Do children develop antibodies against the VAR2CSA malaria protein?

Children develop antibodies to VAR2CSA, a protein on the surface of the Plasmodium falciparum malaria parasite, though generally at low levels. They tend to recognize specific Duffy-binding-like (DBL) domains like DBL2 and DBL4. Interestingly, teenage girls also showed recognition of the ID1-ID2a region of VAR2CSA. This contrasts with pregnant women, who typically have high levels of IgG to DBL3, DBL5, and full-length VAR2CSA protein (FV2).

Is there a link between VAR2CSA antibody levels and severe malaria in children?

The study found that children with severe malaria did not have higher levels of antibodies to VAR2CSA compared to healthy children. Instead, children with severe malaria had higher levels of IgG to merozoite antigens. This suggests that VAR2CSA-specific immunity may not be a primary factor in protecting children against severe malaria.

Why is Plasmodium falciparum's VAR2CSA protein so important in malaria infections, especially during pregnancy?

The Plasmodium falciparum parasite uses antigenic variation to evade the immune system, changing surface proteins like VAR2CSA. VAR2CSA is crucial because it allows the parasite to bind to the placenta, leading to complications during pregnancy. Understanding how children develop antibodies to different parts of VAR2CSA can offer insights into designing strategies to protect pregnant women.

How do antibody responses to VAR2CSA differ between children and pregnant women, and what does this imply?

This research highlights significant differences in antibody responses to VAR2CSA between children and pregnant women. Children primarily target DBL2 and DBL4 domains, while pregnant women have stronger responses to DBL3, DBL5, and FV2. This suggests different exposure pathways or immune responses at different stages of life. Further research could explore why these differences exist and how to leverage childhood immunity to protect pregnant women.

Besides antibodies, what other immune responses might protect children from severe malaria, and what future research is needed?

The study focused on antibody responses. Future studies could investigate other immune mechanisms, such as T cell responses, that might contribute to protection against severe malaria in children. Understanding the full scope of the immune response could lead to the development of more effective interventions. Further research is needed to assess the duration and effectiveness of these antibodies and how they might be boosted through vaccination or other interventions.

Children fighting malaria with protective antibodies.

Malaria Antibodies: What Kids Can Teach Us About Pregnancy Protection

Reese Marlowe in Health & Wellness December 2025 • 4 min read.

"New research explores how children develop antibodies to malaria, potentially unlocking secrets to better protecting pregnant women."

Malaria is a global health threat, especially for pregnant women and children. The parasite Plasmodium falciparum has developed a sneaky way to evade our immune systems: antigenic variation. This means the parasite can change its surface proteins, making it difficult for our bodies to recognize and fight it off. One of these surface proteins, VAR2CSA, is crucial for the parasite to bind to the placenta, leading to serious complications during pregnancy.

For years, scientists thought that antibodies (Abs) against VAR2CSA were primarily produced during pregnancy. However, recent studies have found these antibodies in children and men, challenging this idea. This raises a critical question: How and when do children develop these antibodies outside of pregnancy, and could this knowledge help us protect pregnant women?

A new study published in Malaria Journal has investigated the development of antibodies to VAR2CSA in Cameroonian children and teenagers. The researchers aimed to understand how frequently these antibodies are produced in children, their specificity, and whether children with severe malaria are more likely to have them. By unraveling these mysteries, we can potentially design better strategies to combat malaria in pregnancy and beyond.

Decoding Childhood Malaria Antibodies: Key Findings

Children fighting malaria with protective antibodies.

The study involved analyzing blood samples from 193 children (ages 1-15) from rural Cameroonian villages and 160 children with severe malaria from the city. Researchers measured antibody responses to various parts of VAR2CSA, including specific Duffy-binding-like (DBL) domains and the full-length VAR2CSA protein (FV2).

Here's what they discovered:

Low Levels in Children: Children generally had low levels of antibodies to VAR2CSA. However, antibodies to FV2 were even rarer in teenagers.
Targeted DBL Domains: Children were more likely to recognize DBL2 (56-70%) and DBL4 (50-60%) domains, while pregnant women tend to have high levels of IgG to DBL3, DBL5, and FV2.
Teenage Girls and ID1-ID2a: A significant portion (67%) of teenage girls recognized the ID1-ID2a region of VAR2CSA.
Severe Malaria Link: Children with severe malaria had higher levels of IgG to merozoite antigens (proteins on the surface of the malaria parasite) but not to VAR2CSA, compared to healthy children.

These results suggest that children, including teenage girls, do develop antibodies to VAR2CSA domains and FV2. However, these antibody levels are much lower than those typically needed to protect pregnant women from placental malaria. Furthermore, the types of antibody responses to DBL domains differ between children and pregnant women. Interestingly, children with severe malaria did not have higher antibody levels to VAR2CSA compared to healthy children, suggesting that VAR2CSA-specific immunity may not play a significant role in protection against severe disease in this age group.

Implications and Future Directions

This study provides valuable insights into the development of VAR2CSA antibodies in children, highlighting the differences in antibody responses between children and pregnant women. The finding that children with severe malaria do not have higher VAR2CSA antibody levels suggests that other immune mechanisms may be more important in protecting against severe disease in this age group.

The fact that a significant proportion of teenage girls recognize the ID1-ID2a region of VAR2CSA is particularly interesting, as this region is currently being explored as a vaccine target. However, further research is needed to understand whether these antibodies can provide any protection against placental malaria in future pregnancies.

Ultimately, understanding the nuances of VAR2CSA antibody development in children can pave the way for designing more effective malaria prevention strategies for everyone, especially pregnant women and their unborn children. This research underscores the complexity of malaria immunity and the need for continued investigation to develop targeted interventions.