Pathogens and Immunity最新文献

{"title":"Effect of Ceftaroline, Ceftazidime/Avibactam, Ceftolozane/Tazobactam, and Meropenem/Vaborbactam on Establishment of Colonization by Vancomycin-Resistant Enterococci and <i>Klebsiella pneumoniae</i> in Mice.","authors":"Bryan S Hausman, Samir Memic, Jennifer L Cadnum, Elizabeth G Zink, Brigid M Wilson, Curtis J Donskey","doi":"10.20411/pai.v9i2.711","DOIUrl":"https://doi.org/10.20411/pai.v9i2.711","url":null,"abstract":"<p><strong>Background: </strong>The potential for promotion of intestinal colonization with healthcare-associated pathogens by new antibiotics used to treat infections due to multidrug-resistant Gram-negative bacilli is unclear.</p><p><strong>Methods: </strong>Mice treated for 3 days with daily subcutaneous phosphate-buffered saline (control), ceftazidime/avibactam, ceftolozane/tazobactam, ceftaroline, and meropenem/vaborbactam were challenged with 10,000 colony-forming units (CFU) of vancomycin-resistant <i>Enterococcus</i> (VRE) resistant to each of the antibioics or carbapenemase-producing <i>Klebsiella pneumoniae</i> 1 day after the final treatment dose. The concentrations of VRE or <i>K. pneumoniae</i> in stool were measured on days 1, 3, 6, and 15 after challenge.</p><p><strong>Results: </strong>Control mice had transient low levels of VRE or <i>K. pneumoniae</i> (<3 log₁₀ CFU/g) detected in stool with negative cultures on days 6 and 15 after challenge. In comparison to control mice, each of the antibiotics promoted establishment of high-density colonization with VRE (mean concentration, >8 log₁₀ CFU/g of stool on day 1 after challenge) that persisted at >4 log₁₀ CFU/g of stool through day 15 (<i>P</i><0.01). In comparison to control mice, meropenem/vaborbactam and ceftaroline promoted high-density colonization with <i>K. pneumoniae</i> (peak concentration, >8 log₁₀ CFU/g of stool) (<i>P</i><0.01), ceftolozane/tazobactam promoted colonization to a lesser degree (peak concentration, >5 log₁₀ CFU/g of stool), and ceftazidime/avibactam did not promote colonization (<i>P</i>>0.05).</p><p><strong>Conclusions: </strong>Our results suggest that several beta-lactam antibiotics recently developed for treatment of infections with resistant Gram-negative bacilli have the potential to promote colonization by healthcare-associated pathogens. Additional studies are needed to examine the impact of these agents in patients.</p>","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"9 2","pages":"194-204"},"PeriodicalIF":0.0,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11432534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142355748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"People Living With HIV Have More Intact HIV DNA in Circulating CD4+ T Cells if They Have History of Pulmonary Tuberculosis.","authors":"Marc Antoine Jean Juste, Yvetot Joseph, Dominique Lespinasse, Alexandra Apollon, Parmida Jamshidi, Myung Hee Lee, Maureen Ward, Esther Brill, Yanique Duffus, Uche Chukwukere, Ali Danesh, Winiffer Conce Alberto, Daniel W Fitzgerald, Jean W Pape, R Brad Jones, Kathryn Dupnik","doi":"10.20411/pai.v9i2.722","DOIUrl":"10.20411/pai.v9i2.722","url":null,"abstract":"<p><strong>Background: </strong>A primary barrier to curing HIV is the HIV reservoir. The leading infectious cause of death worldwide for people living with HIV is tuberculosis (TB), but we do not know how TB impacts the HIV reservoir.</p><p><strong>Methods: </strong>Participants in identification and validation cohorts were selected from previously enrolled studies at Groupe Haïtien d'Étude du Sarcome de Kaposi et des Infections Opportunistes (GHESKIO) in Port au Prince, Haiti. Intact and non-intact proviral DNA were quantified using droplet digital PCR of peripheral blood mononuclear cell (PBMC)-derived CD4+ T cells. Kruskal-Wallis tests were used to compare medians with tobit regression for censoring.</p><p><strong>Results: </strong>In the identification cohort, we found that people living with HIV with a history of active pulmonary TB (n=19) had higher levels of intact provirus than people living with HIV without a history of active TB (n=47) (median 762; IQR, 183-1173 vs 117; IQR, 24-279 intact provirus per million CD4, respectively; <i>P</i>=0.0001). This difference also was seen in the validation cohort (n=31), (median 102; IQR, 0-737 vs 0; IQR, 0-24.5 intact provirus per million CD4, <i>P</i>=0.03) for TB vs no-TB history groups, respectively. The frequencies of CD4+ T cells with any detectable proviral fragment was directly proportional to the levels of interleukin-1 beta (r=0.524, <i>P</i>= 0.0025) and interleukin-2 (r=0.622, <i>P</i>=0.0002).</p><p><strong>Conclusions: </strong>People living with HIV with a history of active pulmonary TB have more HIV pro-virus in their circulating CD4+ T cells, even years after TB cure. We need to characterize which CD4+ T cells are harboring intact provirus to consider the impact of T cell-targeting HIV cure interventions for people living in TB-endemic areas.</p>","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"9 2","pages":"172-193"},"PeriodicalIF":0.0,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11432494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142355749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dr. Anthony Fauci Shares Insights on His Career and Leadership of the NIAID.","authors":"Michael M Lederman, Neil S Greenspan","doi":"10.20411/pai.v9i2.754","DOIUrl":"10.20411/pai.v9i2.754","url":null,"abstract":"","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"9 2","pages":"152-171"},"PeriodicalIF":0.0,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11418601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sensitivity Analysis of <i>C. auris, S. cerevisiae</i>, and <i>C. cladosporioides</i> by Irradiation with Far-UVC, UVC, and UVB.","authors":"Anna-Maria Gierke, Martin Hessling","doi":"10.20411/pai.v9i2.723","DOIUrl":"10.20411/pai.v9i2.723","url":null,"abstract":"<p><strong>Background: </strong>The World Health Organization has published a list of pathogenic fungi with prior-itizing groups and calls for research and development of antifungal measures, with <i>Candida auris</i> belonging to the group with high priority.</p><p><strong>Methods: </strong>The photosensitivity towards short wavelength ultraviolet irradiation (Far-UVC, UVC, and UVB) was investigated and compared to other yeasts (<i>Saccharomyces cerevisiae</i>) and a mold (<i>Cladosporium cladosporioides</i>). The observed 1-log reduction doses were compared to literature values of other representatives of the genus <i>Candida</i>, but also with <i>S. cerevisiae, Aspergillus niger,</i> and <i>A. fumigatus</i>.</p><p><strong>Results: </strong>For the determined 1-log reduction doses, an increase with higher wavelengths was observed. A 1-log reduction dose of 4.3 mJ/cm² was determined for <i>C. auris</i> when irradiated at 222 nm, a dose of 6.1 mJ/cm² at 254 nm and a 1-log reduction dose of 51.3 mJ/cm² was required when irradiated with UVB.</p><p><strong>Conclusions: </strong>It was observed that <i>S. cerevisiae</i> is a possible surrogate for <i>C. auris</i> for irradiation with Far-UVC and UVB due to close 1-log reduction doses. No surrogate suitability was verified for <i>C. cladosporioides</i> in relation to <i>A. niger</i> and <i>A. fumigatus</i> for irradiation with a wavelength of 254 nm and for <i>A. niger</i> at 222 nm.</p>","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"9 2","pages":"135-151"},"PeriodicalIF":0.0,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11378758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142156238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of SARS-CoV-2 Resistance to Antiviral Monoclonal Antibody Therapy on Neutralizing Antibody Response.","authors":"Marc-Kendy Paul, Manish C Choudhary, Amy L Heaps, Rinki Deo, Daniela Moisi, Kelley C Gordon, John W Mellors, Carlee Moser, Paul Klekotka, Alan Landay, Judith S Currier, Joseph J Eron, Kara W Chew, Davey M Smith, Scott F Sieg, Urvi M Parikh, Jonathan Z Li","doi":"10.20411/pai.v9i2.718","DOIUrl":"10.20411/pai.v9i2.718","url":null,"abstract":"<p><strong>Background: </strong>Anti-SARS-CoV-2 monoclonal antibodies (mAbs) have played a key role as an anti-viral against SARS-CoV-2, but there is a potential for resistance to develop. The interplay between host antibody responses and the development of monoclonal antibody (mAb) resistance is a critical area of investigation. In this study, we assessed host neutralizing antibody (nAb) responses against both ancestral virus and those with treatment-emergent E484K bamlanivimab resistance mutations.</p><p><strong>Methods: </strong>Study participants were enrolled in the ACTIV-2/Advancing Clinical Therapeutics Globally (ACTG) A5401 phase 2 randomized, placebo-controlled trial of bamlanivimab 700 mg mAb therapy (NCT04518410). Anterior nasal and nasopharyngeal swabs were collected for SARS-CoV-2 RNA testing and S gene next-generation sequencing to identify the E484K bamlanivimab resistance mutation. Serum nAb titers were assessed by pseudovirus neutralization assays.</p><p><strong>Results: </strong>Higher baseline (pre-treatment) nAb titers against either ancestral or E484K virus was associated with lower baseline viral load. Participants with emerging resistance had low levels of nAb titers against either ancestral or E484K nAb at the time of study entry. Participants with emergent E484K resistance developed significantly higher levels of E484K-specific nAb titers compared to mAb-treated individuals who did not develop resistance. All participants who developed the E484K mAb resistance mutation were eventually able to clear the virus.</p><p><strong>Conclusion: </strong>Emerging drug resistance after SARS-CoV-2-specific mAb therapy led to a heightened host neutralizing antibody response to the mAb-resistant variant that was associated with eventual viral clearance. This demonstrates the interplay between the antiviral treatment-directed viral evolution and subsequent host immune response in viral clearance.</p>","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"9 2","pages":"79-93"},"PeriodicalIF":0.0,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11378757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142156237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison Study of the Bio-Plex and Meso Scale Multiplexed SARS-CoV-2 Serology Assays Reveals Evidence of Diminished Host Antibody Responses to SARS-CoV-2 after Monoclonal Antibody Treatment.","authors":"Urvi M Parikh, Amy L Heaps, Daniela Moisi, Kelley C Gordon, John W Mellors, Manish C Choudhary, Rinki Deo, Carlee Moser, Paul Klekotka, Alan L Landay, Judith S Currier, Joseph J Eron, Kara W Chew, Davey M Smith, Jonathan Z Li, Scott F Sieg","doi":"10.20411/pai.v9i2.715","DOIUrl":"10.20411/pai.v9i2.715","url":null,"abstract":"<p><strong>Background: </strong>Assessing the breadth and duration of antigen-specific binding antibodies provides valuable information for evaluating interventions to treat or prevent SARS-CoV-2 infection. Multiplex immunoassays are a convenient method for rapid measurement of antibody responses but can sometimes provide discordant results, and antibody positive percent agreement for COVID-19 diagnosis can vary depending on assay type, disease severity, and population sampled. Therefore, we compared two assays marked for research applications, MSD and Bio-Plex Pro, to evaluate qualitative interpretation of serostatus and quantitative detection of antibodies of varying isotypes (IgG, IgM, and IgA) against receptor binding domain (RBD) and nucleocapsid (N) antigens.</p><p><strong>Methods: </strong>Specimens from ACTIV-2/A5401, a placebo-controlled clinical trial of the SARSCoV-2 monoclonal antibody (mAb) bamlanivimab to prevent COVID-19 disease progression, were used to evaluate the concordance of the Bio-Rad Bio-Plex Pro Human SARS-CoV-2 Serology Assay and the Meso Scale Discovery (MSD) V-PLEX COVID-19 Panel 1 serology assay in detecting and quantifying IgG, IgA, and IgM binding anti-SARS-CoV-2 antibody responses against the RBD and N antigens. Data were disaggregated by study arm, bamlanivimab dose, days post-enrollment, and presence of emerging resistance.</p><p><strong>Results: </strong>We observed 90.5% (412 of 455 tests) concordance for anti-RBD IgG and 87% (396 of 455) concordance for anti-N IgG in classifying samples as negative or positive based on assay-defined cutoffs. Antibody levels converted to the WHO standard BAU/mL were significantly correlated for all isotypes (IgG, IgM, and IgA) and SARS-CoV-2 antigen targets (RBD and N) tested that were common between the two assays (Spearman r 0.65 to 0.92, <i>P</i> < 0.0001). Both assays uncovered evidence of diminished host-derived IgG immune responses in participants treated with bamlanivimab compared to placebo. Assessment of immune responses in the four individuals treated with the 700 mg of bamlanivimab with emerging mAb resistance demonstrated a stronger anti-N IgG response (MSD) at day 28 (median 2.18 log BAU/mL) compared to participants treated with bamlanivimab who did not develop resistance (median 1.55 log BAU/mL).</p><p><strong>Conclusions: </strong>These data demonstrate the utility in using multiplex immunoassays for characterizing the immune responses with and without treatment in a study population and provide evidence that monoclonal antibody treatment in acute COVID-19 may have a modest negative impact on development of host IgG responses.</p>","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"9 2","pages":"58-78"},"PeriodicalIF":0.0,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11335343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142009605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic Utility of Pre-Genomic Hepatitis B RNA in the Evaluation of HBV/HIV Coinfection.","authors":"Kenneth E Sherman, Susan D Rouster, Heidi Meeds, Marion G Peters, Jason T Blackard, Paul S Horn, Timothy Archampong, Awewura Kwara, Mark Anderson, Michael Stec, Gavin A Cloherty","doi":"10.20411/pai.v9i2.720","DOIUrl":"10.20411/pai.v9i2.720","url":null,"abstract":"<p><strong>Background: </strong>Newer biomarkers of Hepatitis B virus (HBV) infection and treatment response have not been well-characterized in individuals with HBV/HIV coinfection.</p><p><strong>Methods: </strong>Pre-genomic RNA (pgRNA) and quantitative HBsAg (qHBsAg) were used to evaluate the associations with baseline characteristics. Participants included two separate groups - 236 with HBV/HIV coinfection enrolled in a cross-sectional cohort in Ghana and 47 from an HBV nucleoside/nucleotide treatment trial comparing tenofovir to adefovir in the United States.</p><p><strong>Results: </strong>In both cohorts, HBe antigenemia was highly associated with pgRNA and HBV DNA levels. In the treatment cohort, pre-treatment pgRNA serum concentration was 7.0 log₁₀ U/mL, and mean qHBsAg was 201,297 IU/mL. The observed treatment-associated decrease in pgRNA was consistent with a biphasic decline curve that reached second-phase kinetics following treatment week 12. Changes from baseline were significantly correlated with changes in serum ALT (r = - 0.518; <i>P</i> = 0.023) but not with changes in HBV DNA (r = 0.132, <i>P</i> = NS). qHBsAg also correlated with ALT change (r = - 0.488, <i>P</i> = 0.034).</p><p><strong>Conclusion: </strong>pgRNA and qHBsAg represent newer biomarkers of HBV replication that may help monitor response and treatment outcomes. HBV pgRNA is highly associated with both HBeAg and ALT and may predict both active replication from the closed circular DNA (cccDNA) template as well as hepatic injury.</p>","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"9 2","pages":"43-57"},"PeriodicalIF":0.0,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11318280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Transcriptomic Biomarker Predicting Linezolid-Associated Neuropathy During Treatment of Drug-Resistant Tuberculosis.","authors":"Nika Zielinski, Dragos Baiceanu, Antonela Dragomir, Jan Heyckendorf, Elmira Ibraim, Niklas Köhler, Christoph Leschczyk, Cristina Popa, Andrea Rachow, Jens Sachsenweger, Patricia Sanchez Carballo, Dagmar Schaub, Hajo Zeeb, Begna Tulu, Andrew R DiNardo, Christoph Lange, Maja Reimann","doi":"10.20411/pai.v9i2.705","DOIUrl":"10.20411/pai.v9i2.705","url":null,"abstract":"<p><strong>Background: </strong>Neuropathic adverse events occur frequently in linezolid-containing regimens, some of which remain irreversible after drug discontinuation.</p><p><strong>Objective: </strong>We aimed to identify and validate a host RNA-based biomarker that can predict linezolid-associated neuropathy before multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) treatment initiation and to identify genes and pathways that are associated with linezolid-associated neuropathy.</p><p><strong>Methods: </strong>Adult patients initiating MDR/RR-TB treatment including linezolid were prospectively enrolled in 3 independent cohorts in Germany. Clinical data and whole blood RNA for transcriptomic analysis were collected. The primary outcome was linezolid-associated optic and/or peripheral neuropathy. A random forest algorithm was used for biomarker identification. The biomarker was validated in an additional fourth cohort of patients with MDR/RR-TB from Romania.</p><p><strong>Results: </strong>A total of 52 patients from the 3 identification cohorts received linezolid treatment. Of those, 24 (46.2%) developed peripheral and/or optic neuropathies during linezolid treatment. The majority (59.3%) of the episodes were of moderate (grade 2) severity. In total, the expression of 1,479 genes differed significantly at baseline of treatment. Suprabasin (<i>SBSN</i>) was identified as a potential biomarker to predict linezolid-associated neuropathy. In the validation cohort, 10 of 42 (23.8%) patients developed grade ≥3 neuropathies. The area under the curve for the biomarker algorithm prediction of grade ≥3 neuropathies was 0.63 (poor; 95% confidence interval: 0.42 - 0.84).</p><p><strong>Conclusions: </strong>We identified and preliminarily validated a potential clinical biomarker to predict linezolid-associated neuropathies before the initiation of MDR/RR-TB therapy. Larger studies of the <i>SBSN</i> biomarker in more diverse populations are warranted.</p>","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"9 2","pages":"25-42"},"PeriodicalIF":0.0,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11210591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characteristics and Functions of Infection-enhancing Antibodies to the N-terminal Domain of SARS-CoV-2.","authors":"Ruth I Connor, Mrunal Sakharkar, C Garrett Rappazzo, Chengzi I Kaku, Nicholas C Curtis, Seungmin Shin, Wendy F Wieland-Alter, Jordan Wentworth, Daniel W Mielcarz, Joshua A Weiner, Margaret E Ackerman, Laura M Walker, Jiwon Lee, Peter F Wright","doi":"10.20411/pai.v9i2.679","DOIUrl":"10.20411/pai.v9i2.679","url":null,"abstract":"<p><strong>Background: </strong>Fcγ-receptor (FcγR)-independent enhancement of SARS-CoV-2 infection mediated by N-terminal domain (NTD)-binding monoclonal antibodies (mAbs) has been observed <i>in vitro</i>, but the functional significance of these antibodies <i>in vivo</i> is less clear.</p><p><strong>Methods: </strong>We characterized 1,213 SARS-CoV-2 spike (S)-binding mAbs derived from COVID-19 convalescent patients for binding specificity to the SARS-CoV-2 S protein, VH germ-line usage, and affinity maturation. Infection enhancement in a vesicular stomatitis virus (VSV)-SARS-CoV-2 S pseudovirus (PV) assay was characterized in respiratory and intestinal epithelial cell lines, and against SARS-CoV-2 variants of concern (VOC). Proteomic deconvolution of the serum antibody repertoire was used to determine functional attributes of secreted NTD-binding mAbs.</p><p><strong>Results: </strong>We identified 72/1213 (5.9%) mAbs that enhanced SARS-CoV-2 infection in a PV assay. The majority (68%) of these mAbs recognized the NTD, were identified in patients with mild and severe disease, and persisted for at least 5 months post-infection. Infection enhancement by NTD-binding mAbs was not observed in intestinal and respiratory epithelial cell lines and was diminished or lost against SARS-CoV-2 VOC. Proteomic deconvolution of the serum antibody repertoire from 2 of the convalescent patients identified, for the first time, NTD-binding, infection-enhancing mAbs among the circulating immunoglobulins directly isolated from serum. Functional analysis of these mAbs demonstrated robust activation of FcγRIIIa associated with antibody binding to recombinant S proteins.</p><p><strong>Conclusions: </strong>Functionally active NTD-specific mAbs arise frequently during natural infection and can last as major serum clonotypes during convalescence. These antibodies display functional attributes that include FcγR activation, and may be selected against by mutations in NTD associated with SARS-CoV-2 VOC.</p>","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"9 2","pages":"1-24"},"PeriodicalIF":0.0,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11197847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141459756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Gut and the Translocated Microbiomes in HIV Infection: Current Concepts and Future Avenues","authors":"Krystelle Nganou-Makamdop, Daniel C. Douek","doi":"10.20411/pai.v9i1.693","DOIUrl":"https://doi.org/10.20411/pai.v9i1.693","url":null,"abstract":"It is widely acknowledged that HIV infection results in disruption of the gut’s mucosal integrity partly due a profound loss of gastrointestinal CD4+ T cells that are targets of the virus. In addition, systemic inflammation and immune activation that drive disease pathogenesis are reduced but not normalized by antiretroviral therapy (ART). It has long been postulated that through the process of microbial translocation, the gut microbiome acts as a key driver of systemic inflammation and immune recovery in HIV infection. As such, many studies have aimed at characterizing the gut microbiota in order to unravel its influence in people with HIV and have reported an association between various bacterial taxa and inflammation. This review assesses both contradictory and consistent findings among several studies in order to clarify the overall mechanisms by which the gut microbiota in adults may influence immune recovery in HIV infection. Independently of the gut microbiome, observations made from analysis of microbial products in the blood provide direct insight into how the translocated microbiome may drive immune recovery. To help better understand strengths and limitations of the findings reported, this review also highlights the numerous factors that can influence microbiome studies, be they experimental methodologies, and host-intrinsic or host-extrinsic factors. Altogether, a fuller understanding of the interplay between the gut microbiome and immunity in HIV infection may contribute to preventive and therapeutic approaches.","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"90 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141100960","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}