Download or read book Preclinical Assessment of the Immunogenicity Durability and Efficacy Induced by Pre erythrocytic Vaccines Against Plasmodium Falciparum Malaria written by Hayley Klingenberg and published by . This book was released on 2023 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Malaria is an ongoing global health problem caused by Plasmodium parasites that results in the death of over half a million people each year. The majority of these deaths occur in children under five years old who lack memory immune responses to protect them from infection. A major step towards prevention of malaria is through vaccination with RTS,S, the only WHO approved vaccines to date. RTS,S contains a portion of the central repeat region and the C-terminus of the pre-erythrocytic stage Plasmodium falciparum circumsporozoite protein (PfCSP). CSP is essential for sporozoite entry into hepatocytes making it a strong vaccine target. Naturally acquired and vaccine-induced immune responses towards this protein have been associated with protection against infection. Pre-erythrocytic stage vaccines aim to clear sporozoites and prevent progression to the blood-stage of the infection, which is the cause of disease pathology. RTS,S makes use of a Hepatitis B surface antigen (HbsAg) carrier to help improve immunogenicity and vaccine delivery. Extensive clinical trials have found that immunization with RTS,S results in low vaccine efficacy that wanes over time. This study aimed to improve upon the specificity, efficacy, and durability of RTS,S through the inclusion of the N-terminal region of PfCSP and the use of a Plasmodium-specific carrier protein. This project extended prior work that assessed the magnitude, specificity, and avidity of the antibody response induced by immunization with four novel PfCSP-based vaccine constructs adjuvanted with glucopyranosyl lipid adjuvant (GLA-SE). Three out of four of our constructs are fused to the blood stage protein, merozoite surface protein 8 (PfMSP8), which has been shown to improve the production and immunogenicity of other Plasmodium protein-based vaccines. The focus of the current thesis project was to assess the T cell responses, epitope recognition, antibody persistence and protective efficacy in vivo of our novel recombinant PfCSP-based vaccines. We demonstrate that inclusion of the N-terminal domain of PfCSP broadens the antibody response to include recognition of known linear B cell epitopes. Vaccination with our constructs drives robust antibody responses to conformational C-terminal epitopes as well as high anti-PfCSP antibody titers that remain durable for at least 6 months. Our constructs induce strong T cell responses, measured by the production of IFN-[gamma] by stimulated splenocytes, but this response shifts in specificity away from PfCSP towards PfMSP8 when mice were immunized with our fused chimeric constructs. However, this did not impact overall efficacy, as immunization with our chimeric PfCSP/8 construct resulted in significant protection against blood stage infection in mice when challenged intravenously with transgenic P. yoelii sporozoites that express PfCSP. These data demonstrate improvements over RTS,S and warrant further testing of the chimeric PfCSP/8 construct for use in a multivalent vaccine for P. falciparum malaria.
Download or read book Malaria written by Institute of Medicine and published by National Academies Press. This book was released on 1991-02-01 with total page 312 pages. Available in PDF, EPUB and Kindle. Book excerpt: Malaria is making a dramatic comeback in the world. The disease is the foremost health challenge in Africa south of the Sahara, and people traveling to malarious areas are at increased risk of malaria-related sickness and death. This book examines the prospects for bringing malaria under control, with specific recommendations for U.S. policy, directions for research and program funding, and appropriate roles for federal and international agencies and the medical and public health communities. The volume reports on the current status of malaria research, prevention, and control efforts worldwide. The authors present study results and commentary on the: Nature, clinical manifestations, diagnosis, and epidemiology of malaria. Biology of the malaria parasite and its vector. Prospects for developing malaria vaccines and improved treatments. Economic, social, and behavioral factors in malaria control.
Download or read book World Malaria Report 2018 written by World Health Organization and published by World Health Organization. This book was released on 2019-02-12 with total page 210 pages. Available in PDF, EPUB and Kindle. Book excerpt: This year s report shows that after an unprecedented period of success in global malaria control progress has stalled. Data from 2015?2017 highlight that no significant progress in reducing global malaria cases was made in this period. There were an estimated 219 million cases and 435 000 related deaths in 2017. The World malaria report 2018 draws on data from 90 countries and areas with ongoing malaria transmission. The information is supplemented by data from national household surveys and databases held by other organizations.
Download or read book Battling Malaria written by Institute of Medicine and published by National Academies Press. This book was released on 2006-07-26 with total page 144 pages. Available in PDF, EPUB and Kindle. Book excerpt: Malaria is an infectious disease common to several parts of the world, including Africa, northern South America, and Asia. During their service in the military, U.S. active members may be sent to any part of the world, including parts of the world where Malaria is an issue. In Liberia in 2003, for example, there was a 28 percent attack rate in Marines who spent a short time ashore, and half of the 80 Marines affected needed to be evacuated to Germany. This was not only costly to the U.S. military but dangerous as well. To fight against this disease, there exists a Malaria Vaccine program in the U.S. military. However, there exists a variety of potential vaccine targets for the most severe and important form of malaria; malaria from the species Plasmodium falciparum. Issues also arise with the fact that there are three possible stages to create vaccines against-preerythrocytic, blood, or transmission. The Department of Defense (DoD), through the commanding general of the U.S. Army Medical Research and Materiel Command (USAMRMC), requested that the Institute of Medicine (IOM) conduct a programmatic review of the military Plasmodium falciparum malaria vaccine research and development program. There was to be a focus on vaccine against the preerythrocytic and blood stages. The IOM formed a committee of 11 experts with collective expertise in malaria vaccine research, parasite immunology, malarial biology, clinical trials and regulatory affairs, industrial and public-sector vaccine development, biologic products research and development (vaccinology), military research and development programs, tropical medicine, and public health. The committee focused different tasks including determining whether the DoD malaria vaccine research and development program is scientifically sound and able to achieve the vaccine program objectives within specified timelines, recommending how to overcome significant, identified barriers, and identifying major strategic goals and timelines based on the material received and presentations made by the DoD's program representatives. Battling Malaria: Strengthening the U.S. Military Malaria Vaccine Program presents the committee's findings, current malaria vaccines, and recommendations for the development of the U.S. Military vaccine research.
Download or read book Malaria vaccines preferred product characteristics and clinical development considerations written by World Health Organization and published by World Health Organization. This book was released on 2022-09-30 with total page 77 pages. Available in PDF, EPUB and Kindle. Book excerpt: Preferred product characteristics” (PPCs) are key tools to incentivize and guide the development of urgently needed health products. The PPCs published here aim to articulate the public health need, preferred characteristics, and clinical development considerations for new malaria vaccines. WHO PPCs were initially conceived in 2012-2013 as a class of research-oriented normative guidance documents. The first edition of the WHO PPCs for malaria vaccines (WHO/IVB/14.09), published in 2014, was the first-in-class of these documents. The document published here is an update to the 2014 edition. Since the first malaria vaccine PPCs were published in 2014, major milestones in malaria vaccine R&D have been achieved. In 2021, RTS,S/AS01 became the first malaria vaccine to be recommended by WHO for use in moderate- to high-transmission settings in sub-Saharan Africa. However, a healthy market of vaccines will be needed to meet the global demand. A continued focus on developing new and improved vaccines will be vital in our efforts to reduce global malaria burden and to achieve elimination and eradication. This includes malaria vaccines to prevent blood-stage infection, reduce morbidity and mortality, and/or reduce community-level transmission.
Download or read book Analysis of Immune Responses Related to Protection Against P Falciparum Pre erythrocytic Stages written by Blanca-liliana Perlaza and published by . This book was released on 2000 with total page 428 pages. Available in PDF, EPUB and Kindle. Book excerpt: Malaria is one of the most evasive infectious diseases in the world. The development of a vaccine against the human malaria parasite Plasrnodium falciparum requires first, the identification of the parasitic antigens involved in protection, and second, the use of appropriate animal models to study protective immune mechanisms and to optimize immunization protocols intended to induce them. A subset of P. falciparum preerythrocytic antigens (LSA l, LSA3, SALSA and STARP) have been identified and characterized. Among them, LSA3 displayed promising antigenic, immunogenic and protective efficacy in différent animal models. The current thesis describes the immune responses induced by these antigens, particularly the immunogenicity and protective potential of LSA3 in mice and Aotus monkeys. Aotus lemurinus griseirnembra is a small New World monkey. We confirmed that the species A./.griseimembra is susceptible to infection by P. falciparum sporozoites and we were able to maintain the parasite by cyclical passages through Aotns and mosquitoes. When Aotus lemurinus were immunized with either, a mixture of lipopeptides from 4 P. falciparum preerythrocytic antigens or LSA3 recombinant proteins, the monkeys were able to induce high cellular and humoral immune responses, indicating that it is a suitable animal model for evaluating immunogenicity of pre-erythrocytic antigens. Finally, for the first time we report evidence of protection against challenge with P. falciparum sporozoites in Aotus monkeys.Taking advantage of the recent advances in peptide synthesis, we used 17 Long Synthetic Peptides (LSP) covering all the LSA3 protein to confirm the antigenicity of LSA3 antigen in individuals highly exposed to natural P. falciparum infections. In addition, these LSP were found to be strongly immunogenic in mice, eliciting T-helper, CTL responses and specific antibody production. On the other hands, LSA3-DNA-based immunization in mice induced high immune responses against different regions of the molecule and preferentially generated responses Th 1-type. Moreover, this immunization protocol was able to induce protection against the challenge with P. yoelii sporozoites. These findings confirm previous results about the vaccine potential of LSA3 and allow to validate Aolus monkeys as model for preerythrocytic malaria vaccines research. They open the way to a great number of future studies on P. falciparum pre-erythrocytic stages.
Download or read book Malaria Immunology written by Peter Perlmann and published by Karger Medical and Scientific Publishers. This book was released on 2002-01-01 with total page 422 pages. Available in PDF, EPUB and Kindle. Book excerpt: Despite extensive efforts to control it, malaria is still one of the most devastating infectious diseases worldwide. This book, now in its second edition, provides a broad and up-to-date overview of the rapidly expanding field of malaria immunology and its importance in the control of this disease. The first section deals with the malaria parasite and its interactions with both the vertebrate host and the mosquitoes which transmit the disease. In the second part, the mechanisms of immunity and their regulation by environmental and genetic factors are discussed. Finally, this volume contains several chapters on malaria vaccine development, describing the application of the most recent vaccine technologies as well as ongoing and planned vaccine trials. Authored by well-recognized experts, this volume not only demonstrates the rapid progress being made in the search for vaccines against malaria, but also broadens our understanding of immunity to infection in general. It is therefore highly recommended reading for all scientists and professionals in the fields of immunology, infection and vaccine development.
Download or read book World malaria report 2017 written by World Health Organization and published by World Health Organization. This book was released on 2018-02-12 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The World Malaria Report 2017 presents a comprehensive state of play in global progress in the fight against malaria up to the end of 2016. It tracks progress in investments in malaria programs and research, malaria prevention, diagnosis and treatment, surveillance, trends in malaria disease burden, malaria elimination, and threats in tackling malaria and safeguarding the investments made. The report draws on data from 91 countries and areas with ongoing malaria transmission. The information is supplemented by data from national household surveys and databases held by other organizations. This year's report shows that after an unprecedented period of success in global malaria control, progress has stalled. In 2016, there were an estimated 216 million cases of malaria, an increase of about 5 million cases over 2015. Deaths reached 445,000, a similar number to the previous year.
Download or read book Towards Malaria Elimination written by Sylvie Manguin and published by BoD – Books on Demand. This book was released on 2018-07-18 with total page 454 pages. Available in PDF, EPUB and Kindle. Book excerpt: Towards Malaria Elimination - A Leap Forward was started to mark the occasion for renewed commitment to end malaria transmission for good (the WHO's call for "Malaria Free World" by 2030). This book is dedicated for the benefit of researchers, scientists, program and policy managers, students and anyone interested in malaria and other mosquito-borne diseases with the goal of sharing recent information on success stories, innovative control approaches and challenges in different regions of the world. Some main issues that emerged included multidrug-resistant malaria and pandemic risk, vaccines, cross-border malaria, asymptomatic parasite reservoir, the threat of Plasmodium vivax and Plasmodium knowlesi, insecticide resistance in Anopheles vectors and outdoor malaria transmission. This book is one little step forward to bring together in 17 chapters the experiences of malaria-expert researchers from five continents to present updated information on disease epidemiology and control at the national/regional level, highlighting the constraints, challenges, accomplishments and prospects of malaria elimination.
Download or read book Chimpanzees in Biomedical and Behavioral Research written by National Research Council and published by National Academies Press. This book was released on 2011-12-05 with total page 200 pages. Available in PDF, EPUB and Kindle. Book excerpt: For many years, experiments using chimpanzees have been instrumental in advancing scientific knowledge and have led to new medicines to prevent life-threatening and debilitating diseases. However, recent advances in alternate research tools have rendered chimpanzees largely unnecessary as research subjects. The Institute of Medicine, in collaboration with the National Research Council, conducted an in-depth analysis of the scientific necessity for chimpanzees in NIH-funded biomedical and behavioral research. The committee concludes that while the chimpanzee has been a valuable animal model in the past, most current biomedical research use of chimpanzees is not necessary, though noted that it is impossible to predict whether research on emerging or new diseases may necessitate chimpanzees in the future.
Download or read book Design Production and Evaluation of a Plasmodium Falciparum Merozoite Surface Protein 2 based Vaccine for Inclusion in a Multivalent Formulation Targeting Multiple Parasite Stages written by Jacqueline Schneider Eacret and published by . This book was released on 2019 with total page 229 pages. Available in PDF, EPUB and Kindle. Book excerpt: Development of a highly efficacious vaccine will be necessary for malaria elimination. Studies in Plasmodium falciparum endemic areas indicate that naturally acquired antibody responses to MSP2 are associated with resistance to malaria, making PfMSP2 an attractive vaccine candidate. To overcome challenges encountered with subunit malaria vaccines, we established that the use of highly immunogenic rPfMSP8 as a carrier protein for vaccine candidates rPfMSP119 and rPfs25 facilitated production, minimized antigenic competition and enhanced induction of functional antibodies. Here, we exploited the benefits of our rPfMSP8 fusion partner to optimize a rPfMSP2-based subunit vaccine. A synthetic PfMSP2 (3D7) codon harmonized gene was used to produce unfused rPfMSP2 or chimeric rPfMSP2/8 in E. coli. Purified, rPfMSP2 formed amyloid-like fibrils in vitro, however rPfMSP2/8 did not. Immunization of rabbits and mice with both rPfMSP2 antigens elicited high titer anti-PfMSP2 antibodies that recognized the major allelic variants of native PfMSP2. Competition assays revealed differences in antibody specificities induced by the two rPfMSP2-based vaccines, with evidence of epitope masking by rPfMSP2-associated fibrils. Immunogenicity studies in mice demonstrated that formulation of rPfMSP2 vaccines with GLA-SE, a synthetic TLR4 agonist, elicited cytophilic IgG isotypes and production of Th1-associated cytokines. T cell responses were specific for epitopes within PfMSP2 and PfMSP8 domains. The rPfMSP2/8 + GLA-SE formulation induced significantly higher antibody titers with superior durability and capacity to opsonize P. falciparum merozoites for phagocytosis. Immunization with a trivalent vaccine including PfMSP2/8, PfMSP1/8 and Pfs25/8 induced high levels of antigen-specific antibody, with no evidence of antigenic competition. These results are highly encouraging for the addition of rPfMSP2/8 as a component of an efficacious, multivalent, multistage malaria vaccine.
Download or read book Assessment of Long Term Health Effects of Antimalarial Drugs When Used for Prophylaxis written by National Academies of Sciences, Engineering, and Medicine and published by National Academies Press. This book was released on 2020-04-24 with total page 427 pages. Available in PDF, EPUB and Kindle. Book excerpt: Among the many who serve in the United States Armed Forces and who are deployed to distant locations around the world, myriad health threats are encountered. In addition to those associated with the disruption of their home life and potential for combat, they may face distinctive disease threats that are specific to the locations to which they are deployed. U.S. forces have been deployed many times over the years to areas in which malaria is endemic, including in parts of Afghanistan and Iraq. Department of Defense (DoD) policy requires that antimalarial drugs be issued and regimens adhered to for deployments to malaria-endemic areas. Policies directing which should be used as first and as second-line agents have evolved over time based on new data regarding adverse events or precautions for specific underlying health conditions, areas of deployment, and other operational factors At the request of the Veterans Administration, Assessment of Long-Term Health Effects of Antimalarial Drugs When Used for Prophylaxis assesses the scientific evidence regarding the potential for long-term health effects resulting from the use of antimalarial drugs that were approved by FDA or used by U.S. service members for malaria prophylaxis, with a focus on mefloquine, tafenoquine, and other antimalarial drugs that have been used by DoD in the past 25 years. This report offers conclusions based on available evidence regarding associations of persistent or latent adverse events.
Download or read book Immunopotentiators in Modern Vaccines written by Virgil Schijns and published by Elsevier. This book was released on 2005-12-19 with total page 396 pages. Available in PDF, EPUB and Kindle. Book excerpt: Immunopotentiators in Modern Vaccines provides an in-depth insight and overview of a number of most promising immunopotentiators in modern vaccines. In contrast to existing books on the subject it provides recent data on the critical mechanisms governing the activity of vaccine adjuvants and delivery systems. Knowledge of immunological pathways and scenarios of the cells and molecules involved is described and depicted in comprehensive illustrations. Contributions from leading international authorities in the field Well-illustrated, informative figures present the interactions between immunopotentiators and the host immune system Each chapter lists advantages and potential hurdles for achieving a practical application for the specific immunopentiator
Download or read book Human Challenge Studies in Endemic Settings written by Euzebiusz Jamrozik and published by Springer Nature. This book was released on 2020 with total page 145 pages. Available in PDF, EPUB and Kindle. Book excerpt: This open access book provides an extensive review of ethical and regulatory issues related to human infection challenge studies, with a particular focus on the expansion of this type of research into endemic settings and/or low- and middle-income countries (LMICs). Human challenge studies (HCS) involve the intentional infection of research participants, and this type of research is rapidly increasing in frequency worldwide. HCS are widely considered to be an especially promising approach to vaccine development, including for pathogens endemic to LMICs. However, challenge studies are sometimes controversial and raise complex ethical issues, some of which are especially salient in endemic and/or LMIC settings. Informed by qualitative interviews with experts in infectious diseases and bioethics, this book highlights areas of ethical consensus and controversy concerning this kind of research. As the first volume to focus on ethical issues associated with human challenge studies, it sets the agenda for further work in this important area of global health research; contributes to current debates in research ethics; and aims to inform regulatory policy and research practice. Insofar as it focuses on HCS in (endemic) settings where diseases are present and/or widespread, much of the analysis provided here is directly relevant to HCS involving pandemic diseases including COVID19.
Download or read book Vaccines written by Ciro A. de Quadros and published by Pan American Health Org. This book was released on 2004 with total page 410 pages. Available in PDF, EPUB and Kindle. Book excerpt: This publication contains a number of papers which consider the public health role of vaccines in improving the health of the world's populations, and looks at the challenges of using immunisation to combat emerging and re-emerging diseases. Issues discussed include the innovative use of vaccines against diseases such as meningococcal infection in Africa, Haemophilus influenza type b, varicella, and hepatitis, efforts to develop a new generation of vaccines against cholera and typhoid, shigella and Helicobacter pylori, as well as developments in the quest for vaccines against tuberculosis, HIV/AIDS, dengue, malaria, and hookworm. It also deals with the use of vaccines to fight bioterrorism attacks; regulatory and safety issues; financing issues, impact of health sector reform and the sustainability of immunisation programmes.
Download or read book Malaria written by Maria M. Mota and published by Springer. This book was released on 2017-01-12 with total page 275 pages. Available in PDF, EPUB and Kindle. Book excerpt: Currently, malaria kills more than 300,000 people per year, making it a top priority of world leaders and international organizations, who are working towards implementing and coordinating efforts to eradicate this disease. An effective malaria vaccine is recognized as the key element that will decide between success and failure in this fight. At present, despite intensive research efforts, such a vaccine is not yet available for use. However, there are a number of advanced candidate vaccines with high chances of success in the short term. Malaria: Immune Response to Infection and Vaccination provides a comprehensive view on the immune response to malaria and to the different vaccines under development. The book offers the following: - Contributions by top research leaders in the field, - Comparisons of the immune responses to both malaria infection and malaria vaccines, which are traditionally treated separately, - Coverage of the immune responses to the different stages of malaria, which are frequently treated as separate fields of research.
Download or read book Gene Vaccines written by Josef Thalhamer and published by Springer Science & Business Media. This book was released on 2011-08-31 with total page 332 pages. Available in PDF, EPUB and Kindle. Book excerpt: The induction of antigen-specific immune responses after in vivo transfection with expression plasmids has triggered a revolution of vaccine research. After a first hype, evoked by the fascinating options of this method, clinical studies did not reach the ambitious aims and a phase of disillusion ensued. It became obvious that Gene vaccines displayed a weaker immunogenicity in humans than had been observed in the mouse models. Meanwhile these hurdles have been overcome and gene vaccines undergo a renaissance. The present book gives an update of the “world of naked gene vaccines”, namely DNA and RNA vaccines. Its content ranges from general mechanisms, inherent immunostimulatory properties and the vast potential to modulate immune responses, to recent successful clinical studies and approved veterinary gene vaccines. Beyond the state-of-the-art of genetic immunization, the reader will be stimulated with a chapter addressing “burning questions”.
