Carla Proietti

Australian Institute of Tropical Health and Medicine

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Denise L. Doolan

Australian Institute of Tropical Health and Medicine

Anna E. Coghill

Moffitt Cancer Center

Zhiwei Liu

Division of Cancer Epidemiology and Genetics

Allan Hildesheim

Division of Cancer Epidemiology and Genetics

Kelly J. Yu

National Cancer Institute

Ruth M. Pfeiffer

Division of Cancer Epidemiology and Genetics

Cheng‐Ping Wang

National Taiwan University Hospital

Wan‐Lun Hsu

Fu Jen Catholic University

Pei‐Jen Lou

National Taiwan University Hospital

Yin-Chu Chien

Genomics Research Center, Academia Sinica

Cooperative Institutions

Universitas Gadjah Mada

National Institutes of Health

National Cancer Institute

University of Hong Kong

Sapienza University of Rome

London School of Hygiene & Tropical Medicine

Sun Yat-sen University

Australian Institute of Tropical Health and Medicine

James Cook University

Chinese University of Hong Kong

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Plasmodium malariae and Plasmodium ovale infections and their association with common red blood cell polymorphisms in a highly endemic area of Uganda

Transactions of the Royal Society of Tropical Medicine and Hygiene (2019)

Lorenzo Subissi Bernard N. Kanoi Betty Balikagala Thomas G. Egwang Mary C. Oguike

Plasmodium ovale and Plasmodium malariae infections are scarcely studied in sub-Saharan Africa, where the Plasmodium falciparum species predominates. The objective of this study is to investigate the prevalence of P. ovale and P. malariae infections and their relationship with common red blood cell polymorphisms in a cohort of 509 individuals from Uganda.Three cross-sectional surveys were conducted in individuals of 1-10 and >20 y of age from the Apac district at baseline and 6 and 16 weeks after drug treatment. Malaria infections were assessed by polymerase chain reaction and genotyping was performed for the sickle-cell allele, α-thalassaemia and glucose-6-phosphate dehydrogenase.At baseline, the prevalence of infection was 7.5%, 12.6% and 57.4% for P. ovale, P. malariae and P. falciparum species, respectively. Co-infections were present in 14.1% of individuals, all including P. falciparum parasites. In children 1-5 y of age, the prevalence of P. ovale mono-infections increased significantly from 1.7% to 7.3% over time (p=0.004) while the prevalence of P. malariae and P. falciparum infections declined significantly during this study. After adjusting for confounding and multiple testing, only α-thalassaemia had a statistically significant increase in the odds of P. falciparum infections (odds ratio 1.93 [95% confidence interval 1.26 to 2.94]).Common red blood cell polymorphisms do not show strong effects on mild Plasmodium infections in this Ugandan population. To understand the extent of this result, similar studies should be carried out in other populations using larger cohorts.

Plasmodium ovale

Plasmodium malariae

10.1093/trstmh/trz015

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Citations (3)

Supplementary Table S1 from Comparative Analysis of the Humoral Immune Response to the EBV Proteome across EBV-Related Malignancies

Ilona Argirion Ruth M. Pfeiffer Carla Proietti Anna E. Coghill Kelly J. Yu

Supplementary Table S1 shows marker pathway allocation and corresponding citations

Proteome

Table (database)

10.1158/1055-9965.22724999

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Supplementary Table S3 from Comparative Analysis of the Humoral Immune Response to the EBV Proteome across EBV-Related Malignancies

Ilona Argirion Ruth M. Pfeiffer Carla Proietti Anna E. Coghill Kelly J. Yu

Supplementary Table S3 shows positivity rates of the 46 individual markers among cases and controls in each study

Proteome

Table (database)

10.1158/1055-9965.22724993.v1

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Dissecting T cell or antibody immunodominance in a complex host-pathogen system

Malaria Journal (2012)

Carla Proietti Lutz Krause Joanne S. Roddick Angela Trieu Denise L. Doolan

Background Vaccines are considered the most cost-effective public health measure for the prevention of infectious diseases, with many demonstrated successes. However the Plasmodium parasite, causative agent of malaria, has eluded decades of efforts aimed at developing an effective intervention. Contributing to this is the complexity of the parasite life cycle and our poor understanding of the mechanisms and antigenic targets of host immunity to the parasite.

Immunodominance

10.1186/1475-2875-11-s1-o23

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Citations (3)

Influence of infection on malaria‐specific antibody dynamics in a cohort exposed to intense malaria transmission in northern Uganda

Parasite Immunology (2013)

Carla Proietti Federica Verra M. Bretscher William J. Stone Bernard N. Kanoi

Summary The role of submicroscopic infections in modulating malaria antibody responses is poorly understood and requires longitudinal studies. A cohort of 249 children ≤5 years of age, 126 children between 6 and 10 years and 134 adults ≥20 years was recruited in an area of intense malaria transmission in A pac, U ganda and treated with artemether/lumefantrine at enrolment. Parasite carriage was determined at enrolment and after 6 and 16 weeks using microscopy and PCR . Antibody prevalence and titres to circumsporozoite protein, apical membrane antigen‐1 ( AMA ‐1), merozoite surface protein‐1 ( MSP ‐1 19 ), merozoite surface protein‐2 ( MSP ‐2) and A nopheles gambiae salivary gland protein 6 (g SG 6) were determined by ELISA . P lasmodium falciparum infections were detected in 38·1% (194/509) of the individuals by microscopy and in 57·1% (284/493) of the individuals by PCR at enrolment. Antibody prevalence and titre against AMA ‐1, MSP ‐1 19 , MSP ‐2 and g SG 6 were related to concurrent (sub‐)microscopic parasitaemia. Responses were stable in children who were continuously infected with malaria parasites but declined in children who were never parasitaemic during the study or were not re‐infected after treatment. These findings indicate that continued malaria infections are required to maintain antibody titres in an area of intense malaria transmission.

Circumsporozoite protein

Merozoite surface protein

Artemether/lumefantrine

10.1111/pim.12031

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Citations (41)

The case for a rational genome-based vaccine against malaria

Frontiers in Microbiology (2015)

Carla Proietti Denise L. Doolan

Historically, vaccines have been designed to mimic the immunity induced by natural exposure to the target pathogen, but this approach has not been effective for any parasitic pathogens of humans or complex pathogens that cause chronic disease in humans, such as Plasmodium. Despite intense efforts by many laboratories around the world on different aspects of Plasmodium spp. molecular and cell biology, epidemiology and immunology, progress towards the goal of an effective malaria vaccine has been disappointing. The premise of rational vaccine design is to induce the desired immune response against the key pathogen antigens or epitopes targeted by protective immune responses. We advocate that development of an optimally efficacious malaria vaccine will need to improve on nature, and that this can be accomplished by rational vaccine design facilitated by mining genomic, proteomic and transcriptomic datasets in the context of relevant biological function. In our opinion, modern genome-based rational vaccine design offers enormous potential above and beyond that of whole-organism vaccines approaches established over 200 years ago where immunity is likely suboptimal due to the many genetic and immunological host-parasite adaptations evolved to allow the Plasmodium parasite to coexist in the human host, and which are associated with logistic and regulatory hurdles for production and delivery.

Plasmodium (life cycle)

10.3389/fmicb.2014.00741

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Citations (25)

Genome-based vaccine design: the promise for malaria and other infectious diseases

International Journal for Parasitology (2014)

Denise L. Doolan Simon H. Apte Carla Proietti

Vaccines are one of the most effective interventions to improve public health, however, the generation of highly effective vaccines for many diseases has remained difficult. Three chronic diseases that characterise these difficulties include malaria, tuberculosis and HIV, and they alone account for half of the global infectious disease burden. The whole organism vaccine approach pioneered by Jenner in 1796 and refined by Pasteur in 1857 with the "isolate, inactivate and inject" paradigm has proved highly successful for many viral and bacterial pathogens causing acute disease but has failed with respect to malaria, tuberculosis and HIV as well as many other diseases. A significant advance of the past decade has been the elucidation of the genomes, proteomes and transcriptomes of many pathogens. This information provides the foundation for new 21st Century approaches to identify target antigens for the development of vaccines, drugs and diagnostic tests. Innovative genome-based vaccine strategies have shown potential for a number of challenging pathogens, including malaria. We advocate that genome-based rational vaccine design will overcome the problem of poorly immunogenic, poorly protective vaccines that has plagued vaccine developers for many years.

10.1016/j.ijpara.2014.07.010

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A novel population of memory‐activated natural killer cells associated with low parasitaemia in Plasmodium falciparum‐exposed sickle‐cell trait children

Clinical & Translational Immunology (2020)

Claire Loiseau Ogobara K. Doumbo Boubacar Traoré Jamie L. Brady Carla Proietti

The sickle-cell trait phenotype is associated with protection from malaria. Multiple molecular mechanisms have been proposed to explain this protection, but the role of the host immune system has been poorly investigated. We hypothesised that cellular immunity to malaria may develop differently in sickle-cell trait children (HbAS) and children with normal haemoglobin (HbAA) repeatedly exposed to Plasmodium falciparum (Pf).Paired samples collected prior to the Pf transmission season and during the first malaria episode of the ensuing transmission season from HbAS and HbAA children were analysed by multiplex bead-based assay and comprehensive multi-dimensional flow cytometry profiling.Cellular immune profiles were enriched in HbAS relative to HbAA children before the start of the Pf transmission season, with a distinct NK subset. These cells were identified as a novel subset of memory-activated NK cells characterised by reduced expression of the ecto-enzyme CD38 as well as co-expression of high levels of HLA-DR and CD45RO. The frequency of this NK subset before the transmission season was negatively correlated with parasite density quantified during the first malaria episode of the ensuing transmission season. Functional assessment revealed that these CD38dim CD45RO+ HLA-DR+ NK cells represent a important source of IFN-γ.Our data suggest that this novel memory-activated NK cell subset may contribute to an accelerated and enhanced IFN-γ-mediated immune response and to control of parasite density in individuals with the sickle-cell trait. This distinct cellular immune profile may contribute to predispose HbAS children to a relative protection from malaria.

Sickle cell trait

Mass cytometry

10.1002/cti2.1125

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The Effect of Tropical Temperatures on the Quality of RNA Extracted from Stabilized Whole-Blood Samples

International Journal of Molecular Sciences (2022)

Yomani D. Sarathkumara Daniel J. Browne Ashton M. Kelly David J. Pattinson C. M. Rush

Whole-blood-derived transcriptional profiling is widely used in biomarker discovery, immunological research, and therapeutic development. Traditional molecular and high-throughput transcriptomic platforms, including molecular assays with quantitative PCR (qPCR) and RNA-sequencing (RNA-seq), are dependent upon high-quality and intact RNA. However, collecting high-quality RNA from field studies in remote tropical locations can be challenging due to resource restrictions and logistics of post-collection processing. The current study tested the relative performance of the two most widely used whole-blood RNA collection systems, PAXgene® and Tempus™, in optimal laboratory conditions as well as suboptimal conditions in tropical field sites, including the effects of extended storage times and high storage temperatures. We found that Tempus™ tubes maintained a slightly higher RNA quantity and integrity relative to PAXgene® tubes at suboptimal tropical conditions. Both PAXgene® and Tempus™ tubes gave similar RNA purity (A260/A280). Additionally, Tempus™ tubes preferentially maintained the stability of mRNA transcripts for two reference genes tested, Succinate dehydrogenase complex, subunit A (SDHA) and TATA-box-binding protein (TBP), even when RNA quality decreased with storage length and temperature. Both tube types preserved the rRNA transcript 18S ribosomal RNA (18S) equally. Our results suggest that Tempus™ blood RNA collection tubes are preferable to PAXgene® for whole-blood collection in suboptimal tropical conditions for RNA-based studies in resource-limited settings.

TEMPUS

10.3390/ijms231810609

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Citations (6)

Supplemental Methods from Identification of a Novel, EBV-Based Antibody Risk Stratification Signature for Early Detection of Nasopharyngeal Carcinoma in Taiwan

Anna E. Coghill Ruth M. Pfeiffer Carla Proietti Wan‐Lun Hsu Yin-Chu Chien

Supplemental Methods

Risk Stratification

Signature (topology)

Identification

Stratification (seeds)

10.1158/1078-0432.22461585.v1

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