Publications by authors named "Xi Zen Yap"

Cellular aging is difficult to study in individuals with natural infection, given the diversity of symptom duration and clinical presentation, and the high interference of aging-related processes with host and environmental factors. To address this challenge, we took advantage of the controlled human malaria infection (CHMI) model. This approach allowed us to characterize the relationship among cellular aging markers prior, during and post malaria pathophysiology in humans, controlling for infection dose, individual heterogeneity, previous exposure and co-infections.

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Controlled human malaria infection (CHMI) is an established model in clinical malaria research. Upon exposure to Plasmodium falciparum parasites, malaria-naive volunteers differ in dynamics and composition of their immune profiles and subsequent capacity to generate protective immunity. CHMI volunteers are either inflammatory responders who have prominent cellular IFN-γ production primarily driven by adaptive T cells, or tempered responders who skew toward antibody-mediated humoral immunity.

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Background: We assessed the impact of exposure to Plasmodium falciparum on parasite kinetics, clinical symptoms, and functional immunity after controlled human malaria infection (CHMI) in 2 cohorts with different levels of previous malarial exposure.

Methods: Nine adult males with high (sero-high) and 10 with low (sero-low) previous exposure received 3200 P. falciparum sporozoites (PfSPZ) of PfSPZ Challenge by direct venous inoculation and were followed for 35 days for parasitemia by thick blood smear (TBS) and quantitative polymerase chain reaction.

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Humoral immunity is a critical effector arm for protection against malaria but develops only slowly after repeated infections. T cell-mediated regulatory dynamics affect the development of antibody responses to parasites. Here, we hypothesize that T follicular helper cell (T) polarization generated by repeated asexual blood-stage infections delays the onset of protective humoral responses.

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Malaria remains a serious threat to global health. Sustained malaria control and, eventually, eradication will only be achieved with a broadly effective malaria vaccine. Yet a fundamental lack of knowledge about how antimalarial immunity is acquired has hindered vaccine development efforts to date.

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Dendritic cells are key linkers of innate and adaptive immunity. Efficient dendritic cell activation is central to the acquisition of immunity and the efficacy of vaccines. Understanding how dendritic cells are affected by blood-stage parasites will help to understand how immunity is acquired and maintained, and how vaccine responses may be impacted by malaria infection or exposure.

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Background: We investigated the poorly understood impact of declining malaria transmission on maintenance of antibodies to Plasmodium falciparum merozoite antigens and infected erythrocytes (IEs), including functional immunity.

Methods: In a 3-year longitudinal cohort of 300 Kenyan children, antibodies to different AMA1 and MSP2 alleles of merozoites, IE surface antigens, and antibody functional activities were quantified.

Results: Over a period in which malaria transmission declined markedly, AMA1 and MSP2 antibodies decreased substantially; estimated half-lives of antibody duration were 0.

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