A study shows for the first time that, the greater the avidity of certain antibodies generated by the RTS,S/AS01E Malaria Vaccine, the greater the protection conferred. The study, published in Nature Communications, provides important information to guide the design of more effective future vaccines.
The quantity and quality of antibodies directed against the final end of the CSP protein of the malaria-causing parasite is a good protection marker for the RTS,S/AS01E Malaria Vaccine, according to a study led by ISGlobal, in collaboration with the Bagamoyo Research and Training Center of the Ifakara Health Institute (Tanzania), the Kintampo Health Research Center (Ghana), the Institut de Recherche en Sciences de la Sante de Nanoro (Burkina Faso), and the Swiss Tropical and Public Health Institute (Switzerland), among others.
Most vaccines contain inactivated pathogens, or fragments thereof, against which the organism generates protective antibodies. This is not the case for RTS, S, which has the merit of being the first malaria vaccine approved for large-scale trials in Africa, but which confers partial and limited protection over time. During the last years, the group of Carlota Dobaño, researcher of ISGlobal, has tried to understand why, and identify markers associated to the vaccine’s protection.
The RTS, S vaccine contains a fragment of the CSP protein of P. falciparum that goes from the central part, characterized by a series of amino acid repeats (NANP region), to one end of it (C-terminal). In this study, Dobaño and his team concentrated their efforts on analyzing not only the amount of antibodies against the NANP region and the C-terminal region, but also their avidity (that is, the strength with which they bind to their ligand).
For this, they used samples of more than 1,000 babies (between 6 and 12 weeks of age) and girls and boys (between 5 and 17 months of age), vaccinated or not during the phase 3 clinical trial of the RTS, S, in an area of low transmission of the disease (Bagomoyo in Tanzania) and in two high transmission zones (Nanoro in Burkina Faso and Kintampo in Ghana).
New and better vaccines
The results, published in Nature Communications, show for the first time that vaccination not only induces a strong increase in the amount of antibodies against both regions of CSP, but also in their avidity. These increases are stronger in girls and boys than in babies, which may explain why children are better protected.
“In terms of protection, the avidity of antibodies against the C-terminal part is more important than the quantity, while for anti-NANP antibodies it is more a matter of quantity than quality,” explains Dobaño. The results also indicate that, when a child has already been exposed to malaria (and therefore already has antibodies against CSP), the protective effect of the vaccine is less.
“This indicates that the vaccine will better protect children who have been less exposed to the parasite, for example those who live in areas of low transmission,” adds Dobaño. The team concludes that understanding the mechanisms associated with the partial protection induced by the RTS, S will help guide the design of new and better vaccines.