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      Escaping the enemy’s bullets: an update on how malaria parasites evade host immune response

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          Abstract

          Malaria continues to cause untold hardship to inhabitants of malaria-endemic regions, causing significant morbidity and mortality that severely impact global health and the economy. Considering the complex life cycle of malaria parasites (MPs) and malaria biology, continued research efforts are ongoing to improve our understanding of the pathogenesis of the diseases. Female Anopheles mosquito injects MPs into its hosts during a blood meal, and MPs invade the host skin and the hepatocytes without causing any serious symptoms. Symptomatic infections occur only during the erythrocytic stage. In most cases, the host’s innate immunity (for malaria-naïve individuals) and adaptive immunity (for pre-exposed individuals) mount severe attacks and destroy most MPs. It is increasingly understood that MPs have developed several mechanisms to escape from the host’s immune destruction. This review presents recent knowledge on how the host’s immune system destroys invading MPs as well as MPs survival or host immune evasion mechanisms. On the invasion of host cells, MPs release molecules that bind to cell surface receptors to reprogram the host in a way to lose the capacity to destroy them. MPs also hide from the host immune cells by inducing the clustering of both infected and uninfected erythrocytes (rosettes), as well as inducing endothelial activation. We hope this review will inspire more research to provide a complete understanding of malaria biology and promote interventions to eradicate the notorious disease.

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          A guide to vaccinology: from basic principles to new developments

          Immunization is a cornerstone of public health policy and is demonstrably highly cost-effective when used to protect child health. Although it could be argued that immunology has not thus far contributed much to vaccine development, in that most of the vaccines we use today were developed and tested empirically, it is clear that there are major challenges ahead to develop new vaccines for difficult-to-target pathogens, for which we urgently need a better understanding of protective immunity. Moreover, recognition of the huge potential and challenges for vaccines to control disease outbreaks and protect the older population, together with the availability of an array of new technologies, make it the perfect time for immunologists to be involved in designing the next generation of powerful immunogens. This Review provides an introductory overview of vaccines, immunization and related issues and thereby aims to inform a broad scientific audience about the underlying immunological concepts.
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            Acquired immunity to malaria.

            Naturally acquired immunity to falciparum malaria protects millions of people routinely exposed to Plasmodium falciparum infection from severe disease and death. There is no clear concept about how this protection works. There is no general agreement about the rate of onset of acquired immunity or what constitutes the key determinants of protection; much less is there a consensus regarding the mechanism(s) of protection. This review summarizes what is understood about naturally acquired and experimentally induced immunity against malaria with the help of evolving insights provided by biotechnology and places these insights in the context of historical, clinical, and epidemiological observations. We advocate that naturally acquired immunity should be appreciated as being virtually 100% effective against severe disease and death among heavily exposed adults. Even the immunity that occurs in exposed infants may exceed 90% effectiveness. The induction of an adult-like immune status among high-risk infants in sub-Saharan Africa would greatly diminish disease and death caused by P. falciparum. The mechanism of naturally acquired immunity that occurs among adults living in areas of hyper- to holoendemicity should be understood with a view toward duplicating such protection in infants and young children in areas of endemicity.
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              Malaria: Biology and Disease.

              Malaria has been a major global health problem of humans through history and is a leading cause of death and disease across many tropical and subtropical countries. Over the last fifteen years renewed efforts at control have reduced the prevalence of malaria by over half, raising the prospect that elimination and perhaps eradication may be a long-term possibility. Achievement of this goal requires the development of new tools including novel antimalarial drugs and more efficacious vaccines as well as an increased understanding of the disease and biology of the parasite. This has catalyzed a major effort resulting in development and regulatory approval of the first vaccine against malaria (RTS,S/AS01) as well as identification of novel drug targets and antimalarial compounds, some of which are in human clinical trials.
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                Author and article information

                Contributors
                timothy.ezeorba@unn.edu.ng
                Journal
                Parasitol Res
                Parasitol Res
                Parasitology Research
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0932-0113
                1432-1955
                23 May 2023
                23 May 2023
                2023
                : 122
                : 8
                : 1715-1731
                Affiliations
                [1 ]GRID grid.10757.34, ISNI 0000 0001 2108 8257, Department of Microbiology, Faculty of Biological Sciences, , University of Nigeria, ; Enugu State, 410001 Nigeria
                [2 ]GRID grid.39158.36, ISNI 0000 0001 2173 7691, Division of Soft Matter, , Hokkaido University, ; Sapporo, 060-0810 Japan
                [3 ]GRID grid.10757.34, ISNI 0000 0001 2108 8257, Department of Biochemistry, Faculty of Biological Sciences, , University of Nigeria, ; Enugu State, 410001 Nigeria
                [4 ]GRID grid.10757.34, ISNI 0000 0001 2108 8257, Department of Genetics and Biotechnology, Faculty of Biological Sciences, , University of Nigeria, ; Enugu State, 410001 Nigeria
                [5 ]GRID grid.6572.6, ISNI 0000 0004 1936 7486, Department of Molecular Biotechnology, School of Biosciences, , University of Birmingham Edgbaston, ; Birmingham, B15 2TT UK
                Author notes

                Handling Editor: Una Ryan

                Article
                7868
                10.1007/s00436-023-07868-6
                10348937
                37219610
                5c927b77-0f10-485a-b580-fdbebaadbca5
                © The Author(s) 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 25 March 2023
                : 8 May 2023
                Categories
                Review
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2023

                Parasitology
                malaria,host immune response,evasion of host immunity,rosetting,plasmodium infection
                Parasitology
                malaria, host immune response, evasion of host immunity, rosetting, plasmodium infection

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