...
77 citations
TL;DR: The accumulating evidence, available mostly from high and middle-income countries supporting a high impact of universal vaccination in reductions of the incidence of the disease and hospitalizations and its cost-effectiveness is summarized.
Abstract: Although varicella is usually a mild and self-limited disease, complications can occur. In 1998, the World Health Organization recommended varicella vaccination for countries where the disease has a significant public health burden. Nonetheless, concerns about a shift in the disease to older groups, an increase in herpes zoster in the elderly and cost-effectiveness led many countries to postpone universal varicella vaccine introduction. In this review, we summarize the accumulating evidence, available mostly from high and middle-income countries supporting a high impact of universal vaccination in reductions of the incidence of the disease and hospitalizations and its cost-effectiveness. We have also observed the effect of herd immunity and noted that there is no definitive and consistent association between vaccination and the increase in herpes zoster incidence in the elderly.
76 citations
TL;DR: This study contributes to the increasing body of safety data for IIV in pregnancy and reports a protective effect on PTB and LBW.
Abstract: Pregnant women are at increased risk of morbidity and mortality from influenza and are recognized as a priority group for influenza vaccination. Despite this, uptake is often poor and one reason cited for this is concerns about safety. The objective of this study was to perform a systematic review of the safety of inactivated influenza vaccination (IIV) in pregnancy. Studies were included if they were: (i) observational or experimental design; (ii) included a comparator group comprising of unvaccinated pregnant women; (iii) comprised of either seasonal IIV or monovalent H1N1 IIV (including adjuvanted vaccines); and (iv) addressed one of the following outcomes: preterm birth (PTB), small for gestational age (SGA), fetal death (including stillbirth or spontaneous abortion), low birth weight (LBW) or congenital abnormalities. Two reviewers screened abstracts and titles and selected full texts for retrieval. Crude odds ratios were calculated from reported event rates, using binomial standard errors. Adjusted odds ratios, hazard ratios and relative rates were extracted as reported in each paper. After removal of duplicates and full text eligibility assessment, 40 studies remained. The aOR for PTB was 0.87 (0.78-0.96), for LBW 0.82 (0.76-0.89), congenital abnormality 1.03 (0.99-1.07), SGA 0.99 (0.94-1.04) and stillbirth 0.84 (0.65-1.08). This study contributes to the increasing body of safety data for IIV in pregnancy and reports a protective effect on PTB and LBW.
TL;DR: In healthy adults ≥ 50 years of age, both new formulations of PCV15 displayed acceptable safety profiles and induced serotype-specific immune responses comparable to PCV13.
Abstract: Background: Pneumococcal disease remains a public health priority in adults. Safety and immunogenicity of 2 different formulations of 15-valent pneumococcal conjugate vaccine (PCV15) containing 13 ...
TL;DR: The incidence of oropharyngeal cancer related to infection with human papillomavirus (HPV) is rising, making it now the most common HPV-related malignancy in the United States as discussed by the authors.
Abstract: The incidence of oropharyngeal cancer (OPC) related to infection with human papillomavirus (HPV) is rising, making it now the most common HPV-related malignancy in the United States. These tumors p...
TL;DR: An overview of avian IgYs is provided and their potential therapeutic applications for the prevention and treatment of respiratory infections are described.
Abstract: Emergence of drug resistance among the causative organisms for respiratory tract infections represents a critical challenge to the global health care community. Further, although vaccination can prevent disease, vaccine development is impeded by several factors. Therefore, novel approaches to treat and manage respiratory infections are urgently needed. Passive immunization represents a possible alternative to meet this need. Immunoglobulin Y antibodies (IgYs) from the yolk of chicken eggs have previously been used against bacterial and viral infections in human and animals. Their advantages include lack of reaction with mammalian Fc receptors, low production cost, and ease of extraction. Compared to mammalian IgGs, they have higher target specificity and greater binding avidity. They also possess remarkable pathogen-neutralizing activity in the respiratory tract and lungs. In this review, we provide an overview of avian IgYs and describe their potential therapeutic applications for the prevention and treatment of respiratory infections.
TL;DR: Despite the potential deleterious effects of HPV, vaccine uptake remains suboptimal and the need for further research is needed to determine the best way to promote vaccine uptake.
Abstract: Human papillomavirus, or HPV, is the most common sexually transmitted disease in the United States. Despite the potential deleterious effects of HPV, vaccine uptake remains suboptimal. One potentia...
TL;DR: Dupilumab is a fully human monoclonal IgG4 antibody directed against the alpha subunit of the IL-4 receptor and prevents the signaling ofIL-4 and IL-13, two type 2 cytokines known to be important drivers of atopic diseases.
Abstract: Dupilumab is a fully human monoclonal IgG4 antibody directed against the alpha subunit of the IL-4 receptor and prevents the signaling of IL-4 and IL-13, two type 2 cytokines known to be important drivers of atopic diseases. In March of 2017, the United States Food and Drug Administration (FDA) approved dupilumab for the treatment of moderate-to-severe atopic dermatitis in adults that is uncontrolled with topical medications, becoming the first biologic agent approved to treat this chronic skin condition. In October of 2018, Dupilumab received approval by the FDA as an add-on maintenance therapy in patients with moderate-to-severe asthma aged 12 years or older with an eosinophilic phenotype or with oral corticosteroid-dependent asthma. This review summarizes the characteristics of dupilumab and the clinical research that has been published to date, including treatment efficacy and adverse events.
TL;DR: Evidence that serum IgG antibodies to Shigella LPS represent a good correlate of protection against shigellosis is reviewed, suggesting a threshold level of these antibodies associated with protection can promote the development of an efficacious vaccine for infants and young children.
Abstract: Shigella is a leading cause of diarrhea among children globally and of diarrheal deaths among children under 5 years of age in low- and middle-income countries. To date, no licensed Shigella vaccin...
TL;DR: An overview of the original and current strategies toward the development of a Shigella glycan-protein conjugate vaccine that would cover the most commonly detected strains and focus on promising alternatives.
Abstract: Shigella are gram-negative bacteria that cause severe diarrhea and dysentery, with a high level of antimicrobial resistance. Disease-induced protection against reinfection in Shigella-endemic areas provides convincing evidence on the feasibility of a vaccine and on the importance of Shigella lipopolysaccharides as targets of the host humoral protective immune response against disease. This article provides an overview of the original and current strategies toward the development of a Shigella glycan-protein conjugate vaccine that would cover the most commonly detected strains. Going beyond pioneering “lattice”-type polysaccharide-protein conjugates, progress, and challenges are addressed with focus on promising alternatives, which have reached phases I and II clinical trial. Glycoengineered bioconjugates and “sun”-type conjugates featuring well-defined synthetic carbohydrate antigens are discussed with insights on the molecular parameters governing the rational design of a cost-effective glycoconjugate vaccine efficacious in preventing diseases caused by Shigella in the most at risk populations, young children living in endemic areas.
TL;DR: In this review, insights gained from the clinical VSV-EBOV vaccine trials as well as from animal studies investigating vaccine candidates for Blueprint pathogens are discussed.
Abstract: The devastating Ebola virus (EBOV) outbreak in West Africa in 2013-2016 has flagged the need for the timely development of vaccines for high-threat pathogens. To be better prepared for new epidemics, the WHO has compiled a list of priority pathogens that are likely to cause future outbreaks and for which R&D efforts are, therefore, paramount (R&D Blueprint: https://www.who.int/blueprint/priority-diseases/en/ ). To this end, the detailed characterization of vaccine platforms is needed. The vesicular stomatitis virus (VSV) has been established as a robust vaccine vector backbone for infectious diseases for well over a decade. The recent clinical trials testing the vaccine candidate VSV-EBOV against EBOV disease now have added a substantial amount of clinical data and suggest VSV to be an ideal vaccine vector candidate for outbreak pathogens. In this review, we discuss insights gained from the clinical VSV-EBOV vaccine trials as well as from animal studies investigating vaccine candidates for Blueprint pathogens.
TL;DR: Mothers’ level of VH was strongly associated with their intention to vaccinate their infants, showing the potential detrimental impact of Vh on vaccine uptake rates and the importance of addressing this phenomenon.
Abstract: Background: Vaccine hesitancy (VH) is a growing problem. The first step in addressing VH is to have an understanding of who are the hesitant individuals and what are their specific concerns. The ai...
TL;DR: Five key myths about HPV vaccination are addressed – HPV vaccination is not effective at preventing cancer; Pap smears are sufficient to prevent cervical cancer; HPV vaccine is not safe; HPV vaccinations is not needed since most infections are naturally cleared by the immune system; 11–12 years of age is too young to vaccinate.
Abstract: Human papillomavirus (HPV) vaccine uptake consistently lags behind that of other adolescent vaccines. In 2017, uptake of a single HPV vaccine dose and HPV vaccine series completion was 66% and 49%,...
TL;DR: The current status of a human WNV vaccine is summarized and reasons for the lack of clinically advanced product candidates are discussed, and the problem of immunological cross-reactivity between flaviviruses is discussed and how it can be addressed during vaccine development.
Abstract: West Nile virus (WNV) is a widely spread human pathogenic arthropod-borne virus. It can lead to severe, sometimes fatal, neurological disease. Over the last two decades, several vaccine candidates for the protection of humans from WNV have been developed. Some technologies were transferred into clinical testing, but these approaches have not yet led to a licensed product. This review summarizes the current status of a human WNV vaccine and discusses reasons for the lack of clinically advanced product candidates. It also discusses the problem of immunological cross-reactivity between flaviviruses and how it can be addressed during vaccine development.
TL;DR: Current research highlights challenges of the modest effectiveness of the rotavirus vaccines in low- and lower-middle income countries, and considers alternative strategies to overcome them, including alternative immunization schedules and host factors that may inform us of new opportunities.
Abstract: Rotavirus vaccines have been introduced into over 95 countries globally and demonstrate substantial impact in reducing diarrheal mortality and diarrheal hospitalizations in young children. The vacc...
TL;DR: PCV15 is safe and induces IgG and OPA responses to all 15 serotypes in the vaccine and no significant differences in antibody responses were observed with increases in PnPs and/or Aluminum Phosphate Adjuvant.
Abstract: Background: Two new formulations of an investigational 15-valent pneumococcal conjugate vaccine (PCV15-A and PCV15-B) were developed using 2 different protein-polysaccharide conjugation processes a...
TL;DR: Many determinants are related to vaccine hesitancy and these determinants should be taken into account when health professionals engage with vaccine-hesitant individuals.
Abstract: Objectives: Vaccine hesitancy is a global phenomenon that needs to be measured and addressed. This study aimed to identify the determinants of vaccine hesitancy among a large regional population.Methods: A structured telephone survey was administered to a random digit sample in Quebec's Eastern Townships region. In addition to socioeconomic information, respondents were asked questions on several health topics such as knowledge and beliefs about immunization, medical consultations, health status, and life habits. Data were weighted according to age, sex, and territories. Statistically significant variables in the univariate analysis were introduced into a multivariate logistic regression model to determine independent factors for vaccine hesitancy (adjusted odds ratios [aOR] and 95% confidence intervals).Results: A total of 8,737 interviews were conducted (participation rate 48.3%). Among all respondents, 32.2% were vaccine-hesitant. Several beliefs were significantly associated with vaccine hesitancy: belief that children receive too many vaccines (aOR = 2.72; 2.32-3.18), belief that a healthy lifestyle can eliminate the need for vaccination (aOR = 2.48; 2.09-2.93), and belief that the use of alternative medicine practices can eliminate the need for vaccination (aOR = 1.39; 1.16-1.68). Other determinants associated with vaccine hesitancy were having consulted a massage therapist (aOR = 2.34; 1.46-3.75), not being vaccinated against influenza (aOR = 1.80; 1.49-2.16), having a low (<$30,000) (aOR = 1.58; 1.24-2.02) or moderate ($30,000-$79,000) (aOR = 1.37; 1.12-1.67) household income, distrust in public health authorities (aOR = 1.40; 1.21-1.63), perceived insufficient knowledge about immunization (aOR = 1.26; 1.04-1.51), and smoking (aOR = 1.22; 1.01-1.47).Conclusions: Many determinants are related to vaccine hesitancy. These determinants should be taken into account when health professionals engage with vaccine-hesitant individuals.
Kenya Medical Research Institute1, University of London2, Eduardo Mondlane University3, Muhimbili University of Health and Allied Sciences4, University of Basel5, Swiss Tropical and Public Health Institute6, Pwani University College7, University of Oxford8, National Institute for Medical Research9, Centers for Disease Control and Prevention10, University of North Carolina at Chapel Hill11, University of Tübingen12, University of Barcelona13, Kwame Nkrumah University of Science and Technology14
TL;DR: The observed meningitis and CM signals are considered likely chance findings, that – given their severity – warrant further evaluation in phase IV studies and WHO-led pilot implementation programs to establish the RTS,S/AS01 benefit-risk profile in real-life settings.
Abstract: A phase III, double-blind, randomized, controlled trial (NCT00866619) in sub-Saharan Africa showed RTS,S/AS01 vaccine efficacy against malaria. We now present in-depth safety results from this study. 8922 children (enrolled at 5-17 months) and 6537 infants (enrolled at 6-12 weeks) were 1:1:1-randomized to receive 4 doses of RTS,S/AS01 (R3R) or non-malaria control vaccine (C3C), or 3 RTS,S/AS01 doses plus control (R3C). Aggregate safety data were reviewed by a multi-functional team. Severe malaria with Blantyre Coma Score ≤2 (cerebral malaria [CM]) and gender-specific mortality were assessed post-hoc. Serious adverse event (SAE) and fatal SAE incidences throughout the study were 24.2%-28.4% and 1.5%-2.5%, respectively across groups; 0.0%-0.3% of participants reported vaccination-related SAEs. The incidence of febrile convulsions in children was higher during the first 2-3 days post-vaccination with RTS,S/AS01 than with control vaccine, consistent with the time window of post-vaccination febrile reactions in this study (mostly the day after vaccination). A statistically significant numerical imbalance was observed for meningitis cases in children (R3R: 11, R3C: 10, C3C: 1) but not in infants. CM cases were more frequent in RTS,S/AS01-vaccinated children (R3R: 19, R3C: 24, C3C: 10) but not in infants. All-cause mortality was higher in RTS,S/AS01-vaccinated versus control girls (2.4% vs 1.3%, all ages) in our setting with low overall mortality. The observed meningitis and CM signals are considered likely chance findings, that - given their severity - warrant further evaluation in phase IV studies and WHO-led pilot implementation programs to establish the RTS,S/AS01 benefit-risk profile in real-life settings.
TL;DR: Categorical definitions of vaccination timing vary widely, with benchmarks of delay varying from days to weeks to months, and use of a continuous measure of vaccine delay may be more informative and comparable.
Abstract: Background: Traditional measurements of vaccine coverage at specific ages can mask poor vaccine timeliness. However, optimal measurement of timing is unclear due to variations in countries' recommended vaccination schedules and lack of a commonly accepted standard for "timeliness". We conducted a systematic review of literature on vaccine timeliness and delay in low- and middle-income countries from 2007 to 2017.Methods: A search of articles published between January 1 2007 and December 31 2017, was performed in PubMed, EBSCOhost, and Embase.Results: 67 papers were included, of which 83% used a categorical measure of delay and 41% evaluated continuous delay. The most common age at assessment was 1 month, with earlier age benchmarks typically used with birth doses.Conclusions: Categorical definitions of vaccination timing vary widely, with benchmarks of delay varying from days to weeks to months. Use of a continuous measure of vaccine delay may be more informative and comparable.
TL;DR: The results show that antibiotics must be prescribed carefully in children with FS since the majority of cases are related to viral causes, and further vaccine candidates for potential respiratory pathogens, including RSV, might be helpful for the prevention of FS.
Abstract: Background: Febrile seizure is the most common childhood neurological disorder, is an important health problem with potential short- and long-term complications, also leading to economic burden and...
TL;DR: Despite weak health literacy is considered a concause of vaccine hesitancy, it is rarely taken into account when discussing about this subject and it is desirable that more instruments are validated and extensively used for assessing peoples’ vaccine literacy skills and defining interventions aimed at their improvement.
Abstract: Despite weak health literacy is considered a concause of vaccine hesitancy, it is rarely taken into account when discussing about this subject. The association between health literacy skills and va...
TL;DR: IIS could concretely represent a valid instrument to increase vaccine confidence, especially trust in both health-care workers and decision makers, and there are not enough trials aimed to evaluate the efficacy of IIS to counter VH.
Abstract: Immunization is one of the most important public health interventions to contrast infectious disease; however, many people nowadays refuse vaccination. Vaccine hesitancy (VH) is due to several factors that influence the complex decision-making process. Information technology tools might play an important role in vaccination programs. In particular, immunization information systems (IISs) have the potential to improve performance of vaccination programs and to increase vaccine uptake. This review aimed to present IIS functionalities in order to counter VH. In detail, we analyzed the automatic reminder/recall system, the interoperability of the system, the decision support system, the web page interface and the possibility to record adverse events following immunization. IIS could concretely represent a valid instrument to increase vaccine confidence, especially trust in both health-care workers and decision makers. There are not enough trials aimed to evaluate the efficacy of IIS to counter VH. Further researches might focalize on this aspect.