Browsing by Author "Narum, David L."

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    Antibody correlates of risk of clinical malaria in an area of low and unstable malaria transmission in western Kenya
    (Springer Nature, 2025-03-04) Odhiambo, Eliud O.; Mellencamp, Kagan A.; Ondigo, Bartholomew N.; Hamre, Karen E. S.; Beeson, James G.; Opi, D. Herbert; Narum, David L.; Ayodo, George; John, Chandy C.; Microbiology and Immunology, School of Medicine
    Background: Defining antibody correlates of protection against clinical malaria in areas of low and unstable transmission is challenging because of limited malaria cases in these areas. Additionally, clinical malaria affects both adults and children in areas of low and unstable transmission, but it is unclear whether antibody correlates of protection against malaria differ with age. Methods: Blood samples were obtained from 5753 individuals in Kenyan highland area with low and seasonal malaria transmission in 2007 and recorded episodes of clinical malaria in this population from 2007 to 2017. Using a nested case-control study design, participants who developed clinical malaria (cases) were matched by age and village to those who did not (controls). Immunoglobulin (Ig)G, IgG1, IgG3, IgA and IgM responses to 16 Plasmodium falciparum antigens were compared in individuals < 5 years old (80 cases vs. 240 controls), 5-14 years old (103 cases vs. 309 controls) and ≥ 15 years old (118 cases vs. 354 controls). Antibody level was correlated with risk of clinical malaria, adjusted for malaria exposure markers. Results: In all age groups, most antibodies were not associated with risk of clinical malaria. In children < 5 years, higher levels of IgG to GLURP-R2 and MSP-2, IgG1 to GLURP-R2, and IgG3 to MSP-2 were associated with reduced risk of clinical malaria, while higher IgG3 levels to CSP were associated with increased risk of clinical malaria. In children 5-14 years and individuals ≥ 15 years, higher antibody levels to multiple P. falciparum antigens were associated with an increased risk of clinical malaria, and none were associated with decreased risk of clinical malaria. Conclusions: Antibody correlates of protection against clinical malaria were observed only in children < 5 years old in this area of low and unstable malaria transmission. In older children and adults in this area, some antibody responses correlated with increased risk of clinical malaria. Future studies in low malaria transmission areas should evaluate the comparative contributions of cellular and humoral immunity to protection from clinical malaria in young children versus older children and adults.
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    Decrease in Numbers of Naive and Resting B Cells in HIV-Infected Kenyan Adults Leads to a Proportional Increase in Total and Plasmodium falciparum-Specific Atypical Memory B Cells
    (American Association of Immunologists, 2017-06-15) Frosch, Anne E.; Odumade, Oludare A.; Taylor, Justin J.; Ireland, Kathleen; Ayodo, George; Ondigo, Bartholomew; Narum, David L.; Vulule, John; John, Chandy C.; Medicine, School of Medicine
    Human immunodeficiency virus type 1 (HIV-1) infection is associated with B cell activation and exhaustion, and hypergammaglobulinemia. How these changes influence B cell responses to coinfections such as malaria is poorly understood. To address this, we compared B cell phenotypes and Abs specific for the Plasmodium falciparum vaccine candidate apical membrane Ag-1 (AMA1) in HIV-infected and uninfected adults living in Kenya. Surprisingly, HIV-1 infection was not associated with a difference in serum AMA1-specific Ab levels. HIV-infected individuals had a higher proportion of total atypical and total activated memory B cells (MBCs). Using an AMA1 tetramer to detect AMA1-specific B cells, HIV-infected individuals were also shown to have a higher proportion of AMA1-specific atypical MBCs. However, this proportional increase resulted in large part from a loss in the number of naive and resting MBCs rather than an increase in the number of atypical and activated cells. The loss of resting MBCs and naive B cells was mirrored in a population of cells specific for an Ag to which these individuals were unlikely to have been chronically exposed. Together, the data show that changes in P. falciparum Ag-specific B cell subsets in HIV-infected individuals mirror those in the overall B cell population, and suggest that the increased proportion of atypical MBC phenotypes found in HIV-1-infected individuals results from the loss of naive and resting MBCs.
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    Protein-Specific Features Associated with Variability in Human Antibody Responses to Plasmodium falciparum Malaria Antigens
    (American Society of Tropical Medicine and Hygiene, 2018-01) Liu, Eugene W.; Skinner, Jeff; Tran, Tuan M.; Kumar, Krishan; Narum, David L.; Jain, Aarti; Ongoiba, Aissata ba; Traoré, Boubacar; Felgner, Philip L.; Crompton, Peter D.; Medicine, School of Medicine
    The magnitude of antibody responses varies across the individual proteins that constitute any given microorganism, both in the context of natural infection and vaccination with attenuated or inactivated pathogens. The protein-specific factors underlying this variability are poorly understood. In 267 individuals exposed to intense seasonal malaria, we examined the relationship between immunoglobulin G (IgG) responses to 861 Plasmodium falciparum proteins and specific features of these proteins, including their subcellular location, relative abundance, degree of polymorphism, and whether they are predicted to have human orthologs. We found that IgG reactivity was significantly higher to extracellular and plasma membrane proteins and also correlated positively with both protein abundance and degree of protein polymorphism. Conversely, IgG reactivity was significantly lower to proteins predicted to have human orthologs. These findings provide insight into protein-specific factors that are associated with variability in the magnitude of antibody responses to natural P. falciparum infection-data that could inform vaccine strategies to optimize antibody-mediated immunity as well as the selection of antigens for sero-diagnostic purposes.