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New Insights on Maternal Antibodies and Malaria Vaccine Efficacy in Infants
Recent research led by the Barcelona Institute for Global Health (ISGlobal) has shed light on the interactions between maternal antibodies and the efficacy of malaria vaccines, particularly in infants under five months old. In collaboration with seven African research centers, the study reveals that maternal antibodies transferred through the placenta can hinder the immune response to malaria vaccines such as RTS,S and R21. Published in Lancet Infectious Diseases, this study proposes that infants in areas with low malaria transmission might actually benefit from vaccination at an earlier age than is currently recommended by the World Health Organization (WHO).
To date, significant progress has been made in the fight against malaria, with the introduction of the RTS,S/AS01E and R21/Matrix-M vaccines, specifically designed to protect African children against infections caused by Plasmodium falciparum. Both vaccines focus on a specific protein segment of the parasite known as circumsporozoite (CSP) and are currently suggested for administration to children starting at five months of age.
“Although we recognize that RTS,S/AS01E has reduced effectiveness in infants under five months, the underlying reasons for this discrepancy remain under investigation,” explains Carlota Dobaño, head of the Malaria Immunology group at ISGlobal, an initiative supported by “la Caixa” Foundation.
In order to explore this matter further, Dobaño and her team conducted an analysis of blood samples from over 600 participants in a phase 3 clinical trial of RTS,S/AS01E. Their methodology involved using protein microarrays to evaluate antibody levels against 1,000 different P. falciparum antigens prior to vaccination, aiming to decipher the influence of age and past malaria exposure on IgG antibody responses to the vaccine.
“Utilizing this microarray technology enabled us to gain a precise understanding of individual malaria exposure, factoring in maternal influence for infants and previous infections for older children,” remarks Didac Maciá, an ISGlobal researcher and the study’s principal author.
The Impact of Maternal Antibodies
An examination of antibody profiles from children who received control vaccines rather than RTS,S/AS01E revealed a characteristic “exposure” pattern: infants exhibited elevated antibody levels in the initial three months due to passive maternal transfer, followed by a decrease in the first year, and a gradual rise attributable to naturally acquired infections.
In the context of children vaccinated with RTS,S/AS01E, it was found that antibodies stemming from past infections did not significantly affect vaccine efficacy. However, for infants, high levels of maternal antibodies, particularly targeting the CSP protein, were linked to diminished vaccine responses. Notably, infants who had low or non-detectable maternal anti-CSP antibodies displayed vaccine responses comparable to older children.
While the precise molecular mechanisms through which maternal antibodies interfere with vaccine effectiveness remain largely unclear, similar patterns have been observed with other vaccines, such as those for measles.
These findings corroborate previously held hypotheses about the role of maternal antibodies. Despite serving a protective function, maternal anti-CSP antibodies, which typically wane in the first three to six months of life, may actually lower vaccine efficacy. This effect is likely magnified in regions with higher malaria transmission rates, where greater maternal antibody levels are transferred to infants. The results also imply that younger infants may find advantage in receiving RTS,S or R21 vaccinations during periods of low malaria transmission or in non-endemic regions experiencing malaria outbreaks.
“Our research underscores the importance of considering both the timing of vaccination and maternal malaria antibody levels to enhance the effectiveness of vaccines for our youngest and most vulnerable populations,” concludes Gemma Moncunill, another ISGlobal researcher and co-senior author of the study alongside Dobaño.
This investigation received backing from the National Institute of Allergy and Infectious Diseases, a division of the National Institutes of Health, through grants R01AI095789 and U01AI165745.
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