Maternal antibodies passed across the placenta can hinder the efficacy of malaria vaccines in infants under five months, suggesting adjustments to vaccination timing.

According to research led by the Barcelona Institute for Global Health (ISGlobal) in partnership with seven African centers, maternal antibodies transferred through the placenta can hinder the effectiveness of the malaria vaccine, explaining its reduced efficacy in infants under five months. Published in Lancet Infectious Diseases, the findings suggest that children younger than the current WHO recommendations might benefit from the RTS, S and R21 malaria vaccines in regions with low malaria transmission, where maternal antibody levels against the parasite are lower (1^✔ ✔Trusted Source
The effect of Plasmodium falciparum exposure and maternal anti-circumsporozoite protein antibodies on responses to RTS,S/AS01E vaccination in infants and children: an ancillary observational immunological study to a phase 3, randomised clinical trial

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Milestone in Malaria Prevention

The world has achieved a significant milestone with the introduction of the first two malaria vaccines—RTS, S/AS01E and the newer R21/Matrix-M—designed to protect African children from malaria caused by Plasmodium falciparum. Both vaccines target a segment of the parasite protein known as circumsporozoite (CSP) and are currently recommended for children aged 5 months and older at the time of their first dose.

Utilizing Protein Microarrays for Antibody Measurement

“We know that the RTS, S/AS01E malaria vaccine is less effective in infants under five months of age, but the reason for this difference is still debated,” says Carlota Dobaño, who leads the Malaria Immunology group at ISGlobal, a center supported by “la Caixa” Foundation.

To investigate this, Dobaño and her team analyzed blood samples from more than 600 children (age 5-17 months) and infants (age 6-12 weeks) who participated in the phase 3 clinical trial of RTS, S/AS01E. Using protein microarrays, they measured antibodies against 1,000 P. falciparum antigens before vaccination to determine if and how malaria exposure and age affected IgG antibody responses to the malaria vaccine.

“This microarray approach allowed us to accurately measure malaria exposure at the individual level, including maternal exposure for infants and past infections for older children,” says Didac Maciá, ISGlobal researcher and first author of the study.

Vaccine Responses in Infants with Varying Maternal Antibody Levels

The analysis of antibodies to P. falciparum in children who had received a control vaccine instead of RTS, S/AS01E revealed a typical “exposure” signature, with high levels in the first three months of life due to the passive transfer of maternal antibodies through the placenta, a decline during the first year of life, and then a gradual increase as a result of naturally acquired infections.

In children vaccinated with RTS,S/AS01E, antibodies induced by natural infections did not affect the vaccine response. However, in infants, high levels of antibodies to P. falciparum, presumably passed from their mothers during pregnancy, correlated with reduced vaccine responses. This effect was particularly strong for maternal anti-CSP antibodies targeting the central region of the protein. Conversely, infants with very low or undetectable maternal anti-CSP IgGs exhibited similar vaccine responses as those observed in children.

The molecular mechanisms underlying this interference by maternal antibodies are not fully understood, but the same phenomenon has been observed with other vaccines such as measles.

Impact of Malaria Transmission on Vaccine Effectiveness

Overall, these findings confirm something that was already suspected but not clearly demonstrated: despite their protective function, maternal anti-CSP antibodies, which decline within the first three to six months of life, may interfere with vaccine effectiveness. The higher the level of malaria transmission, the more maternal antibodies are transmitted to the baby, resulting in lower vaccine effectiveness. These findings further suggest that infants below five months of age may benefit from RTS, S or R21 vaccination in low malaria transmission settings, during outbreaks in malaria-free regions, or in populations migrating from low to high transmission settings.

“Our study highlights the need to consider timing and maternal malaria antibody levels to improve vaccine efficacy for the youngest and most vulnerable infants,” says Gemma Moncunill, ISGlobal researcher and co-senior author of the study, together with Dobaño.

Reference:

1. The effect of Plasmodium falciparum exposure and maternal anti-circumsporozoite protein antibodies on responses to RTS,S/AS01E vaccination in infants and children: an ancillary observational immunological study to a phase 3, randomised clinical trial – (https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(24)00527-9/abstract)

Source-Eurekalert