The RTS, S vaccine against malaria could favor the production of a series of protective antibodies after infection by the parasite, according to a study led by the Global Health Institute of Barcelona. The results, published in BMC Medicine, identify which antigens (or protein fragments) could be included in the design of future, more effective, multivalent vaccines.
Immunity against a pathogen can be acquired naturally (that is, after natural exposure to it) or thanks to a vaccine. Occasionally, the mechanisms behind these two types of immunity are not the same, particularly in the case of parasites with complex life cycles, such as Plasmodium falciparum, the parasite that causes malaria.
The team of Carlota Dobaño, a researcher at the Institute of Global Health of Barcelona (ISGlobal), has been studying for several years the immune response induced by RTS, S, the most advanced malaria vaccine to be implemented this year on a large scale in sub-Saharan Africa.
In this study, they wanted to evaluate how vaccination affects the natural immunity acquired subsequently against the parasite. “So far, the vast majority of RTS, S studies have focused on evaluating specific responses of the vaccine, and not evaluating its influence on responses to other parasite antigens,” explains Gemma Moncunill, one of the authors of the study. The RTS, S vaccine only contains one parasite antigen: a fragment of the CSP protein.
The research team analyzed serum samples obtained from a total of 195 children, vaccinated or controls, who participated in phase 3 of the clinical trial of RTS, S and those who were followed for 12 months. Of these, 78 were from Kintampo, Ghana, an area with high malaria transmission, and 115 were from Manhiça, Mozambique, where transmission is low to moderate.
The experts studied the levels and type of antibodies directed against a total of 38 protein fragments (or antigens) of P. falciparum, including the CSP protein, before and after vaccination.
They found three profiles of antibody responses to these antigens: those that decrease after vaccination, those that do not change, and those that increase. Those in the first group in general are markers of exposure to the parasite and were associated with an increased risk of contracting malaria.
Those in the third group were associated with greater protection —they reduced the risk of contracting malaria in half. These protective antibodies mostly recognize antigens expressed by the phases of the parasite that circulate in the blood and infect the red blood cells.
The researchers think that the partial efficacy of RTS, S allows, when there is subsequent exposure to the parasite, maintaining low levels of infection enough to favor the production of these protective antibodies, says Carlota Dobaño . “This effect would be appreciated especially in regions with moderate levels of transmission,” she adds.
Importantly, these results indicate that the antigens in question could be included in future, more effective, multivalent vaccines.