Malaria vaccine development: Lessons from the field

Todryk, Stephen; Bejon, Philip

doi:10.1002/eji.200939529

Cited by 5 publications

(3 citation statements)

References 42 publications

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“…The complex mechanisms by which malaria parasites interact with and modulate the immune system warrant continued investigation in such experimental challenge studies and in the field [37].…”

Section: Discussionmentioning

confidence: 99%

Multiple functions of human T cells generated by experimental malaria challenge

et al. 2009

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Protective immunity generated following malaria infection may be comprised of Ab or T cells against malaria Ag of different stages; however, the short-lived immunity that is observed suggests deficiency in immune memory or regulatory activity. In this study, cellular immune responses were investigated in individuals receiving Plasmodium falciparum sporozoite challenge by the natural (mosquito bite) route as part of a malaria vaccine efficacy trial. Parasitemia, monitored by blood film microscopy and PCR, was subsequently cleared with drugs. All individuals demonstrated stable IFN-c, IL-2 and IL-4 ex vivo ELISPOT effector responses against P. falciparum-infected RBC (iRBC) Ag, 28 and 90 days after challenge. However, infected RBC-specific central memory responses, as measured by IFN-c cultured ELISPOT, were low and unstable over time, despite CD4 1 T cells being highly proliferative by CFSE dilution, and showed an inverse relationship to parasite density. In support of the observation of poor memory, co-culture experiments showed reduced responses to common recall Ag, indicating malaria-specific regulatory activity. This activity could not be accounted for by the expression of IL-10, TGF-b, FOXP3 or CTLA-4, but proliferating T cells expressed high levels of CD95, indicating a pro-apoptotic phenotype. Lastly, there was an inverse relationship between FOXP3 expression, when measured 10 days after challenge, and ex vivo IFN-c measured more than 100 days later. This study shows that malaria infection elicits specific Th1 and Th2 effector cells, but concomitant weak central memory and regulatory activity, which may help to explain the short-lived immunity observed.

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Section: Discussionmentioning

confidence: 99%

Multiple functions of human T cells generated by experimental malaria challenge

et al. 2009

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“…The events that occur at the bite-site are still poorly understood and insights into processes such as the modulation of mammalian immune functions by arthropod saliva may provide new targets to combat diseases transmitted by arthropods. These diseases include mosquitoborne malaria (more than 1 million deaths/year) [5][6][7] mosquito-transmitted Dengue fever (more than 20 000 deaths/year and up to 3 billion people in more than 100 countries at risk), or tick-borne encephalitis ($12 000 reported Diseases, such as malaria, dengue, leishmaniasis and tick-borne encephalitis, affect a substantial percentage of the world's population and continue to result in significant morbidity and mortality. One common aspect of these diseases is that the pathogens that cause them are transmitted by the bite of an infected arthropod (e.g.…”

Section: Introductionmentioning

confidence: 99%

Immunological consequences of arthropod vector‐derived salivary factors

2011

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Diseases, such as malaria, dengue, leishmaniasis and tick‐borne encephalitis, affect a substantial percentage of the world's population and continue to result in significant morbidity and mortality. One common aspect of these diseases is that the pathogens that cause them are transmitted by the bite of an infected arthropod (e.g. mosquito, sand fly, tick). The pathogens are delivered into the skin of the mammalian host along with arthropod saliva, which contains a wide variety of bioactive molecules. These saliva components are capable of altering hemostasis and immune responses and may contribute to the ability of the pathogen to establish an infection. The biological and immunological events that occur during pathogen transmission are poorly understood but may hold the key to novel approaches to prevent transmission and/or infection. In May 2011, the National Institute of Allergy and Infectious Diseases (NIAID) of the US National Institutes of Health (NIH) in the Department of Health and Human Services hosted a workshop entitled Immunological Consequences of Vector‐Derived Factors which brought together experts in skin immunology, parasitology and vector biology to outline the gaps in our understanding of the process of pathogen transmission, to explore new approaches to control pathogen transmission, and to initiate and foster multidisciplinary collaborations among these investigators.

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“…Similarly, most models are chosen for 100% disease penetrance, to render experiments maximally “informative” and cost‐effective – but this again does not reflect the human situation and may place the “hurdle” of efficacy too low or too high. Todryk and Bejon 4 point out that critical information with regard to protective correlates of immunity to malaria have been and still are obtained from human field studies. Thus, the immune response of individuals with natural resistance against malaria should provide clues as to what vaccination must achieve.…”

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confidence: 99%

Animal models in infection and inflammation – chance and necessity

Radbruch

Isaacs

2009

Eur J Immunol

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In biomedical research, to understand pathogenesis and test innovative therapeutic strategies, animal models of human disease are a bare necessity. We cannot do without them, but could we do better with them? In this issue of the European Journal of Immunology a series of Viewpoints discusses the pros and cons of currently available animal models that address the clinical challenges of immunology in infection and inflammatory diseases.

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Malaria vaccine development: Lessons from the field

Cited by 5 publications

References 42 publications

Multiple functions of human T cells generated by experimental malaria challenge

Multiple functions of human T cells generated by experimental malaria challenge

Immunological consequences of arthropod vector‐derived salivary factors

Animal models in infection and inflammation – chance and necessity

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