Partial protection against P. vivax infection diminishes hypnozoite burden and blood-stage relapses

Latent forms of Plasmodium vivax, called hypnozoites, cause malaria relapses from the liver into the blood-streamand are a major obstacle to malaria eradication. To experimentally assess the impact of a partially protective pre-erythrocytic vaccine on reducing Plasmodium vivax relapses, we developed a liver-humanized mouse model that allows monitoring of relapses directly in the blood. We passively infused these mice with a suboptimal dose of an antibody that targets the circumsporozoite protein prior to challenge with P. vivax sporozoites. Although this regimen did not completely prevent primary infection, antibody-treated mice experienced 62% fewer relapses. The data constitute unprecedented direct experimental evidence that suboptimal efficacy of infection-blocking antibodies, while not completely preventing primary infection, has a pronounced benefit in reducing the number of relapses. These findings suggest that a partially efficacious pre-erythrocytic Plasmodium vivax vaccine can have a disproportionately high impact in positive public health outcomes.

Automated summary

This study developed a liver-humanized mouse model to experimentally assess the impact of a partially protective pre-erythrocytic vaccine on reducing Plasmodium vivax relapses. Results showed that although the antibody treatment did not completely prevent primary infection, it significantly reduced the number of relapses, indicating the potential for a partially efficacious vaccine in positive public health outcomes.