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Sun-Young Sunwoo, Michael Schotsaert, Igor Morozov, Anne Sally Davis, Yuhao Li, Jinhwa Lee, Chester McDowell, Philip Meade, Raffael Nachbagauer, Adolfo García-Sastre, Wenjun Ma, Florian Krammer, Juergen A Richt
The antigenically conserved hemagglutinin stalk region is a target for universal influenza virus vaccines since antibodies against it can provide broad protection against influenza viruses of different subtypes. We tested a universal influenza virus vaccination regimen based on sequential immunization with chimeric hemagglutinin (HA) containing viruses in a swine influenza virus pig model with maternal antibodies against pandemic H1N1. Vaccines were administered as live attenuated virus or inactivated influenza virus split vaccine (+/- Emulsigen adjuvant)...
September 14, 2018: Vaccines
Roel M van Harten, Esther van Woudenbergh, Albert van Dijk, Henk P Haagsman
Cathelicidins are host defense peptides with antimicrobial and immunomodulatory functions. These effector molecules of the innate immune system of many vertebrates are diverse in their amino acid sequence but share physicochemical characteristics like positive charge and amphipathicity. Besides being antimicrobial, cathelicidins have a wide variety in immunomodulatory functions, both boosting and inhibiting inflammation, directing chemotaxis, and effecting cell differentiation, primarily towards type 1 immune responses...
September 14, 2018: Vaccines
Raquel das Neves Almeida, Trina Racine, Kelly G Magalhães, Gary P Kobinger
Zika virus is an arbovirus that has rapidly spread within the Americas since 2014, presenting a variety of clinical manifestations and neurological complications resulting in congenital malformation, microcephaly, and possibly, in male infertility. These significant clinical manifestations have led investigators to develop several candidate vaccines specific to Zika virus. In this review we describe relevant targets for the development of vaccines specific for Zika virus, the development status of various vaccine candidates and their different platforms, as well as their clinical progression...
September 13, 2018: Vaccines
Eleanor Black, Robyn Richmond
Cervical cancer is a critical public health issue in sub-Saharan Africa (SSA), where it is the second leading cause of cancer among women and the leading cause of female cancer deaths. Incidence and mortality rates are substantially higher than in high-income countries with population-based screening programs, yet implementing screening programs in SSA has so far proven to be challenging due to financial, logistical, and sociocultural factors. Human Papillomavirus (HPV) vaccination is an effective approach for primary prevention of cervical cancer and presents an opportunity to reduce the burden from cervical cancer in SSA...
September 8, 2018: Vaccines
Rikhav P Gala, Rokon Uz Zaman, Martin J D'Souza, Susu M Zughaier
Neisseria gonorrhoeae is a strict human pathogen responsible for more than 100 million new sexually transmitted infections worldwide each year. Due to the global emergence of antibiotic resistance, the Center for Disease control (CDC) recently listed N. gonorrhoeae as an urgent threat to public health. No vaccine is available in spite of the huge disease burden and the possibility of untreatable gonorrhea. The aim of this study is to investigate the immunogenicity of a novel whole-cell-based inactivated gonococcal microparticle vaccine formulation loaded in dissolvable microneedles for transdermal administration...
September 4, 2018: Vaccines
Omotola Olasupo, Hong Xiao, Joshua D Brown
The relative burden of community-acquired pneumonia (CAP) in older adults (≥65 years old) compared to other serious diseases is important to prioritize preventive treatment. A retrospective analysis was conducted using the 2014 National Readmission Database to evaluate the length of stay, inpatient mortality, 30-day readmissions, and costs of CAP compared to diabetes mellitus (DM), myocardial infarction (MI), and stroke. 275,790 hospitalizations were analyzed and represented a national estimate of 616,300 hospitalizations, including 269,961 for CAP, 71,284 for DM, 126,946 for MI, and 148,109 for stroke...
August 31, 2018: Vaccines
Nicole M Bouvier
For centuries, the development of vaccines to prevent infectious disease was an empirical process. From smallpox variolation in Song dynasty China, through the polysaccharide capsule vaccines developed in the 1970s, vaccines were made either from the pathogen itself, treated in some way to render it attenuated or non-infectious, or from a closely related non-pathogenic strain. In recent decades, new scientific knowledge and technologies have enabled rational vaccine design in a way that was unimaginable before...
August 30, 2018: Vaccines
Lisa Kathleen Ryan, Jichuan Wu, Kyell Schwartz, Sunghan Yim, Gill Diamond
β-defensins are predicted to play an important role in innate immunity against bacterial infections in the airway. We previously observed that a type III-secretion product of Bordetella bronchiseptica inhibits the NF-κB-mediated induction of a β-defensin in airway epithelial cells in vitro. To confirm this in vivo and to examine the relative roles of other β-defensins in the airway, we infected wild-type C57BL/6 mice and mice with a deletion of the mBD-1 gene with B. bronchiseptica wild-type strain, RB50 and its mutant strain lacking the type III-secretion system, WD3...
August 28, 2018: Vaccines
Sandra Tuyaerts, Frédéric Amant
Endometrial stromal sarcomas are a subtype of uterine sarcomas that are characterized by recurrent chromosomal translocations, resulting in the expression of tumor-specific fusion proteins that contribute to their tumorigenicity. These characteristics make the translocation breakpoints promising targets for immunotherapeutic approaches. In this review, we first describe the current knowledge about the classification of endometrial stromal sarcomas, and their molecular and genetic characteristics. Next, we summarize the available data on the use of translocation breakpoints as immunotherapeutic targets...
August 25, 2018: Vaccines
Giselle M A Dutcher, Mehmet Asim Bilen
The field of genitourinary malignancies has been a showcase for therapeutic cancer vaccine success since the application of intravesicular Bacillus Calmette-Guerin (BCG) for bladder cancer in the 1970s and enjoyed a renaissance in 2010 with the US Food and Drug Administration (FDA) approval of sipuleucel-T for prostate cancer. Several vaccine strategies have emerged, such as autologous or allogeneic whole-tumor vaccines, DNA vaccines, use of viral vectors, and peptides as immunostimulatory adjuvants. Despite impressive early trials, vaccine monotherapy has achieved limited success in the clinical world; however, combinations of vaccine and immune checkpoint inhibition or vaccine and cytokine stimulation are expected to move the field forward...
August 12, 2018: Vaccines
Anusha Thadi, Marian Khalili, William F Morano, Scott D Richard, Steven C Katz, Wilbur B Bowne
Peritoneal metastasis (PM) is an advanced stage malignancy largely refractory to modern therapy. Intraperitoneal (IP) immunotherapy offers a novel approach for the control of regional disease of the peritoneal cavity by breaking immune tolerance. These strategies include heightening T-cell response and vaccine induction of anti-cancer memory against tumor-associated antigens. Early investigations with chimeric antigen receptor T cells (CAR-T cells), vaccine-based therapies, dendritic cells (DCs) in combination with pro-inflammatory cytokines and natural killer cells (NKs), adoptive cell transfer, and immune checkpoint inhibitors represent significant advances in the treatment of PM...
August 10, 2018: Vaccines
Zhiqiang Zheng, Subha Sankar Paul, Xiaobing Mo, Yu-Ren Adam Yuan, Yee-Joo Tan
Initial attempts to develop monoclonal antibodies as therapeutics to resolve influenza infections focused mainly on searching for antibodies with the potential to neutralise the virus in vitro with classical haemagglutination inhibition and microneutralisation assays. This led to the identification of many antibodies that bind to the head domain of haemagglutinin (HA), which generally have potent neutralisation capabilities that block viral entry or viral membrane fusion. However, this class of antibodies has a narrow breadth of protection in that they are usually strain-specific...
August 10, 2018: Vaccines
Angelika Terbuch, Juanita Lopez
Dramatic success in cancer immunotherapy has been achieved over the last decade with the introduction of checkpoint inhibitors, leading to response rates higher than with chemotherapy in certain cancer types. These responses are often restricted to cancers that have a high mutational burden and show pre-existing T-cell infiltrates. Despite extensive efforts, therapeutic vaccines have been mostly unsuccessful in the clinic. With the introduction of next generation sequencing, the identification of individual mutations is possible, enabling the production of personalized cancer vaccines...
August 9, 2018: Vaccines
Anthony Altieri, Hadeesha Piyadasa, Breann Recksiedler, Victor Spicer, Neeloffer Mookherjee
Antimicrobial peptides, also known as host defence peptides, are immunomodulatory molecules required to resolve infections. Antimicrobial peptides and proteins (APPs) are important in the control of infections in the lungs. Despite evidence that APPs exhibit a wide range of immune functions and modulate inflammation, the effect of inflammatory cytokines on the expression of APPs is not completely defined. In this study, we profiled the expression of 39 different APPs in human bronchial epithelial cells (HBEC) using Slow Off-rate Modified Aptamer (SOMAmer)-based protein array, in the presence and absence of three different inflammatory cytokines (IL-17, TNF and IFN-γ)...
August 7, 2018: Vaccines
Georgina Bowyer, Tommy Rampling, Jonathan Powlson, Richard Morter, Daniel Wright, Adrian V S Hill, Katie J Ewer
Immunogenicity of T cell-inducing vaccines, such as viral vectors or DNA vaccines and Bacillus Calmette-Guérin (BCG), are frequently assessed by cytokine-based approaches. While these are sensitive methods that have shown correlates of protection in various vaccine studies, they only identify a small proportion of the vaccine-specific T cell response. Responses to vaccination are likely to be heterogeneous, particularly when comparing prime and boost or assessing vaccine performance across diverse populations...
July 31, 2018: Vaccines
Anne M van der Does, Gimano D Amatngalim, Bart Keijser, Pieter S Hiemstra, Remi Villenave
The respiratory tract harbours a variety of microorganisms, collectively called the respiratory microbiota. Over the past few years, alterations in respiratory and gut microbiota composition have been associated with chronic inflammatory diseases of the lungs. How these changes influence disease development and progression is an active field of investigation. Identifying and understanding host-microbiota interactions and factors contributing to these interactions could promote the development of novel therapeutic strategies aimed at restoring host-microbiota homeostasis...
July 28, 2018: Vaccines
John C Flickinger, Ulrich Rodeck, Adam E Snook
Listeria monocytogenes , a Gram-positive facultative anaerobic bacterium, is becoming a popular vector for cancer immunotherapy. Indeed, multiple vaccines have been developed utilizing modified Listeria as a tool for generating immune responses against a variety of cancers. Moreover, over a dozen clinical trials testing Listeria cancer vaccines are currently underway, which will help to understand the utility of Listeria vaccines in cancer immunotherapy. This review aims to summarize current views on how Listeria -based vaccines induce potent antitumor immunity and the current state of Listeria -based cancer vaccines in clinical trials...
July 25, 2018: Vaccines
Raffael Nachbagauer, Florian Krammer, Randy A Albrecht
Influenza viruses cause severe diseases and mortality in humans on an annual basis. The current influenza virus vaccines can confer protection when they are well-matched with the circulating strains. However, due to constant changes of the virus surface glycoproteins, the vaccine efficacy can drop substantially in some seasons. In addition, the current seasonal influenza virus vaccines do not protect from avian influenza viruses of human pandemic potential. Novel influenza virus vaccines that aim to elicit antibodies against conserved epitopes like the hemagglutinin stalk could not only reduce the burden of drifted seasonal viruses but potentially also protect humans from infection with zoonotic and emerging pandemic influenza viruses...
July 25, 2018: Vaccines
Rory D de Vries, Sander Herfst, Mathilde Richard
Influenza A viruses can infect a wide range of hosts, creating opportunities for zoonotic transmission, i.e., transmission from animals to humans, and placing the human population at constant risk of potential pandemics. In the last hundred years, four influenza A virus pandemics have had a devastating effect, especially the 1918 influenza pandemic that took the lives of at least 40 million people. There is a constant risk that currently circulating avian influenza A viruses (e.g., H5N1, H7N9) will cause a new pandemic...
July 25, 2018: Vaccines
Yi-An Yang, Alexander Chong, Jeongmin Song
Salmonella enterica serovar Typhi ( S. Typhi) and S. Paratyphi, namely typhoidal Salmonellae, are the cause of (para) typhoid fever, which is a devastating systemic infectious disease in humans. In addition, the spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) S. Typhi in many low and middle-income countries poses a significant risk to human health. While currently available typhoid vaccines and therapeutics are efficacious, they have some limitations. One important limitation is the lack of controlling individuals who chronically carry S...
July 24, 2018: Vaccines
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