MALARIA: Why the vaccine is less effective in infants

The deployment of anti-malaria vaccines -RTS,S/AS01E and R21/Matrix-M- to protect African children against malaria caused by Plasmodium falciparum – which target part of the parasitic protein called circumsporozoite (CSP), in children aged 5 months or more at the time of the first dose, constitutes an essential step in the fight against the disease. However, as one of the lead authors, Dr. Carlota Dobaño, an immunologist specializing in malaria at ISGlobal, notes: “the RTS,S/AS01E malaria vaccine is less effective in infants under 5 months of age, but this less effective in infants is still subject to debate.

To answer this question, the ISGlobal team collaborated with 7 African centers (CISM-Mozambique, IHI-Tanzania, CRUN-Burkina Faso, KHRC-Ghana, NNIMR-Ghana, CERMEL-Gabon, KEMRI-Kenya). This research, the first of its kind, leads to an important conclusion in the fight against malaria: children younger than those currently recommended by the WHO could benefit from the RTS,S and R21 malaria vaccines when they live in low-risk areas. transmission of malaria, where mothers have fewer antibodies against the parasite.

The study analysis of blood samples from more than 600 children (aged 5 to 17 months) and infants (aged 6 to 12 weeks) as part of a phase III clinical trial of the RTS,S/AS01E vaccine. The analysis measured these children’s antibody levels 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.

Analysis of anti-P antibodies. falciparum reveals:

• in children who received a control vaccine instead of RTS,S/AS01E: a typical “exposure” signature, with elevated levels during the first 3 months of life due to passive transfer of maternal antibodies across the placenta , a decline during the first year of life, then a gradual increase due to naturally acquired infections.
• In children vaccinated with RTS,S/AS01E; antibodies induced by natural infections do not affect the vaccine response;
• in infants, high levels of anti-P antibodies. falciparum, probably transmitted by their mother during pregnancyappear 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 IgG show higher vaccine responses.

In other words,

The higher the levels of antibodies transmitted by the mother, the less marked the vaccine response.

What molecular mechanisms? If the underlying mechanisms are not elucidated, scientists note that the same phenomenon has been observed with other vaccines such as that against measles.

Finally, we note that despite their protective function, maternal antibodies, which decrease during the first 3 to 6 months of life, can interfere with the effectiveness of the vaccine.

Data that highlight the need to take into account maternal anti-malaria antibody levels to optimize the effectiveness of vaccination in infants.