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Exploring Plasmodium falciparum Var Gene Expression to Assess Host Selection Pressure on Parasites During Infancy
Cheryl A Kivisi1,2,3, Michelle Muthui1, Martin Hunt4
1KEMRI Wellcome Trust Research Programme, Kilifi, Kenya.
Insights
Maternal antibodies offer protection against severe malaria in infants by influencing parasite gene expression. As maternal antibodies wane, Plasmodium falciparum var gene expression changes, indicating immune pressure.
Area of Science:
- Immunology
- Infectious Diseases
- Genetics
Background:
- Children under 5 in sub-Saharan Africa face the highest severe malaria burden due to lack of immunity.
- Antibodies to Plasmodium falciparum infected erythrocytes (IE) are crucial for immunity.
- Maternal antibodies acquired trans-placentally may protect infants under 6 months, but their role, especially against variant surface antigens (VSA), is unclear.
Purpose of the Study:
- To investigate the immune pressure on parasites infecting infants.
- To assess if maternal antibodies to VSA shape parasite populations in infants.
- To examine the relationship between Plasmodium falciparum var gene expression and infant age.
Main Methods:
- Compared group A var gene expression in parasites from infants aged 0-12 months versus those over 12 months.
- Analyzed transcript quantity and proportional expression of group A var genes, including domain cassette 13.
- Correlated gene expression changes with antibody levels and parasitemia.
Main Results:
- Group A var gene expression, including DC13, increased with age in infants during their first year.
- This age-related increase contrasted with expression in infants over 12 months old.
- A decline in antibodies to IE surface antigens and increased parasitemia were observed during this period.
Conclusions:
- Maternally acquired antibodies likely exert selection pressure on parasites infecting infants.
- Changes in group A var gene expression suggest parasite adaptation to waning maternal immunity.
- Maternal antibodies may contribute to protecting infants against severe malaria before they develop their own immunity.
Abstract:
In sub-Saharan Africa, children below 5 years bear the greatest burden of severe malaria because they lack naturally acquired immunity that develops following repeated exposure to infections by Plasmodium falciparum. Antibodies to the surface of P. falciparum infected erythrocytes (IE) play an important role in this immunity. In children under the age of 6 months, relative protection from severe malaria is observed and this is thought to be partly due to trans-placental acquired protective maternal antibodies. However, the protective effect of maternal antibodies has not been fully established, especially the role of antibodies to variant surface antigens (VSA) expressed on IE. Here, we assessed the immune pressure on parasites infecting infants using markers associated with the acquisition of naturally acquired immunity to surface antigens. We hypothesized that, if maternal antibodies to VSA imposed a selection pressure on parasites, then the expression of a relatively conserved subset of var genes called group A var genes in infants should change with waning maternal antibodies. To test this, we compared their expression in parasites from children between 0 and 12 months and above 12 months of age. The transcript quantity and the proportional expression of group A var subgroup, including those containing domain cassette 13, were positively associated with age during the first year of life, which contrasts with above 12 months. This was accompanied by a decline in infected erythrocyte surface antibodies and an increase in parasitemia during this period. The observed increase in group A var gene expression with age in the first year of life, when the maternal antibodies are waning and before acquisition of naturally acquired antibodies with repeated exposure, is consistent with the idea that maternally acquired antibodies impose a selection pressure on parasites that infect infants and may play a role in protecting these infants against severe malaria.
