Biology subjects

Daubenberger, C.

Publications and source records attributed to Daubenberger, C..

4 recordsLinked to original sources

bioRxiv2025

Dysfunctional memory B cell responses to the protective repeat region of the Plasmodium circumsporozoite protein are associated with waning humoral immunity

Malaria vaccines provide waning protection from disease that is correlated with the production of antibodies to the repeat region of the circumsporozoite protein (CSP). CSP-based vaccines display limited durability in malaria-naive individuals yet are even less effective in malaria-experienced individuals, suggesting the generation of non-optimal humoral immunity in response to both infection and vaccination. To address this hypothesis, we performed a cross-species, comprehensive analysis of B cell responses to CSP after Plasmodium infection or immunization, focusing our analysis on the repeat and C-terminus domains included in malaria subunit vaccines. Herein we demonstrate that the repetitive nature of the protective region of the CSP protein independently impacts the differentiation of the CSP-specific B cells, impinging on their ability to recall for multiple subsequent exposures.

immunology↗

bioRxiv2024

Regular Plasmodium falciparum importation onto Bioko Island, Equatorial Guinea, hampers malaria elimination from the island

The Bioko Island Malaria Elimination Project (BIMEP) has made significant progress in reducing the prevalence of Plasmodium falciparum on Bioko Island, Equatorial Guinea. However, like other malaria endemic islands like Sao Tome and Principe and Zanzibar, Tanzania, elimination efforts are hampered by imported infections. In an effort to understand the local transmission dynamics and the influence of importation on Bioko Islands P. falciparum population, whole-genome sequences were generated from field samples collected during the BIMEPs 2019 Malaria Indicator Survey (MIS). Within the sub-Saharan African context, we observed Bioko Island parasites did not significantly differentiate from nearby continental neighbors. Among Bioko infections, within-host diversity and the quantity of polyclonal infections appear similar to an area of moderate malaria transmission. However, we observed higher than expected genetic diversity among Bioko parasites, similar to high transmission areas, suggesting imported strains are contributing to transmission on the island. Among Biokos closest geographical neighbors, the flow of parasites with Bioko appeared more pronounced with the Gabonese parasite population, implying more importation may be coming from this region than others. Overall, despite significant investment in malaria control, results illustrate the challenges of eliminating malaria without both interrupting local transmission and accounting for importation from higher transmission areas, likely due to human migration. For there to be sustained progress towards elimination, the BIMEP needs, if feasible, to conduct targeted interventions of outgoing/incoming travelers, and ideally expand malaria control interventions to the continental region of Equatorial Guinea. ImportancePlasmodium falciparum accounts for the majority of malaria deaths globally, with over 500,000 estimated deaths in 2023, predominantly in sub-Saharan Africa, despite strong investment in control and elimination interventions. Incorporating sequencing technologies into malaria surveillance is viewed as a powerful tool to improve control strategies, including identifying parasite transmission pathways. Here, we provide the first genomic characterization of P. falciparum on Bioko Island and Equatorial Guinea since malaria control began in 2004, and use these data to better understand the contribution of neighboring regions to Biokos P. falciparum population. Results highlight the need to account for offisland contributors to transmission and to understand how unmitigated transmission in neighboring regions can hamper progress. This study furthers our understanding of how the flow of parasites between regions impacts infectious disease control and provides foundational genomic data in a previously undescribed region that can be used to inform malaria elimination efforts.

genomics↗

bioRxiv2021

Analysis of nucleic acids extracted from rapid diagnostic tests reveals a significant proportion of false positive test results associated with recent malaria treatment

Surveillance programs often use malaria rapid diagnostic tests (RDTs) to determine the proportion of the population carrying parasites in their peripheral blood to assess the malaria transmission intensity. Despite an increasing number of reports on false-negative and false-positive RDT results, there is a lack of systematic quality control activities for RDTs deployed in malaria surveillance programs. Our study provides a larger scale comparative evaluation of RDTs used in the 2018 Malaria Indicator Survey (MIS) conducted on Bioko Island, Equatorial Guinea. We conducted a molecular analysis by extraction of nucleic acids from 1,800 negative and 1,065 positive RDTs followed by qPCR analysis. These results were combined with a dataset collected in a comprehensive questionnaire from each MIS participant. Of the 2,865 RDTs that were collected in 2018 on Bioko Island and analysed in our study, 4.7% had a false-negative result. These false-negative RDT results were associated with low parasite density infections. In a substantial proportion of samples, we identified masked pfhrp2 and pfhrp3 gene deletions in which at least one P. falciparum strain carried a gene deletion. Among all positive RDTs analysed, 28.4% were tested negative by qPCR and therefore considered to be false-positive. Analysing the questionnaire data collected from the participants, this high proportion of false-positive RDT results could be explained by PfHRP2 antigen persistence after recent malaria treatment. We conclude that malaria surveillance depending solely on RDTs needs well-integrated quality control procedures assessing the extend and impact of reduced sensitivity and specificity of RDTs on malaria control programs.

microbiology↗

bioRxiv2019

Re-annotation of the Theileria parva genome refines 53% of the proteome and uncovers essential components of N-glycosylation, a conserved pathway in many organisms

BackgroundThe apicomplexan parasite Theileria parva causes a livestock disease called East coast fever (ECF), with millions of animals are at risk in sub-Saharan East and Southern Africa, the geographic distribution of T. parva. Over a million bovines die each year of ECF, with a tremendous economic burden to pastoralists in endemic countries. Comprehensive, accurate parasite genome annotation can facilitate the discovery of novel chemotherapeutic targets for disease treatment, as well as elucidate the biology of the parasite. However, genome annotation remains a significant challenge because of limitations in the quality and quantity of the data being used to inform the location and function of protein-coding genes and, when RNA data are used, the underlying biological complexity of the processes involved in gene expression. Here, we apply our recently published RNAseq dataset derived from the schizont life-cycle stage of T. parva to update structural and functional gene annotations across the entire nuclear genome. ResultsThe re-annotation effort lead to evidence-supported updates in over half of all protein-coding sequence (CDS) predictions, including exon changes, gene merges and gene splitting, an increase in average CDS length of approximately 50 base pairs, and the identification of 128 new genes. Among the new genes identified were those involved in N-glycosylation, a process previously thought not to exist in this organism and a potentially new chemotherapeutic target pathway for treating ECF. Alternatively-spliced genes were identified, and antisense and multi-gene family transcription were extensively characterized. ConclusionsThe process of re-annotation led to novel insights into the organization and expression profiles of protein-coding sequences in this parasite, and uncovered a minimal N-glycosylation pathway that changes our current understanding of the evolution of this post-translation modification in apicomplexan parasites.

genomics↗