Mathilde Hénaut, Julie Carbonneau, Inès Levade, Guy Boivin
{"title":"Fitness of SARS-CoV-2 Omicron subvariants in respiratory and gastrointestinal cell lines as determined by RT-ddPCR and whole genome sequencing","authors":"Mathilde Hénaut, Julie Carbonneau, Inès Levade, Guy Boivin","doi":"10.1093/infdis/jiae554","DOIUrl":"https://doi.org/10.1093/infdis/jiae554","url":null,"abstract":"The fitness of SARS-CoV-2 Omicron subvariants was determined in human epithelial and continuous cells of the respiratory and gastrointestinal tracts. Competition experiments over 4 days were performed followed by quantification of variant ratios by reverse transcription-droplet digital PCR. These quantitative data were correlated with whole genome sequencing. In competition experiments of two subvariants, the more recent XBB.1 subvariant outcompeted the BA.1.15 subvariant at early time points in the upper respiratory tract epithelium. No difference in replication was observed between the two subvariants in the lower respiratory tract. Furthermore, XBB.1 predominated over BA.1.15 and JN.1.1 subvariants in the gastrointestinal tract.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"62 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142596484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Johannes Schulte, Andreas Maurer, Lisa-Charlotte Domogalla, Nils Steinacker, Carolin Wadle, Johannes Kinzler, Matthias Eder, Constantin von zur Mühlen, Marvin Krohn-Grimberghe, Ann-Christin Eder
{"title":"2-[18F]F-p-aminobenzoic acid specifically detects infective endocarditis in positron emission tomography","authors":"Johannes Schulte, Andreas Maurer, Lisa-Charlotte Domogalla, Nils Steinacker, Carolin Wadle, Johannes Kinzler, Matthias Eder, Constantin von zur Mühlen, Marvin Krohn-Grimberghe, Ann-Christin Eder","doi":"10.1093/infdis/jiae547","DOIUrl":"https://doi.org/10.1093/infdis/jiae547","url":null,"abstract":"Background To the present day infective endocarditis (IE) represents a life-threatening disease with high mortality rate especially when caused by Staphylococcus aureus (S. aureus), the most common causative pathogen in this disease. Diagnosis of IE is based on clinical manifestations, pathogen detection by blood cultures and echocardiographic or other imaging findings. However, none of the methods used is capable of detecting the causative bacterial cells on the endothelium directly. Modern molecular imaging such as positron emission tomography/computed tomography (PET/CT) is playing an increasingly important role in unclear IE cases. This study focused on 2-[18F]F-p-aminobenzoic acid (2-[18F]F-PABA), a bacteria specific tracer for the diagnosis of IE using PET imaging for direct pathogen detection. Methods In vitro assays were performed to analyze 2-[18F]F-PABA uptake by S. aureus. For proof-of-concept in vivo trials an endocarditis mouse model was used to diagnose IE by PET/Magnetic resonance (MR) imaging. A subcutaneous abscess mouse model was supplemented to create larger bacterial vegetations for PET imaging. Results 2-[18F]F-PABA in vitro uptake by S. aureus was confirmed. Only living bacteria were able to accumulate the tracer while the extent of uptake varied between different S. aureus strains. In the in vivo proof-of-concept, IE was visualized in mice using 2-[18F]F-PABA-PET/MR imaging. Subsequently, 2-[18F]F-PABA specifically located S. aureus vegetations in the subcutaneous abscess model. Conclusions This study highlights the great potential of 2-[18F]F-PABA imaging for the direct detection of IE. Future studies might further investigate the clinical potential of this molecular imaging approach, finally aiming at a clinical implementation.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"196 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142596490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A M A M Winkel, E Kozanli, M E Haverkort, S M Euser, J G C Sluiter-Post, R Mariman, A Vogelzang, J de Bakker, C R Lap, M A van Houten, D Eggink, S F L van Lelyveld
{"title":"Lower levels of household transmission of SARS-CoV-2 VOC Omicron compared to Wild-type: an interplay between transmissibility and immune status","authors":"A M A M Winkel, E Kozanli, M E Haverkort, S M Euser, J G C Sluiter-Post, R Mariman, A Vogelzang, J de Bakker, C R Lap, M A van Houten, D Eggink, S F L van Lelyveld","doi":"10.1093/infdis/jiae546","DOIUrl":"https://doi.org/10.1093/infdis/jiae546","url":null,"abstract":"Background Knowledge of SARS-CoV-2 household transmission dynamics guides infection control and vaccination measures. This household cohort study prospectively assessed the impact of both the Omicron BA.2 variant and immunity on household transmission using dense saliva sampling and sequence analysis. Methods Households consisting of a PCR-confirmed index and at least two household members were enrolled in March and April 2022 during the Omicron BA.2 wave in the Netherlands. SARS-CoV-2 PCR was performed on ten consecutive saliva samples. Serum-antibodies were measured at baseline and day 42. Household and per-person Secondary Attack Rate (SAR) were calculated to measure transmission. Whole genome sequencing was performed for phylogenetic analysis, followed by sensitivity analysis, to correct for multiple household introductions and index definition. Results were compared with the identical, early-pandemic, pre-immunisation predecessor study. Results Sixty-seven households were included, consisting of 241 individuals (median age 33.0 years (IQR 12.0-46.0)). Maximum household SAR was 59.7%, per-person SAR 41.5%. Paediatric index cases were more likely to transmit. Transmission was negatively affected by household members’ immunity. Phylogenetic analysis showed multiple introductions in four households. Sensitivity analysis resulted in a minimal household SAR of 51.0% and per-person SAR of 28.5%. Conclusions The Omicron BA.2 variant is highly transmissible within households. However, the transmission rate is lower compared to previous studies with other SARS-CoV-2 variants, highlighting the effect of immunity. Regardless of immune status, children have a crucial role in Omicron household transmission. Intensive sampling and phylogenetic analysis are beneficial for correctly calculating transmission rates, especially during periods of minimal behavioural restrictions.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"244 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142596489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gesham Magombedze, Elena Vendrame, Devi SenGupta, Romas Geleziunas, Susan Little, Davey Smith, Bruce Walker, Jean-Pierre Routy, Frederick M Hecht, Tae-Wook Chun, Michael Sneller, Jonathan Z Li, Steven G Deeks, Michael J Peluso
{"title":"Early Viral Dynamics Predict HIV Post-Treatment Control After Analytic Treatment Interruption","authors":"Gesham Magombedze, Elena Vendrame, Devi SenGupta, Romas Geleziunas, Susan Little, Davey Smith, Bruce Walker, Jean-Pierre Routy, Frederick M Hecht, Tae-Wook Chun, Michael Sneller, Jonathan Z Li, Steven G Deeks, Michael J Peluso","doi":"10.1093/infdis/jiae551","DOIUrl":"https://doi.org/10.1093/infdis/jiae551","url":null,"abstract":"Background A key research priority for developing an HIV cure strategy is to define the viral dynamics and biomarkers associated with sustained post-treatment control. The ability to predict the likelihood of sustained post-treatment control or non-control could minimize the time off antiretroviral therapy (ART) for those destined to not control and anticipate longer periods off ART for those destined to control. Methods Mathematical modeling and machine learning were used to characterize virologic predictors of long-term virologic control using viral kinetics data from several studies in which participants interrupted ART. Predictors of post-ART outcomes were characterized using data accumulated from the time of treatment interruption, replicating real-time data collection in a clinical study, and classifying outcomes as either post-treatment control (plasma viremia ≤400 copies/mL at 2 of 3 time points for ≥24 weeks) or non-control. Results Potential predictors of virologic control were the time to rebound, the rate of initial rebound, and the peak plasma viremia. We found that people destined to be non-controllers could be identified within 3 weeks of rebound (prediction scores: accuracy, 80%; sensitivity, 82%; specificity, 71%). Conclusions Given the widespread use of analytic treatment interruption in cure-related trials, these predictors may be useful to increase the safety of analytic treatment interruption through the early identification of people who are unlikely to become post-treatment controllers.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142596716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mary G Slaughter, Samina Bhumbra, Kagan A Mellencamp, Ruth Namazzi, Robert O Opoka, Chandy C John
{"title":"Elevated levels of PDGF-BB and VEGF are associated with a decreased risk of readmission or death in children with severe malarial anemia","authors":"Mary G Slaughter, Samina Bhumbra, Kagan A Mellencamp, Ruth Namazzi, Robert O Opoka, Chandy C John","doi":"10.1093/infdis/jiae527","DOIUrl":"https://doi.org/10.1093/infdis/jiae527","url":null,"abstract":"Background Children with severe malarial anemia (SMA) typically have low in-hospital mortality but have a high risk of post-discharge readmission or death. We hypothesized that the dysregulation of hematopoiesis, vascular growth factors, and endothelial function that occurs in SMA might affect risk of readmission or death. Methods Plasma was obtained from children 18 months to 12 years old with SMA (N=145) in Kampala, Uganda on admission, and outcomes were assessed over 12-month follow-up. Admission plasma levels of ten biomarkers of vascular growth, hematopoiesis, and endothelial function were compared to risk of readmission or death over 12-month follow-up. Results Over 12-month follow-up, 19 of 145 children with SMA were either readmitted or died: 15 children were readmitted (13 with malaria) and 4 children died. In multivariable analyses adjusted for age and sex, elevated plasma levels of platelet-derived growth factor-BB (PDGF-BB) and vascular endothelial growth factor (VEGF) on admission were independently associated with a decreased risk of all-cause readmission or death (adjusted hazard ratios [95% confidence intervals], 0.28 [0.16-0.51] and 0.19 [0.08-0.48], respectively) and a decreased risk of readmission due to severe malaria (0.27 [0.15, 0.51] and 0.16 [0.05, 0.47]) but not with risk of uncomplicated malaria (1.01 [0.53, 1.95] and 2.07 [0.93-4.64]). Conclusions In children with severe malarial anemia, elevated plasma levels of PDGF-BB and VEGF, two factors that promote angiogenesis, are associated with a decreased risk of readmission or death in the year following admission, primarily driven by a decrease in the risk of recurrent severe malaria.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"60 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142490536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jing Bi, Qinglong Guo, Yaqi Gong, Xi Chen, Haojia Wu, Li Song, Yating Xu, Min Ou, Zhaoqin Wang, Jiean Chen, Chenran Jiang, Aimei Liu, Guobao Li, Guoliang Zhang
{"title":"Troglitazone reduces intracellular Mycobacterium tuberculosis survival via macrophage autophagy through LKB1-AMPKα signaling","authors":"Jing Bi, Qinglong Guo, Yaqi Gong, Xi Chen, Haojia Wu, Li Song, Yating Xu, Min Ou, Zhaoqin Wang, Jiean Chen, Chenran Jiang, Aimei Liu, Guobao Li, Guoliang Zhang","doi":"10.1093/infdis/jiae523","DOIUrl":"https://doi.org/10.1093/infdis/jiae523","url":null,"abstract":"Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb), results in significant morbidity and mortality worldwide. Host-directed therapy (HDT), including conventional drugs, is a promising anti-TB strategy that shows synergistic antibacterial effects when combined with anti-TB drugs. Here, the mycobactericidal effect of three anti-diabetic drugs was examined. Of these, only Troglitazone (Trog) enhanced the antimycobacterial effect in vitro and in vivo. This was due to Trog-mediated autophagy activation. Moreover, a knock-down experiment revealed that Trog activated autophagy and exhibited antimycobacterial activity through the LKB1-AMPK signaling pathway. Molecular docking and co-immunoprecipitation experiments demonstrated that Trog promoted LKB1 phosphorylation and activation by targeting STRADA. Finally, we found that Trog inhibited the intracellular survival of clinical isoniazid (INH)-resistant Mtb, and the combination of Trog and INH showed additive antibacterial effects against Mtb H37Rv. Taken together, anti-diabetic Trog may be repurposed as an HDT candidate and combined with first-line anti-TB drugs.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"60 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142490445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Keon-Woong Yoon, Ki Back Chu, Gi-Deok Eom, Jie Mao, Eun-Kyung Moon, Sung Soo Kim, Fu-Shi Quan
{"title":"CpG-adjuvanted virus-like particle vaccine induces protective immunity against Leishmania donovani infection","authors":"Keon-Woong Yoon, Ki Back Chu, Gi-Deok Eom, Jie Mao, Eun-Kyung Moon, Sung Soo Kim, Fu-Shi Quan","doi":"10.1093/infdis/jiae526","DOIUrl":"https://doi.org/10.1093/infdis/jiae526","url":null,"abstract":"Visceral leishmaniasis (VL) poses a significant public health challenge due to the lack of an approved human vaccine. We attempted to enhance the efficacy of virus-like particle vaccines expressing the Leishmania donovani promastigote surface antigen (LdPSA-VLP) by adjuvanting with CpG oligodeoxynucleotide (CpG-ODN). Here, adjuvanted vaccine-induced immune responses and their efficacies in mice challenged with mCherry-expressing L. donovani promastigotes were evaluated. Adjuvanted LdPSA-VLP vaccination significantly elevated parasite-specific IgG, IgG1, IgG2a, and IgG2b serum antibody levels. Additionally, vaccinated mice exhibited enhanced germinal center B cells and splenic T cell activities, compared to unimmunized mice. Importantly, adjuvanted LdPSA-VLPs reduced the levels of inflammatory cytokines IFN-γ and IL-6 in visceral organs, leading to decreased total parasite burden and protection against L. donovani challenge. Our findings indicate that CpG-ODN enhanced the protection conferred by LdPSA-VLPs, offering a promising step toward effective VL vaccine development.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"110 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Isabel Leroux-Roels, Azhar Alhatemi, Magalie Caubet, Fien De Boever, Bertrand de Wergifosse, Mohamed El Idrissi, Guilherme S Ferreira, Bart Jacobs, Axel Lambert, Sandra Morel, Charlotte Servais, Juan Pablo Yarzabal
{"title":"Safety and Immunogenicity of an Adjuvanted Clostridioides difficile Vaccine Candidate in Healthy Adults: A Randomized Placebo-Controlled Phase 1 Study","authors":"Isabel Leroux-Roels, Azhar Alhatemi, Magalie Caubet, Fien De Boever, Bertrand de Wergifosse, Mohamed El Idrissi, Guilherme S Ferreira, Bart Jacobs, Axel Lambert, Sandra Morel, Charlotte Servais, Juan Pablo Yarzabal","doi":"10.1093/infdis/jiae466","DOIUrl":"https://doi.org/10.1093/infdis/jiae466","url":null,"abstract":"Background This study investigated the safety, reactogenicity, and immunogenicity in healthy subjects of a Clostridioides difficile vaccine candidate with/without adjuvant, targeting toxins A and B. Methods In this first-in-human, phase 1, observer-blind study, subjects aged 18–45 years were randomized to receive F2 antigen (n = 10) or placebo (n = 10), and subjects aged 50–70 years to receive F2 antigen plus AS01 adjuvant (n = 45), F2 antigen (n = 45), or placebo (n = 30) in 2 doses 1 month apart. A subcohort (n = 40) received a third dose 15 months later. Solicited adverse events (AEs) were recorded for 7 days and unsolicited AEs for 30 days after each dose. Immunogenicity was assessed at baseline and after each dose. Results Solicited AEs were transient and most frequent in subjects receiving F2 antigen plus AS01. No serious AEs were considered related to study vaccine. Immunogenicity was substantially higher in subjects receiving F2 antigen plus AS01 than subjects receiving F2 antigen alone. A third dose increased the immune response in subjects with baseline neutralization titers below the assay lower limit of quantitation. Conclusions The GSK C. difficile vaccine candidate was immunogenic, especially when given with AS01, and was well tolerated with an acceptable safety profile. Clinical Trial Registration NCT04026009.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"An Expression Quantitative Trait Locus of Fc Gamma Receptor Genes is Associated with Anti-Malarial IgG Responses and Infection Levels in Burkinabe Families","authors":"Christelle Dieppois, Mathieu Adjemout, Jules Cretin, Frederic Gallardo, Magali Torres, Christophe Picard, Serge Aimé Sawadogo, Pascal Rihet, Pascale Paul","doi":"10.1093/infdis/jiae528","DOIUrl":"https://doi.org/10.1093/infdis/jiae528","url":null,"abstract":"Background The interaction between antibodies and Fc gamma receptors (FcγRs) plays a critical role in regulating immune responses to Plasmodium falciparum. Polymorphisms in genes encoding FcγRs influence the host's capacity to control parasite infection. This study investigates whether non-coding variants influencing FcγR expression are associated with anti-malarial immunization and infection traits. Methods We utilized eQTL databases and functional annotations to identify non-coding variants, specifically rs1771575, rs2099684, and rs6700241, within the FCGR gene cluster. In addition, we examined the coding variants rs1801274 (p.His167Arg) and rs1050501 (p.Ile231Thr), which affect the affinity of FcγRIIa and FcγRIIb for IgG. These variants were genotyped in 163 individuals from Burkinabe families. Family-based linear mixed regression and Quantitative Transmission Disequilibrium Tests (QTDT) analyses were performed to assess associations with IgG levels and malaria infection, accounting for relevant covariates. Results Linear mixed models identified rs1771575 as associated with total IgG levels, while both rs1771575 and rs1801274 were linked to IgG2, and rs1050501 to IgG1 levels. A haplotype combining rs2099684 and rs6700241 was positively associated with IgG1. The rs1771575-CC and rs1050501-TT genotypes correlated with higher infection levels in children. QTDT models confirmed the association of rs1771575 with IgG2 and infection in children. Conclusions Our findings suggest that the intergenic variant rs1771575 serves as an independent marker for IgG levels and blood infection in children. This highlights the interplay between regulatory variants and coding mutations in FCGR, which may influence immune function and antibody production. These results underscore the potential for personalized strategies to monitor humoral responses in malaria-endemic regions.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"54 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142490543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marie Høst Pahus,Yu Zheng,Maxine Olefsky,Jesper Damsgaard Gunst,Pablo Tebas,Babafemi Taiwo,Ole S Søgaard,Michael J Peluso,Yolanda Lie,Jacqueline D Reeves,Christos J Petropoulos,Marina Caskey,Katharine J Bar
{"title":"Evaluation and real-world experience of a neutralization susceptibility screening assay for broadly neutralizing anti-HIV-1 antibodies.","authors":"Marie Høst Pahus,Yu Zheng,Maxine Olefsky,Jesper Damsgaard Gunst,Pablo Tebas,Babafemi Taiwo,Ole S Søgaard,Michael J Peluso,Yolanda Lie,Jacqueline D Reeves,Christos J Petropoulos,Marina Caskey,Katharine J Bar","doi":"10.1093/infdis/jiae486","DOIUrl":"https://doi.org/10.1093/infdis/jiae486","url":null,"abstract":"BACKGROUNDDevelopment of a screening assay for the clinical use of broadly neutralizing antibodies (bnAbs) is a priority for HIV therapy and cure initiatives.METHODSWe assessed the PhenoSense Monoclonal Antibody (mAb) Assay (Labcorp-Monogram Biosciences) which is CLIA-validated and has been used prospectively and retrospectively in multiple recent bnAb clinical trials.RESULTSWhen performed on pre-ART plasma and on-ART longitudinal PBMC samples sourced from a recent clinical trial, the PhenoSense mAb Assay produced robust reproducibility, concordance across sample types, and expected ranges in the susceptibility measures of bnAbs in clinical development. PhenoSense mAb applied retrospectively to baseline samples from three recent studies correlated with published laboratory-based study evaluations, but baseline bnAb susceptibility was not consistently predictive of durable virus suppression. Assessment of the feasibility of the assay in four recent clinical studies provides estimates of assay success rate and processing time.CONCLUSIONSThe PhenoSense mAb Assay provides reproducible bnAb susceptibility measurements across relevant sample types yet was not consistently predictive of virus suppression. Logistical and operational assay requirements can impact timely clinical trial conduct. These results inform bnAb studies in development.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"194 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142488190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}