A NOVEL approach to malaria immunisation using genetically attenuated parasites (GAP) has demonstrated promising efficacy, according to results from a double-blind, controlled clinical trial. The study explored the safety, immune response, and protective efficacy of a second-generation genetically modified Plasmodium falciparum malaria parasite (GA2).
The trial, conducted in two stages, tested the effects of immunisation through mosquito bites. In the initial safety phase, participants were exposed to bites from 15 or 50 mosquitoes infected with the GA2 parasite. In the second phase, healthy adults with no prior history of malaria were randomly assigned to receive three immunisations with either GA2, an earlier-generation parasite (GA1), or a placebo via bites from mosquitoes carrying uninfected parasites.
Adverse events were consistent across all groups, indicating a comparable safety profile for GA2. Importantly, protective efficacy against controlled malaria infection was significantly higher in the GA2 group. Of the nine participants receiving GA2, eight (89%) showed protection against blood-stage parasitaemia, compared to just one of eight participants (13%) in the GA1 group and none in the placebo group.
In-depth immune analysis revealed that GA2 recipients exhibited a higher frequency of malaria-specific polyfunctional CD4+ and Vδ2+ γδ T cells compared to those receiving GA1. However, both GA2 and GA1 elicited similar antibody responses targeting the malaria circumsporozoite protein.
The study highlights the potential of GA2 to offer robust and durable protection against malaria. Unlike existing subunit vaccines, which provide only modest and short-lived defence, this approach leverages live-attenuated parasites for stronger immune activation. Further investigation will be needed to evaluate the long-term efficacy and broader applicability of GA2.
Ada Enesco, EMJ
Reference
Lamers OAC et al. Safety and efficacy of immunization with a late-liver-stage attenuated malaria parasite. N Engl J Med. 2024;391(20):1913-1923.
