An international study led by ISGlobal, an institution supported by the “la Caixa” Banking Foundation, identifies immune responses associated with protection – or lack of protection- against malaria after immunization with the vaccine candidate RTS,S, also known as Mosquirix™. The study, published in Clinical Infectious Diseases, was carried out by MalVIC (RTS,S Malaria Vaccine Immunology Consortium) and may inform efforts to improve the efficacy of this and future vaccines, particularly in infants.
The efficacy of the most advanced malaria candidate vaccine, RTS,S against clinical malaria is moderate, and lower in infants between 6 and 12 weeks of age (31%) than in children between 5 and 17 months of age (56%), over the first year of follow-up. The reasons for this remain unknown but could be due to differences in the magnitude or type of immune responses induced by the vaccine. The goal of this study was to identify cellular immunity-based correlates of malaria protection associated with RTS,S vaccination.
The authors performed a case-control study nested within the multicenter African RTS,S Phase 3 efficacy and safety trial, with at least 200 vaccinated or non-vaccinated infants and children from Bagamoyo (Tanzania), Lambaréné (Gabon) and Manhiça (Mozambique), some of which subsequently developed clinical malaria. The authors used an assay that permits the simultaneous analysis of multiple cytokines (proteins secreted by immune cells) to determine the cellular immune response from blood samples obtained one month after the last immunization. They found that IL5 (a cytokine characteristic of an anti-inflammatory Th2 type response) was associated with a risk of developing malaria despite vaccination, while a pro-inflammatory Th1-type response (characterized by an increase in IFN-g, IL-15 and GM-CSF cytokines) was associated with protection against subsequent malaria. They also found that, while the vaccine induced high levels of Th1 cytokines in children, this increase was not observed in infants.
“It is thought that the immune response in newborns is biased towards a Th2-like profile” explains Gemma Moncunill, lead author of the study, “which could explain the lower vaccine efficacy in younger babies”. “These results indicate that we need to find adjuvants (substances that enhance the immune response) that boost Th1 type responses during the first months of life” adds Carlota Dobaño, coordinator of the study.
The study results also suggest that the immune status of the baby or child (previous exposure to the malaria parasite, other vaccines, etc.) could modulate the vaccine’s protective efficacy. “These results go beyond malaria and underline the need to understand the impact of the basal immune status and other factors that may modulate any pediatric vaccine responses in Africa” concludes Dobaño.
The study was supported by GSK and received funds from the PATH Malaria Vaccine Initiative, NIH-NIAID under Award Number R01AI095789, the Ministerio de Economía y Competitividad (Instituto de Salud Carlos III), and the Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR).The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health and other funders.
Moncunill G, Mpina M, Nhabomba AJ, et al. Distinct Th1 and Th2 cellular responses associated with malaria protection and risk in RTS,S/AS01E vaccines. Clinical Infect Dis. 2017, 13 May doi.org/10.1093/cid/cix429