The utility of Plasmodium berghei as a rodent model for anti-merozoite malaria vaccine assessment

Anna L. Goodman, Emily K. Forbes, Andrew R. Williams, Alexander D. Douglas, Simone C. de Cassan, Karolis Bauza, Sumi Biswas, Matthew D. J. Dicks, David Llewellyn, Anne C. Moore, Chris J. Janse, Blandine M. Franke-Fayard, Sarah C. Gilbert, Adrian V. S. Hill, Richard J. Pleass, Simon J. Draper

Rodent malaria species Plasmodium yoelii and P. chabaudi have been widely used to validate vaccine approaches targeting blood-stage merozoite antigens. However, increasing data suggest the P. berghei rodent malaria may be able to circumvent vaccine-induced anti-merozoite responses. Here we confirm a failure to protect against P. berghei, despite successful antibody induction against leading merozoite antigens using protein-in-adjuvant or viral vectored vaccine delivery. No subunit vaccine approach showed efficacy in mice following immunization and challenge with the wild-type P. berghei strains ANKA or NK65, or against a chimeric parasite line encoding a merozoite antigen from P. falciparum. Protection was not improved in knockout mice lacking the inhibitory Fc receptor CD32b, nor against a Δsmac P. berghei parasite line with a non-sequestering phenotype. An improved understanding of the mechanisms responsible for protection, or failure of protection, against P. berghei merozoites could guide the development of an efficacious vaccine against P. falciparum.