Plasmodium vivax is the most widespread species and dominant Plasmodium parasite causing human malaria outside of sub-Saharan Africa, continuing to pose a major global health burden due to its high morbidity and mortality rates. Effective interventions against P. vivax remain a significant challenge due to its distinct biological features. Although vaccines exist for Plasmodium falciparum, the dominant cause of malaria in Africa, there is currently no licensed vaccine for P. vivax, and only limited antigen candidates have reached clinical trials. Development of highly efficacious malaria vaccines are urgently required to support global elimination and sustain elimination long-term. Naturally acquired clinical immunity, driven by strong antibody responses to Plasmodium parasites, develops through repeated exposure in endemic areas. Studying natural acquired immunity to malaria to provide a promising insight for vaccine development. Parasite-specific antibodies play a critical role in naturally acquired protective immunity to malaria. Most research on protective antibodies against P. vivax has focused on IgG while the protective role of IgM has received limited attention. This study will focus on investigating whether IgG and IgM antibody responses against blood stage and liver stage antigens of P. vivax are associated with protection against clinical malaria across transmission settings. IgG and IgM levels against a panel of 61 P. vivax antigens were simultaneously quantified using the Luminex INTELLIFLEX platform in plasma samples from both low (Brazilian cohort n = 265, Thai cohort n = 80) and high transmission settings (PNG cohort n = 184). Participants were followed for 12 months and screened monthly for clinical episodes and infection status. Statistical analyses are underway to assess the association of antibody responses with protection against subsequent clinical malaria over the following period. This work will highlight how associations with protection differ between IgG and IgM responses against a 61 P. vivax antigens panel.