Declining Malaria Transmission Differentially Impacts the Maintenance of Humoral Immunity to Plasmodium falciparum in Children

Mugyenyi, Cleopatra K; Elliott, Salenna R.; Yap, Xi Zen; Feng, Gaoqian; Boeuf, Philippe; Fegan, Greg; Osier, Faith; Fowkes, Freya J. I.; Avril, Marion; Williams, Thomas N.; Marsh, Kevin; Beeson, James G.

doi:10.1093/infdis/jix370

Cited by 32 publications

(39 citation statements)

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“…A number of in vitro studies have explored how antibodies from immune individuals act against parasite replication in culture . Given that the inhibitory activity of antibodies is likely dependent on other host immune mechanisms present in vivo, these in vitro systems often add back immune effector mechanisms such as phagocytic cells or complement in order to better replicate the mechanisms available to the host in vivo . These studies have often emphasized a role for merozoite‐specific antibodies.…”

Section: Host Control Of Parasite Proliferationmentioning

confidence: 99%

“…[153][154][155][156][157][158] Given that the inhibitory activity of antibodies is likely dependent on other host immune mechanisms present in vivo, these in vitro systems often add back immune effector mechanisms such as phagocytic cells or complement in order to better replicate the mechanisms available to the host in vivo. [153][154][155][156][157] These studies have often emphasized a role for merozoite-specific antibodies. One study found that complement-dependent, antibody-mediated killing of merozoites was a major correlate of immunity in individuals.…”

Section: Determining Whether Immunity Acts Against the Merozoite Ormentioning

confidence: 99%

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Within‐host modeling of blood‐stage malaria

Khoury

Aogo

Randriafanomezantsoa‐Radohery

et al. 2018

Immunological Reviews

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Malaria infection continues to be a major health problem worldwide and drug resistance in the major human parasite species, Plasmodium falciparum, is increasing in South East Asia. Control measures including novel drugs and vaccines are in development, and contributions to the rational design and optimal usage of these interventions are urgently needed. Infection involves the complex interaction of parasite dynamics, host immunity, and drug effects. The long life cycle (48 hours in the common human species) and synchronized replication cycle of the parasite population present significant challenges to modeling the dynamics of Plasmodium infection. Coupled with these, variation in immune recognition and drug action at different life cycle stages leads to further complexity. We review the development and progress of "within-host" models of Plasmodium infection, and how these have been applied to understanding and interpreting human infection and animal models of infection.

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Section: Host Control Of Parasite Proliferationmentioning

confidence: 99%

Section: Determining Whether Immunity Acts Against the Merozoite Ormentioning

confidence: 99%

Within‐host modeling of blood‐stage malaria

Khoury

Aogo

Randriafanomezantsoa‐Radohery

et al. 2018

Immunological Reviews

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“…Phagocytosis results correlated with measurement of IgG3 antibody to the same antigens, and breadth of opsonizing antibody correlated with measures of merozoite phagocytosis, suggesting that opsonizing antibodies to a range of antigens are required for merozoite opsonic clearance, which is predominantly mediated by IgG3 antibodies. The half‐life of merozoite‐opsonizing antibodies appears relatively short, whereas that of complement‐fixing antibodies may be much longer …”

Section: Functional Antibody In Malariamentioning

confidence: 99%

Antibody effector functions in malaria and other parasitic diseases: a few needles and many haystacks

2020

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Many parasitic infections stimulate antibody responses in their mammalian hosts. The ability of these antibodies to protect against disease varies markedly. Research has revealed that functional properties of antibodies determine their role in protection against parasites. Investigations of antibodies against Plasmodium spp. have demonstrated a variety of functional activities, ranging from invasion inhibition and parasite growth inhibition to antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity. These activities have been demonstrated with a large variety of parasite molecules at multiple life cycle stages, highlighting the importance of functional antibody responses in malaria. Other parasitic infections have not yet been investigated in similar detail, but these mechanisms are likely to operate in nonmalarial parasitic infections as well. In this report, we review data on the role of functional antibody responses in protection from parasitic infections, highlighting discoveries in malaria, a parasite for which our knowledge base is the most advanced.

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“…Antibody levels and breadth of response to specific P. falciparum antigen targets generally diminish in the absence of re-infection, which is thought to contribute to loss of immunity (11)(12)(13)(14)(15)(16). However, there are differences in the rate of decay of antibodies to different antigens (17,18). Antibody responses to malaria are predominantly cytophilic (IgG1 and IgG3) and have been shown to mediate effector mechanisms that inhibit of parasite growth (19,20), promote opsonic phagocytosis (21) ) and complement fixation (22,23).…”

Section: Introductionmentioning

confidence: 99%

Impact of a rapid decline in malaria transmission on antimalarial IgG subclasses and avidity

Ssewanyana

Rek

Rodríguez

et al. 2020

Preprint

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Understanding how immunity to malaria is affected by declining transmission is important to aid vaccine design and understand disease resurgence. Both IgG subclasses and avidity of antigen-specific responses are important components of an effective immune response.Using a multiplex bead array assay, we measured the total IgG, IgG subclasses, and avidity profiles of responses to 18 P. falciparum blood stage antigens in samples from 160 Ugandans collected at 2 time points during high malaria transmission and 2 time points following a dramatic reduction in transmission.Results demonstrated that, for the antigens tested, (i) the rate of decay of total IgG following infection declined with age and was driven consistently by the decrease in IgG3 and occasionally the decrease in IgG1; (ii) the proportion of IgG3 relative to IgG1 in the absence of infection increased with age; (iii) the increase in avidity index (the strength of association between the antibody and antigen) following infection was largely due to a rapid loss of non-avid compared to avid total IgG; and (iv) both avid and non-avid total IgG in the absence of infection increased with age.Further studies are required to understand the functional differences between IgG1 and IgG3 in order to determine their contribution to the longevity of protective immunity to malaria. Measuring changes in antibody avidity may be a better approach of detecting affinity maturation compared to avidity index due to the differential expansion and contraction of high and low avidity total IgG.

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Declining Malaria Transmission Differentially Impacts the Maintenance of Humoral Immunity to Plasmodium falciparum in Children

Cited by 32 publications

References 50 publications

Within‐host modeling of blood‐stage malaria

Within‐host modeling of blood‐stage malaria

Antibody effector functions in malaria and other parasitic diseases: a few needles and many haystacks

Impact of a rapid decline in malaria transmission on antimalarial IgG subclasses and avidity

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