Relapses originate from the latent hypnozoite forms of P. vivax that reside in the liver. Relapses and not primary infection can account for up to 90% of P. vivax malaria cases and are thus the primary driver of clinical disease and the primary source for transmission. Subunit pre-erythrocytic (PE) malaria vaccine development for P. vivax has been neglected, in part due to the limited success this approach has yielded for P. falciparum malaria. However, it has been proposed that even a partially protective PE vaccine would greatly reduce relapses and thereby have pronounced public health benefits. To test this experimentally, we developed a relapse model of P. vivax infection in liver-humanized mice. Using sporozoite infection derived from Thai P. vivax isolates, we found that we could detect relapses in the blood of the mice approximately 3 weeks after infection. We then passively transferred a partially protective dose of a neutralizing CSP-targeted antibody 24 hours prior to infection and followed the course of relapse. We found that, although no humanized mice were completely protected from primary infection, the administration of antibody greatly reduced the number of relapses. To build on this unprecedented success, we have embarked on an effort to identify additional non-CSP antibody targets that are expressed in sporozoites and will present progress on these antigens. Our ultimate goal is to develop a multiantigen subunit vaccine that is highly effective in preventing P. vivax relapses, even in the absence of complete sterilizing protection against primary infection.