Download or read book Towards a Multivalent Multistage Malaria Vaccine written by Elizabeth M. Parzych and published by . This book was released on 2018 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Progress towards the eradication of Plasmodium falciparum would be greatly enhanced by the development of a multivalent, multistage vaccine containing a transmission-blocking component. Unfortunately, several challenges have impeded the development of such a formulation, including 1) the recombinant production of complex targets in their proper native conformations, 2) the inherent, suboptimal immunogenicity of many protective candidates and 3) the induction and maintenance of protective responses against individual components in a multivalent context. Previous studies with PfMSP1, a protective blood-stage target that embodies these challenges, demonstrated that many of these issues could be addressed through the use of merozoite surface protein 8 (PfMSP8) as a carrier protein. We therefore applied this strategy to transmission-blocking vaccine candidate Pfs25. Antibodies directed against conformational epitopes within the four EGF-like domains of Pfs25 are capable of blocking sexual stage development in the mosquito vector. Using an E. coli expression system, we produced an rPfs25-PfMSP8 fusion protein (rPfs25/8(C[delta]S)) and an unfused, single rPfs25 antigen (rPfs25). rPfs25 was purified with a modest yield and required refolding procedures to obtain proper conformation. Alternatively, rPfs25/8(C[delta]S) was purified in higher yield without the need for refolding, via denaturation and renaturation, of the Pfs25 domain. Both antigens were immunogenic in rabbits, inducing IgG that bound native, parasite-associated Pfs25 and exhibited potent transmission-reducing activity. Comparative mouse studies were conducted to assess the effects of adjuvant selection (Alum vs. GLA-SE) and antigen dose (2.5 vs. 0.5 microgram) on the immunogenicity of these antigens. When formulated with Alum, a Th2-biasing adjuvant, both antigens elicited strong and comparable anti-Pfs25 titers irrespective of antigen dose. However, formulations with GLA-SE, a synthetic TLR4 agonist that supports a Th1-biased response, elicited divergent responses based on antigen. Immunization with rPfs25/8(C[delta]S) induced significantly higher anti-Pfs25 titers than immunization with rPfs25 at both doses, highlighting the requirement for genetic linkage of Pfs25 to the PfMSP8(C[delta]S) carrier in order to benefit from the adjuvant effect of GLA-SE. Of note, antigenic competition was observed when rPfs25 and rPfMSP8(C[delta]S) were co-administered as individual antigens, which was avoided through immunization with chimeric rPfs25/8(C[delta]S). Importantly, IgG induced by immunization with rPfs25/8(C[delta]S) demonstrated potent transmission-reducing activity, as measured by the in vivo standard membrane feeding assay (SMFA), irrespective of adjuvant. Based on these data, the chimeric rPfs25/8(C[delta]S) antigen was selected for further testing in a bivalent formulation with blood-stage vaccine candidate rPfMSP1/8(C[delta]S). Outbred mice that were co-immunized with rPfs25/8(C[delta]S) and rPfMSP1/8(C[delta]S) antigens produced strong antibody titers against both Pfs25 and PfMSP119 that were comparable to corresponding monovalent formulations, indicating the successful avoidance of antigenic competition. Consistent with previous results, immunization with rPfs25/8(C[delta]S) elicited comparable anti-Pfs25 antibody titers irrespective of adjuvant. However, immunization with rPfMSP1/8(C[delta]S) induced anti-PfMSP119 responses that were significantly higher when adjuvanted with GLA-SE relative to Alum-based formulations. These data are promising as we continue to assess and optimize additional blood-stage antigens (PfMSP2 and PfRh5), moving towards the ultimate goal of producing a highly efficacious, multivalent vaccine to reduce both blood stage-mediated clinical disease and transmission of P. falciparum parasites.
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 Battling Malaria written by Institute of Medicine and published by National Academies Press. This book was released on 2006-08-26 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 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 Federal Register written by and published by . This book was released on 1999-05-14 with total page 970 pages. Available in PDF, EPUB and Kindle. Book excerpt:
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 Immunity to Malaria and Vaccine Strategies written by Kevin N. Couper and published by Frontiers Media SA. This book was released on 2019-10-10 with total page 487 pages. Available in PDF, EPUB and Kindle. Book excerpt: Malaria, caused by infection with protozoan parasites belonging to the genus Plasmodium, is a highly prevalent and lethal infectious disease, responsible for 435,000 deaths in 2017. Optimism that malaria was gradually being controlled and eliminated has been tempered by recent evidence that malaria control measures are beginning to stall and that Plasmodium parasites are developing resistance to front-line anti-malarial drugs. An important milestone has been the recent development of a malaria vaccine (Mosquirix) for use in humans, the very first against a parasitic infection. Unfortunately, this vaccine has modest and short-lived efficacy, with vaccinated individuals possibly being at increased risk of severe malarial disease when protection wanes. Thus, to define new ways to combat malaria, there remains an urgent requirement to identify the immune mechanisms that promote resistance to malarial disease and to understand why these so often fail. The review and primary research articles in this Research Topic illustrate the breadth of research performed worldwide aimed to understand the biology of the Plasmodium parasite, the roles of the various cell types that act within the immune response against the parasite, and the parasitological and immunological basis of severe malarial disease. The articles in section 1 exemplify the different vaccination strategies being developed and tested by the research community in the fight against malaria. The articles in section 2 review important overarching aspects of malaria immunology and the use of models to study human malaria. The articles in section 3 describe the ways through which the Plasmodium parasite is initially recognised by the immune system during infection, how the parasite can directly impact this critical event to restrict anti-Plasmodial immunity, and resolve the roles of key innate cell populations, such as dendritic cells, in coordinating malarial immunity. The articles in sections 4-6 outline the roles T and B cell populations play during malaria, highlighting the activation, diversification and regulation of the crucial cell types during malaria, and discuss some of the reasons adaptive immunity to malaria is often considered so poor compared with other diseases. The articles in section 7 provide up to date information on the pathogenesis of cerebral malaria, bridging our understanding of the syndrome in humans with information learned from animal models. Overall, the articles in this research, many of which are published by leaders in the malaria field, emphasize the imagination and technical advances being employed by researchers against malaria. We acknowledge the initiation and support of this Research Topic by the International Union of Immunological Societies (IUIS). We hereby state publicly that the IUIS has had no editorial input in articles included in this Research Topic, thus ensuring that all aspects of this Research Topic are evaluated objectively, unbiased by any specific policy or opinion of the IUIS.
Download or read book Vaccines written by Peter Perlman and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 553 pages. Available in PDF, EPUB and Kindle. Book excerpt: The immune system is the only organ system in the body besides the central nervous systems endowed with memory. Both types of memories are specific and long-lasting, sometimes life long. This memory capacity of the immune system provides the basis for the most cost-efficient of all medical interventions, successful vaccinations against many common infectious diseases. Such a success requires the isolation of the infectious agent or toxic substance, methods to grow and/or purify the relevant antigen and change it into something innocuous whilst maintaining its immunogenicity. Whereas the early vaccines could only use the enhanced resistance against infectious disease as a measure of vaccine efficacy, most modern vaccines rely upon standardized laboratory tests accepted to parallel the in vivo protective capacity to confirm the quality and potency of the respective vaccine. We are presently experiencing an explosion in the development of new and/or improved vaccines. This is largely due to a parallel rapid expansion in our knowledge of the immune system and of the detailed molecular structure and function of microorganisms. Using this knowledge it is now possible to compose vaccines of new types where only certain molecules (or parts of molecules) derived from a pathogen are included, excluding other potentially harmful ones. Whereas earlier attenuated live vaccines were created by em pirical means such vaccines can now be created by molecularly defined inter ventions in the genome of the microorganism.
Download or read book Army Science And Technology Master Plan 2001 Volume 1 January 2001 written by and published by . This book was released on 2001 with total page 428 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Genetic Engineering of Crop Plants for Food and Health Security written by Siddharth Tiwari and published by Springer Nature. This book was released on with total page 517 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Army Science and Technology Master Plan written by United States. Department of the Army and published by . This book was released on 2001 with total page 428 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Proceedings of the National Academy of Sciences of the United States of America written by National Academy of Sciences (U.S.) and published by . This book was released on 1999 with total page 1472 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Artificial DNA written by Yury E. Khudyakov and published by CRC Press. This book was released on 2002-09-25 with total page 435 pages. Available in PDF, EPUB and Kindle. Book excerpt: Combining elements of biochemistry, molecular biology, and immunology, artificial DNA can be employed in a number of scientific disciplines. Some of the varied applications include site-specific mutagenesis, hybridization, amplification, protein engineering, anti-sense technology, DNA vaccines, protein vaccines, recombinant antibodies, screening fo
Download or read book Tropical Diseases written by Sangkot Marzuki and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 390 pages. Available in PDF, EPUB and Kindle. Book excerpt: Tropical Diseases: From Molecule to Bedside covers a wide range of topics that reflect perspectives of northern and southern hemispheres. Fittingly, it defines tropical diseases in a broader-than-usual manner. The book discusses traditional tropical medicine topics of infectious diseases and nutritional deficiencies. These diseases are common in the tropics, although some are associated more with poverty than with tropical living conditions. It also deals with genetic diseases and genomic issues that are truly associated with living in the tropics, e.g. the thalassemias. The book begins with several papers describing the vast human genetic diversity of Southeast Asia and its relationship to several genetic disorders. These papers illustrate the future direction of genomic activities in relation to disease susceptibility and resistance. The next sections deal with malaria and four specific viral and bacterial diseases of the tropics: hepatitis B and C, tuberculosis, and leprosy, followed by a section on general bacterial infection. Two papers on nutrition complete the volume.
Download or read book Immunization Safety Review written by Institute of Medicine and published by National Academies Press. This book was released on 2002-07-02 with total page 304 pages. Available in PDF, EPUB and Kindle. Book excerpt: By two years of age, healthy infants in the United States can receive up to 20 vaccinations to protect against 11 diseases. Although most people know that vaccines effectively protect against serious infectious diseases, approximately one-quarter of parents in a recent survey believe that infants get more vaccines than are good for them, and that too many immunizations could overwhelm an infant's immune system. The Immunization Safety Review Committee reviewed the evidence regarding the hypothesis that multiple immunizations increase the risk for immune dysfunction. Specifically, the committee looked at evidence of potential biological mechanisms and at epidemiological evidence for or against causality related to risk for infections, the autoimmune disease type 1 diabetes, and allergic disorders.
Download or read book Army Science And Technology Master Plan 2001 Volume 2 Annexes January 2001 written by and published by . This book was released on 2001 with total page 388 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Proceedings written by Indian National Science Academy and published by . This book was released on 2002 with total page 620 pages. Available in PDF, EPUB and Kindle. Book excerpt:
