Maternal antibodies that cross the placenta can interfere with the response to the malaria vaccine, which would explain its lower effectiveness in babies under five months, according to research led by the Barcelona Institute for Global Health (ISGlobal), in collaboration with seven African centers (CISM-Mozambique, IHI-Tanzania, CRUN-Burkina Faso, KHRC-Ghana, NNIMR-Ghana, CERMEL-Gabon, KEMRI-Kenya). The results published in He Infectious lancet diseasessuggests that younger babies than currently recommended by the WHO could benefit from the RTS,S and R21 malaria vaccines if they live in areas with low malaria transmission, where mothers have fewer antibodies against the parasite.
The world has reached an incredible milestone: the deployment in Africa of two first malaria vaccines-RTS,S/AS01E and the most recent R21/Matrix-M- to protect the child population against malaria caused by Plasmodium falciparum. Both vaccines are directed against a fragment of the parasite protein called circumsporozoite (CSP) and are recommended for boys and girls 5 months or older at the time of receiving the first dose.
“We know that the RTS,S/AS01E malaria vaccine is less effective in babies under five months old, but the reason for this difference is still the subject of debate,” he explains. Carlota Dobañowho directs the ISGlobal Malaria Immunology group, a center promoted by the “la Caixa” Foundation.
To investigate this, Dobaño and his team analyzed blood samples from more than 600 minors (infants between 5 and 12 weeks of age and between 5 and 17 months) who participated in the phase 3 clinical trial of RTS,S/AS01E. Using protein microarrays, they measured the antibodies against 1,000 antigens P. falciparum before vaccination to determine whether previous exposure to malaria and age influenced the response to the vaccine, that is, the level of IgG antibodies against CSP.
“This microarray approach allowed us to accurately measure the exposure to malaria at the individual levelincluding maternal exposure for babies younger than 12 weeks and past infections for babies older than five months,” it says. Didac MaciáISGlobal researcher and first author of the study.
The role of maternal antibodies
The analysis of antibodies against P. falciparum in those who had received a control vaccine instead of RTS,S/AS01E revealed a “typical exposure pattern,” with elevated levels in the first three months of life due to passive transfer of maternal antibodies across the placenta . , a decrease during the first year of life, and then a gradual increase as a result of naturally acquired infections.
In those over 5 months vaccinated with RTS,S/AS01E, antibodies resulting from a natural infection will not affect the response to the vaccine. However, in babies younger than 12 weeks, elevated levels of antibodies against P. falciparum Transmitted by the mother during pregnancy were associated with a lower response to the vaccine. This effect was particularly strong for maternal antibodies directed against the central region of the CSP protein. In contrast, infants with very low or undetectable levels of maternal IgG antibodies to CSP showed vaccine responses similar to those seen in older infants.
The mechanisms by which these maternal antibodies interfere with the vaccine are not completely known, but the same phenomenon has been observed with other vaccines, such as measles.
These results confirm something that was already suspected but had not been clearly demonstrated: despite their protective role, maternal anti-CSP antibodiesthat decrease in the first three to six months of life, may interfere with the effectiveness of the vaccine. The higher the level of malaria transmission, the more maternal antibodies are transmitted to the baby, resulting in lower vaccine effectiveness. The results also suggest that the babies under five months they can receive the vaccination with RTS,S/AS01E or R21 is low transmission areas of malaria, during outbreaks in regions without malaria, or in populations migrating to an area of high transmission.
“Our study highlights the need to consider the timing and levels of maternal malaria antibodies to improve vaccine effectiveness in the smallest and most vulnerable infants,” he says. Gemma Moncunillresearcher at ISGlobal and co-principal author of the study, along with Dobaño.
The study was funded by the National Institute of Allergy and Infectious Diseases, which is part of the National Institutes of Health (R01AI095789 and U01AI165745).
Reference
Macia D, Campo JJ, Chenjerai J et al. The effect of Plasmodium falciparum exposure and maternal antibodies against anticircumsporozoite protein in responses to RTS, S/AS01E vaccination in infants and children: an observational immunological study ancillary to a randomized phase 3 clinical trial. Lancet Inf Dis. 2024. https://doi.org/10.1016/S1473-3099(24)00527-9
