Longevity of the Immune Response and Memory to Blood-Stage Malaria Infection

Achtman, Ariel H.; Bull, Peter C.; Stephens, Robin; Langhorne, Jean

doi:10.1007/3-540-29967-x_3

Cited by 74 publications

(75 citation statements)

References 171 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is important to note that despite preventing ECM the anti-CD25 mAb combined vaccine strategy did not result in ultimate control of parasite growth and mice eventually succumbed to hyperparasitemia and anemia. We believe that this failure to control parasite growth after protection from ECM could be attributed to either inappropriate downregulation of malaria-specific CD4 + T cell responses, as previously described in this model (70,71), or a failure to generate an effective antiparasitic Ab response, as reported in several different experimental malaria models (11,72). These two possibilities are not mutually exclusive, and we are currently developing ways to improve our malaria vaccine formulation to enhance both aspects of our vaccine-induced immunity.…”

Section: Discussionmentioning

confidence: 52%

Immune-Mediated Mechanisms of Parasite Tissue Sequestration during Experimental Cerebral Malaria

Amante

Haque

Stanley

et al. 2010

The Journal of Immunology

156

180

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 52%

Immune-Mediated Mechanisms of Parasite Tissue Sequestration during Experimental Cerebral Malaria

Amante

Haque

Stanley

et al. 2010

The Journal of Immunology

156

180

View full text Add to dashboard Cite

show abstract

“…Indeed, in one particular study volunteers were immunized with low doses of Plasmodium-infected RBC (iRBC), and they produced T-cell IFN-g responses against blood-stage Ag that were associated with protection from challenge in the absence of Ab responses [7]. A frequently described observation is the apparently short-lived immunity generated after exposure to the parasite [8,9], which may be a result of depressed cellular immunity [10,11]. We have recently shown that recipients of experimental malaria vaccines in Kenya had decreased T-cell responses against the vaccine Ag when parasitemic at the time of vaccination [12].…”

Section: Introductionmentioning

confidence: 99%

Multiple functions of human T cells generated by experimental malaria challenge

et al. 2009

View full text Add to dashboard Cite

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.

show abstract

“…Thirdly, we have not explicitly modelled the effects of parasite genetic diversity and have thus, strictly speaking, treated infections as monoclonal. However, the widely accepted hypothesis that immune development is regulated by antigenic variation and cumulative exposure to inoculations of differing parasite strains [20,22,26,32,36] is analogous to our definition of immunity levels in terms of cumulative exposure with finite memory. Our model is therefore consistent with theories in which immunity is strain-specific whilst integrating other aspects of acquired immunity development supported by cross-sectional data and current immunological understanding.…”

Section: Discussionmentioning

confidence: 98%

Determination of the processes driving the acquisition of immunity to malaria using a mathematical transmission model

Filipe¹,

Riley²,

Drakeley³

et al. 2005

PLoS Comput Biol

View full text Add to dashboard Cite

Acquisition of partially protective immunity is a dominant feature of the epidemiology of malaria among exposed individuals. The processes that determine the acquisition of immunity to clinical disease and to asymptomatic carriage of malaria parasites are poorly understood, in part because of a lack of validated immunological markers of protection. Using mathematical models, we seek to better understand the processes that determine observed epidemiological patterns. We have developed an age-structured mathematical model of malaria transmission in which acquired immunity can act in three ways (''immunity functions''): reducing the probability of clinical disease, speeding the clearance of parasites, and increasing tolerance to subpatent infections. Each immunity function was allowed to vary in efficacy depending on both age and malaria transmission intensity. The results were compared to age patterns of parasite prevalence and clinical disease in endemic settings in northeastern Tanzania and The Gambia. Two types of immune function were required to reproduce the epidemiological age-prevalence curves seen in the empirical data; a form of clinical immunity that reduces susceptibility to clinical disease and develops with age and exposure (with half-life of the order of five years or more) and a form of anti-parasite immunity which results in more rapid clearance of parasitaemia, is acquired later in life and is longer lasting (half-life of .20 y). The development of anti-parasite immunity better reproduced observed epidemiological patterns if it was dominated by age-dependent physiological processes rather than by the magnitude of exposure (provided some exposure occurs). Tolerance to subpatent infections was not required to explain the empirical data. The model comprising immunity to clinical disease which develops early in life and is exposure-dependent, and anti-parasite immunity which develops later in life and is not dependent on the magnitude of exposure, appears to best reproduce the pattern of parasite prevalence and clinical disease by age in different malaria transmission settings. Understanding the effector mechanisms underlying these two immune functions will assist in the design of transmission-reducing interventions against malaria.

show abstract

Longevity of the Immune Response and Memory to Blood-Stage Malaria Infection

Cited by 74 publications

References 171 publications

Immune-Mediated Mechanisms of Parasite Tissue Sequestration during Experimental Cerebral Malaria

Immune-Mediated Mechanisms of Parasite Tissue Sequestration during Experimental Cerebral Malaria

Multiple functions of human T cells generated by experimental malaria challenge

Determination of the processes driving the acquisition of immunity to malaria using a mathematical transmission model

Contact Info

Product

Resources

About