Biology subjects

Proietti, C.

Publications and source records attributed to Proietti, C..

3 recordsLinked to original sources

bioRxiv2024

Differential EBV protein-specific antibody response between responders and non-responders to EBVSTs immunotherapy

Epstein-Barr virus (EBV) is associated with a diverse range of lymphomas. EBV-specific T-cell (EBVST) immunotherapies have shown promise in safety and clinical effectiveness in treating EBV-associated lymphomas, but not all patients respond to treatment. To identify the set of EBV-directed antibody responses associated with clinical response in patients with EBV-associated lymphomas, we comprehensively characterized the immune response to the complete EBV proteome using a custom protein microarray in 56 EBV-associated lymphoma patients who were treated with EBVST infusions enrolled in Phase I clinical trials. Significant differences in antibody profiles between responders and non-responders emerged at 3 months post-EBVST infusion. Twenty-five IgG antibodies were present at significantly higher levels in non-responders compared to responders at 3 months post-EBVST infusion, and 10 of these IgG antibody associations remained after adjustment for sex, age, and cancer diagnosis type. Random forest prediction analysis further confirmed that these 10 antibodies were important for predicting clinical response. Differential IgG antibody responses were directed against LMP2A (four fragments), BGRF1/BDRF1 (two fragments), LMP1, BKRF2, BKRF4, and BALF5. Paired analyses using blood samples collected at both pre-infusion and 3 months post-EBVST infusion indicated an increase in the mean antibody level for six other anti-EBV antibodies (IgG: BGLF2, LF1, BGLF3; IgA: BGLF3, BALF2, BBLF2/3) in non-responders. Overall, our results indicate that EBV-directed antibodies can be biomarkers for predicting the clinical response of individuals with EBV-associated lymphomas treated with EBVST infusions.

microbiology↗

bioRxiv2018

Development and validation of serological markers for detecting recent exposure to Plasmodium vivax infection

In order to accelerate towards malaria elimination, improved targeting of limited resources is essential. A major gap in our elimination toolkit for Plasmodium vivax malaria is the identification of individuals carrying arrested liver stages, called hypnozoites. These clinically silent but frequently relapsing hypnozoites are key to P. vivax persistence. Whilst hypnozoites cannot be directly detected, individuals who have had recent exposure to P. vivax and have not been treated are likely to harbor these parasites. By measuring IgG antibody responses to over 300 P. vivax proteins, a panel of serological markers capable of detecting exposure to P. vivax infections in the prior 9-month period was identified and validated. Using antibody responses to 8 P. vivax proteins, 80% sensitivity and specificity for detecting recent infections were achieved in three independent studies conducted in Thailand, Brazil and the Solomon Islands. As these individuals have a high likelihood of harboring hypnozoites, the suite of these 8 antibody responses can serve as biomarkers for the identification of individuals who should be targeted for treatment with liver-stage drugs such as primaquine and tafenoquine in mass drug administration programs aimed at controlling and eliminating P. vivax malaria.\n\nOne Sentence SummaryThe manuscript describes identification and validation of a novel panel of P. vivax proteins that can be used to detect recent exposure to P. vivax infections within the prior 9 months.

microbiology↗

bioRxiv2018

Protective immunity against severe malaria is associated with antibodies to a conserved repertoire of PfEMP1 variants

Extreme diversity of the major surface antigen and virulence determinant of the malaria parasite Plasmodium falciparum, Erythrocyte Membrane Protein-1 (PfEMP1), poses a major barrier to identifying targets of protective immunity. To overcome this problem, we developed a PfEMP1 protein microarray containing 456 DBL domains, which was used to characterize the immunome of a cohort of semi-immune children and to identify variants associated with protective immune responses. Children with high mean antibody levels to DBL group 2 had a 26-36% reduced risk of uncomplicated (clinical) malaria, however only 8 diverse DBL variants were weakly associated with protection from clinical malaria and had low predictive accuracy. On the other hand, children with high mean antibodies to DBL groups 1 and 2 (which are markers for pathogenic \"Type A\" PfEMP1) and elevated antibodies to 85 (18.6%) of individual DBL variants had a 70 -100% reduced risk of severe malaria. Of the top 20 predictive variants for severe disease protection, 17 were strongly associated with protection (86 - 100% reduction in risk of severe malaria) and had high predictive accuracy for severe disease risk. Many variants were conserved and had highly correlated antibody responses, including the three highest-ranking variants, which were linked to EPCR-binding CIDR domains. The results suggest that while immunity to uncomplicated malaria is characterised by antibodies to a diverse repertoire of PfEMP1, immunity to severe malaria requires antibodies to a limited subset of antigenically conserved variants. These findings provide new insights into antimalarial immunity and potential biomarkers for tracking disease risk.

microbiology↗