Parasite Antigens and Antigenic Variation

Parasite antigens are the molecules a host immune system recognizes during parasitic infection, and antigenic variation is the strategy by which many parasites systematically change those molecules to stay ahead of immunity. Antigenic variation is one of the most important reasons parasitic infections persist and recur and why vaccines against parasites such as the malaria parasite and African trypanosomes have been so difficult to develop.

Definition

Antigenic variation is the process by which a parasite systematically changes the antigens it exposes to the host immune system, typically by switching expression among a repertoire of surface antigen genes, so that immune responses raised against earlier variants no longer recognize the parasite.

Scope

This topic covers the nature of parasite antigens, especially variant surface antigens, and the genetic and molecular mechanisms by which protozoan parasites switch among them to evade antibody responses. It draws comparisons with other pathogens that use similar strategies and treats antigenic variation as a reference concept in parasite immunology, not as clinical guidance.

Core questions

• What molecules act as the principal antigens recognized during parasitic infection?
• How do parasites switch among variant surface antigens?
• Why does antigenic variation allow chronic and relapsing infection?
• How does antigenic variation complicate vaccine development?

Key concepts

• Parasite surface antigens
• Variant surface antigens
• Variant surface glycoprotein (VSG) of trypanosomes
• PfEMP1 and var gene switching in Plasmodium falciparum
• Gene repertoires and mutually exclusive expression
• Sequential waves of parasitaemia
• Antigenic diversity and vaccine escape

Mechanisms

Many parasites carry large families of genes encoding variant surface antigens and express only one (or a few) at a time, switching among them so that antibodies effective against one variant fail against the next. African trypanosomes change their variant surface glycoprotein (VSG) coat, and Plasmodium falciparum switches expression among var genes encoding the PfEMP1 surface protein, producing successive antigenic forms during infection (Deitsch, 2009; Crompton, 2014). These switches arise through largely epigenetic, mutually exclusive gene-expression control and gene-conversion mechanisms, and comparable strategies are used by some bacterial, fungal, and other protozoan pathogens, indicating convergent solutions to the problem of antibody-mediated immunity (Deitsch, 2009). Antigenic variation interacts with broader immune evasion and immunomodulation, contributing to the persistence of infection (Maizels, 2003).

Clinical relevance

Antigenic variation explains the recurring waves of parasitaemia in trypanosomiasis, the difficulty of acquiring sterilizing immunity to malaria, and a central obstacle to vaccines against antigenically variable parasites. The entry describes these mechanisms for reference and education and is not a basis for diagnosing or treating individuals.

History

The molecular basis of antigenic variation was first worked out in African trypanosomes, where switching of the VSG coat was shown to drive successive waves of parasitaemia. Later work on Plasmodium falciparum var genes and PfEMP1 extended the concept to malaria, and comparative analysis revealed that diverse pathogens converge on similar antigenic-variation strategies (Deitsch, 2009; Crompton, 2014).

Debates

Antigenic diversity as a barrier to parasite vaccines

Because antigenically variable parasites present a moving and diverse target, it is debated whether protective vaccines must target conserved antigens or invariant stages rather than the variable surface antigens that dominate natural immune responses.

Key figures

• Kirk Deitsch
• Peter Crompton
• Rick Maizels

Seminal works

• deitsch-2009
• crompton-2014

Frequently asked questions

What is antigenic variation in parasites?

It is the ability of a parasite to change the surface antigens the immune system targets, switching among many variant genes so that antibodies made against one form no longer recognize the parasite, allowing it to persist.

Why does antigenic variation make malaria and sleeping sickness hard to cure with immunity?

Parasites like Plasmodium falciparum and African trypanosomes continually switch their surface antigens, producing successive waves of infection that stay ahead of the antibody response, which is also a major reason effective vaccines have been difficult to develop.