Trans-placental antibodies from the mother can suppress the immune response to malaria antibodies and this could contribute to observed lower efficacy of the malaria vaccine in infants aged below five months, study by Barcelona Institute for Global Health’s ISGlobal together with seven partners from Africa including CISM Mozambique, IHI Tanzania, CRUN Burkina Faso, KHRC Ghana, NNIMR Ghana, CERMEL Gabon, and KEMRI Kenya.
These data, presented in The Lancet Infectious Diseases, indicate that RTS,S and R21 malaria vaccines might be effective for children under the age recommended by the WHO if they live in areas with low transmission, where mothers have low levels of antibodies to the parasite.
The world has reached an incredible milestone: the initial two malaria vaccines, RTS,S/AS01 and the more modern R21/Matrix-M targeting African kids against malaria due to Plasmodium falciparum.
Both vaccines are aimed to a fragment of the parasite protein circumsporozoite (CSP) and administered to children starting from 5 months of age at the time of the first dose.
”It is clear that the RTS,S/AS01E malaria vaccine has a lower efficacy in infants aged below five months and the cause of this is what researchers are yet to fully agree on,” said Carlota Dobaño, head of the Malaria Immunology group, at ISGlobal, a centre supported by ‘la Caixa’ Foundation.
To test this, Dobaño and her team assayed blood samples from over 600 children 5–17 months of age and infants 6–12 weeks of age who had been enrolled in the phase 3 trial of the RTS,S/AS01E vaccine.
“This microarray approach lets us assimilate malaria exposure accurately at the individual level such as maternal exposure for the newborn and previous ones for the elder children,” said Didac Maciá, ISGlobal researcher and first author of the study.
Among children receiving the RTS,S/AS01E vaccine, prior exposure to natural infections did not interfere with the ability of the vaccine to elicit an immune response.
The ways these maternal antibodies interpose with these immunisations is not fully understood, although the same has been experienced in the case of other vaccines, for example measles.
Overall, these findings confirm something that was already suspected but not clearly demonstrated: While maternal anti-CSP antibodies provide protection, they may also blunter the effectiveness of the vaccine since they are shed within the first three to six months of life.
Since malaria transmission rate is high, the maternal antibodies cross over to the baby leading to compromised efficacy of the vaccine.
These findings provide additional indications that infants younger than five months RTS,S or R21 vaccination is safe and effective in low malaria transmission areas, in low malaria transmission areas during an epidemic, or in low transmission to high transmission population movement.
“These findings, our research raises awareness on timing and maternal malaria antibody levels to enhance the likelihood of successful immunisation in the youngest and most susceptible infants,” added Moncunill.
Reference: Macià D, Campo JJ, Jairoce C, Mpina M, Sorgho H, Dosoo D, et al. The effect of Plasmodium falciparum exposure and maternal anti-circumsporozoite protein antibodies on responses to RTS,S/AS01E vaccination in infants and children
