Transient cross-reactive immune responses can orchestrate antigenic variation in malaria

@article{Recker2004TransientCI,
  title={Transient cross-reactive immune responses can orchestrate antigenic variation in malaria},
  author={Mario Recker and Sean Nee and Peter Bull and Samson Kinyanjui and Kevin Marsh and Chris I Newbold and Sunetra Gupta},
  journal={Nature},
  year={2004},
  volume={429},
  pages={555-558}
}
The malaria parasite Plasmodium falciparum has evolved to prolong its duration of infection by antigenic variation of a major immune target on the surface of the infected red blood cell. This immune evasion strategy depends on the sequential, rather than simultaneous, appearance of immunologically distinct variants. Although the molecular mechanisms by which a single organism switches between variants are known in part, it remains unclear how an entire population of parasites within the host… 

Cross-Reactive Immune Responses as Primary Drivers of Malaria Chronicity

A model to examine the role of cross-reactivity in generating infection dynamics that are comparable to those of experimental infections demonstrates that cross- reactive immune responses play a primary role in generating the dynamics observed in experimentally untreated infections and in lengthening the period of infection.

How do antigenically varying pathogens avoid cross-reactive responses to invariant antigens?

This work uses simple mathematical models that explicitly consider the dynamic interplay between the replicating pathogen, immune responses to different antigens and immune exhaustion to explore how pathogens can escape the responses to both variable and invariant (conserved) antIGens.

Antigenic Variation in Plasmodium falciparum Malaria Involves a Highly Structured Switching Pattern

A genome-wide approach is used to explore a non-random, highly structured switch pathway where an initially dominant transcript switches via a set of switch-intermediates either to a new dominant transcript, or back to the original, demonstrating a crucial role for structured switching during the early phases of infections.

Within-host dynamics of antigenic variation.

  • S. FrankA. Barbour
  • Biology
    Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases
  • 2006

Multi-scale immune selection and the maintenance of structured antigenic diversity in the malaria parasite Plasmodium falciparum

It is shown that treating diversity as a dynamic property, which emerges from the underlying infection and transmission processes, has a major effect on the relationship between the parasite’s transmission potential and disease prevalence, with important implications for monitoring control efforts.

Conflicting immune responses can prolong the length of infection in Plasmodium falciparum malaria

The behaviour of a reduced system under conditions of perfect synchrony between variants is analysed to demonstrate that these features of this system can be attributed to the antagonism between cross-reactive and variant-specific responses.

Critical Interplay between Parasite Differentiation, Host Immunity, and Antigenic Variation in Trypanosome Infections

A mechanistic framework for modeling within‐host infection dynamics of the sleeping sickness parasite, the African trypanosome, shows that the degree of synchronization in stochastic variant emergence determines the relative dominance of general over specific control within a single peak.

Immune Selection and Within-Host Competition Can Structure the Repertoire of Variant Surface Antigens in Plasmodium falciparum - A Mathematical Model

A mathematical model of the evolutionary mechanisms shaping VSA organization and expression patterns is formulated, which reproduces immunological trends observed in field data, and predicts an evolutionary stable balance between inter-clonally conserved dominance blocks that are highly competitive within-host and diverse blocks that is favoured by immune selection at the population level.

Plasmodium falciparum variant erythrocyte surface antigens: a pilot study of antibody acquisition in recurrent natural infections

This pilot study validates the utility of recurrent natural malaria infections as a functional readout for examining the incremental acquisition of immunity to malaria.
...

References

SHOWING 1-10 OF 38 REFERENCES

Antigenic variation and the within-host dynamics of parasites.

It is argued that increasing antigenic diversity leads to a switch from variant-specific to cross-reactive immune responses, and this work uses mathematical models to investigate the dynamical interaction between an antigenically varying parasite and the host's immune system.

Evolutionary pattern of intra-host pathogen antigenic drift: effect of cross-reactivity in immune response.

  • Y. HaraguchiA. Sasaki
  • Biology
    Philosophical transactions of the Royal Society of London. Series B, Biological sciences
  • 1997
This paper theoretically study the pattern of intra-host micro-evolution of pathogen antigen variants under the antigen specific immune response, assuming that the antigen types of the pathogen can be indexed in one-dimensional space and that a mutation can produce a new antigen variant that is one step distant from the parental type.

Parasite antigens on the infected red cell surface are targets for naturally acquired immunity to malaria

It is shown that the PfEMPI variants expressed during episodes of clinical malaria were less likely to be recognized by the corresponding child's own preexisting antibody response than by that of children of the same age from the same community.

A model for the sequential dominance of antigenic variants in African trypanosome infections

  • S. Frank
  • Biology
    Proceedings of the Royal Society of London. Series B: Biological Sciences
  • 1999
A mathematical model of parasitaemia and host immunity is used to show that small variations in the rate at which each type switches to other types can explain the observations, and shows that randomly chosen switch rates do not provide sufficiently ordered parasitaemias to match the observations.

Nine-Year Longitudinal Study of Antibodies to Variant Antigens on the Surface of Plasmodium falciparum-Infected Erythrocytes

This study provides evidence that malaria is associated with a short-lived, variant-specific antibody response to PfEMP1-like antigens exposed on the surface of parasitized erythrocytes, and suggests that the antigenic repertoires of variant antigen expressed by different parasite isolates show considerable overlapping under Sahelian conditions of low-intensity, seasonal, and unstable malaria transmission.

Antigenic oscillations and shifting immunodominance in HIV-1 infections

A new mathematical model is developed that deals with the interaction between CTL and multiple epitopes of a genetically variable pathogen, and it is shown that the nonlinear competition among CTL responses against different epitopes can explain immunodominance.

The surface variant antigens of Plasmodium falciparum contain cross-reactive epitopes

The demonstration of cross-reactive epitopes on the PE surface provides further credence for development of effective vaccines against the variant antigen on the surface of P. falciparum-infected erythrocytes.

Plasmodium falciparum Infection Elicits Both Variant-Specific and Cross-Reactive Antibodies against Variant Surface Antigens

Mixed-agglutination assays confirm the presence of both variant-specific and partially cross-reactive antibodies in convalescent-phase sera from Rourkela and adultSera from San Dulakudar, suggesting that they have antibodies with wide recognition of diverse PfEMP-1.

Antigenic variation in trypanosomes: a computer analysis of variant order

The tendency towards a reproducible order of variants was strong, although in several of the studies the number of experimental animals was so low that no conclusions could be drawn, and the random generation-selection hypothesis can be proven or disproven.

Plasmodium falciparum infections are associated with agglutinating antibodies to parasite-infected erythrocyte surface antigens among healthy Kenyan children.

It is suggested that parasitization status may be an important consideration in longitudinal assessments of the protective role of some anti-parasite immune responses and data from a prospective study of VSA antibodies in a group of children who subsequently had severe malaria are supported.