A Study Identifies Antibodies Correlated with Protection against Malaria among Two-Year Old Infants

An international study led by ISGlobal, an institution supported by “la Caixa” Foundation, describes for the first time the dynamics of the antibody response against Plasmodium falciparum during the first two years of life in Mozambican children, and identifies antibodies correlated with protection. The results, published in Clinical Infectious Diseases, highlight the importance of age and parasite exposure levels when studying correlates of protective immunity.

In the last decade, many regions have seen a sharp decrease in malaria cases and are focussing efforts on its elimination. In these settings, a highly efficacious vaccine to compensate for the loss of natural immunity that occurs when malaria transmission decreases, would be very useful (the WHO approved RTS,S vaccine confers limited protection). In order to identify malaria vaccine candidates, a key criterion is finding parasite proteins (antigens) that are targets of natural immunity, and confirming that these antibodies are associated with protection in the target population.  

The study, performed in Mozambique, aimed to identify antibodies to the malaria parasite P. falciparum in serum samples of children age two or younger, all of them previously exposed to the disease (84% of the samples). They measured the type and levels of antibodies against 23 parasite antigens as well as their association with the risk of developing malaria during a five-year period.   

They found that certain IgG antibodies (to CyrPA, DBL3x, DBL5e, EBA140III-V antigens) were associated with a lower risk of clinical malaria, but only in 24 month-old children. In contrast, some IgM antibodies (to EBA175-PfF2) correlated with higher risk. Functional assays showed that complement fixation (by anti-MSP1 antibodies) was also associated with protection. 

“These associations could be identified because we included only malaria-exposed children and we considered different exposure levels” explains first author of the study Aida Valmaseda, from ISGlobal.   

“This study highlights the importance of considering exposure heterogeneity in the development of future vaccines” adds Alfredo Mayor, ISGlobal researcher and study coordinator, “and this will become more relevant as malaria transmission declines, since the possibility of including non-exposed individuals in clinical trials will increase.”  

Reference