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Item The Kinetics of Antibody Responses to Plasmodium Vivax Vaccine Candidate Antigens in Brazilians with Acute Vivax Malaria(2022-05) Tashi, Tenzin; Tran, Tuan M.; Bauer, Margaret E.; Hoang, Quyen Q.Plasmodium vivax malaria is geographically widespread and remains a significant public health burden in the Americas, Southeast Asia, and the western Pacific. In order to achieve the end goal of malaria eradication, a highly effective vaccine targeting P. vivax is urgently needed. Unlike pre-erythrocytic vaccines that aim to confer sterile immunity that prevents malaria infection altogether, Plasmodium vivax blood-stage vaccines aim to confer clinical immunity that protects against malarial disease by controlling parasitemia and mitigating the symptomatic manifestations of malaria after infection. To design an effective P. vivax blood-stage vaccine, it is essential to understand the acquisition and longevity of natural humoral immune responses against promising P. vivax blood-stage vaccine candidate antigens. We hypothesize that acute vivax malaria induces differential humoral immune responses against P. vivax antigens that exhibit antigen-specific kinetic and compositional profiles, which can be used to identify vaccine candidates that elicit durable humoral responses. Therefore, we compared the kinetic profiles and half-lives of naturally acquired IgG antibodies reactive against nine promising P. vivax blood-stage vaccine candidate antigens up to 180 days post-infection in Brazilians with acute vivax malaria. Naturally acquired IgG antibodies against these antigens have previously been associated with a reduced risk of vivax malaria. Among the P. vivax antigens evaluated, the merozoite antigen Pv12 elicited the most durable IgG antibodies, whereas the DBP-FL elicited the most short-lived responses. Neither patient age nor prior malaria exposure significantly correlated with the magnitude and durability of IgG responses to any P. vivax antigen. Seropositivity, against Pv12, was generally maintained for at least 30 days after acute vivax malaria. These findings suggest that a blood-stage vaccine targeting Pv12 may benefit from boosting IgG antibodies against this antigen after natural vivax “breakthrough” infections. Further studies will be needed to determine the Pv12-specific memory B cell response as well as the functional role for naturally acquired Pv12-specific antibodies in reducing parasitemia and/or clinical disease. In summary, the current study has provided insight into the longevity of IgG antibody responses to important P. vivax antigens after an acute malaria episode.Item Longitudinal IgG antibody responses to Plasmodium vivax blood-stage antigens during and after acute vivax malaria in individuals living in the Brazilian Amazo(PLoS, 2022-11-23) Tashi, Tenzin; Upadhye, Aditi; Kundu, Prasun; Wu, Chunxiang; Menant, Sébastien; Soares, Roberta Reis; Ferreira, Marcelo U.; Longley, Rhea J.; Mueller, Ivo; Hoang, Quyen Q.; Tham, Wai-Hong; Rayner, Julian C.; Scopel, Kézia K. G.; Lima-Junior, Josué C.; Tran, Tuan M.; Medicine, School of MedicineBackground To make progress towards malaria elimination, a highly effective vaccine targeting Plasmodium vivax is urgently needed. Evaluating the kinetics of natural antibody responses to vaccine candidate antigens after acute vivax malaria can inform the design of serological markers of exposure and vaccines. Methodology/Principal findings The responses of IgG antibodies to 9 P. vivax vaccine candidate antigens were evaluated in longitudinal serum samples from Brazilian individuals collected at the time of acute vivax malaria and 30, 60, and 180 days afterwards. Antigen-specific IgG correlations, seroprevalence, and half-lives were determined for each antigen using the longitudinal data. Antibody reactivities against Pv41 and PVX_081550 strongly correlated with each other at each of the four time points. The analysis identified robust responses in terms of magnitude and seroprevalence against Pv41 and PvGAMA at 30 and 60 days. Among the 8 P. vivax antigens demonstrating >50% seropositivity across all individuals, antibodies specific to PVX_081550 had the longest half-life (100 days; 95% CI, 83–130 days), followed by PvRBP2b (91 days; 95% CI, 76–110 days) and Pv12 (82 days; 95% CI, 64–110 days). Conclusion/Significance This study provides an in-depth assessment of the kinetics of antibody responses to key vaccine candidate antigens in Brazilians with acute vivax malaria. Follow-up studies are needed to determine whether the longer-lived antibody responses induced by natural infection are effective in controlling blood-stage infection and mediating clinical protection.Item Longitudinal IgG antibody responses to Plasmodium vivax blood-stage antigens during and after acute vivax malaria in individuals living in the Brazilian Amazon(Public Library of Science, 2022-11-23) Tashi, Tenzin; Upadhye, Aditi; Kundu, Prasun; Wu, Chunxiang; Menant, Sébastien; Reis Soares, Roberta; Ferreira, Marcelo U.; Longley, Rhea J.; Mueller, Ivo; Hoang, Quyen Q.; Tham, Wai-Hong; Rayner, Julian C.; Scopel, Kézia K. G.; Lima-Junior , Josué C.; Tran, Tuan M.; Medicine, School of MedicineBackground: To make progress towards malaria elimination, a highly effective vaccine targeting Plasmodium vivax is urgently needed. Evaluating the kinetics of natural antibody responses to vaccine candidate antigens after acute vivax malaria can inform the design of serological markers of exposure and vaccines. Methodology/principal findings: The responses of IgG antibodies to 9 P. vivax vaccine candidate antigens were evaluated in longitudinal serum samples from Brazilian individuals collected at the time of acute vivax malaria and 30, 60, and 180 days afterwards. Antigen-specific IgG correlations, seroprevalence, and half-lives were determined for each antigen using the longitudinal data. Antibody reactivities against Pv41 and PVX_081550 strongly correlated with each other at each of the four time points. The analysis identified robust responses in terms of magnitude and seroprevalence against Pv41 and PvGAMA at 30 and 60 days. Among the 8 P. vivax antigens demonstrating >50% seropositivity across all individuals, antibodies specific to PVX_081550 had the longest half-life (100 days; 95% CI, 83-130 days), followed by PvRBP2b (91 days; 95% CI, 76-110 days) and Pv12 (82 days; 95% CI, 64-110 days). Conclusion/significance: This study provides an in-depth assessment of the kinetics of antibody responses to key vaccine candidate antigens in Brazilians with acute vivax malaria. Follow-up studies are needed to determine whether the longer-lived antibody responses induced by natural infection are effective in controlling blood-stage infection and mediating clinical protection.