Browsing by Author "Rayner, Julian C."

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    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 Medicine
    Background 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.
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    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 Medicine
    Background: 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.
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    Synergistic malaria vaccine combinations identified by systematic antigen screening
    (National Academy of Sciences, 2017-11-07) Bustamante, Leyla Y.; Powell, Gareth T.; Lin, Yen-Chun; Macklin, Michael D.; Cross, Nadia; Kemp, Alison; Cawkill, Paula; Sanderson, Theo; Crosnier, Cecile; Muller-Sienerth, Nicole; Doumbo, Ogobara K.; Traore, Boubacar; Crompton, Peter D.; Cicuta, Pietro; Tran, Tuan M.; Wright, Gavin J.; Rayner, Julian C.; Medicine, School of Medicine
    Malaria still kills hundreds of thousands of children each year. Malaria vaccine development is complicated by high levels of parasite genetic diversity, which makes single target vaccines vulnerable to the development of variant-specific immunity. To overcome this hurdle, we systematically screened a panel of 29 blood-stage antigens from the most deadly human malaria parasite, Plasmodium falciparum. We identified several targets that were able to inhibit erythrocyte invasion in two genetically diverse strains. Testing these targets in combination identified several pairs that blocked invasion more effectively in combination than in isolation. Video microscopy and studies of natural immune responses to malaria in patients suggest that targeting multiple steps in invasion is more likely to produce a synergistic vaccine response., A highly effective vaccine would be a valuable weapon in the drive toward malaria elimination. No such vaccine currently exists, and only a handful of the hundreds of potential candidates in the parasite genome have been evaluated. In this study, we systematically evaluated 29 antigens likely to be involved in erythrocyte invasion, an essential developmental stage during which the malaria parasite is vulnerable to antibody-mediated inhibition. Testing antigens alone and in combination identified several strain-transcending targets that had synergistic combinatorial effects in vitro, while studies in an endemic population revealed that combinations of the same antigens were associated with protection from febrile malaria. Video microscopy established that the most effective combinations targeted multiple discrete stages of invasion, suggesting a mechanistic explanation for synergy. Overall, this study both identifies specific antigen combinations for high-priority clinical testing and establishes a generalizable approach that is more likely to produce effective vaccines.