ACS Infectious Diseases最新文献

{"title":"Synthesis of Innovative Photosensitizers for Enhanced Photodynamic Therapy of Drug-Resistant Pathogens and Biofilms.","authors":"Hongshuang Qin, Yanxiang Guo, Chenjie Ma, Caihong Zhang, Ke Gao, Xueyi Sun, Chuanqi Zhao, Tao Liu","doi":"10.1021/acsinfecdis.5c00564","DOIUrl":"https://doi.org/10.1021/acsinfecdis.5c00564","url":null,"abstract":"<p><p>Antimicrobial photodynamic therapy (aPDT) has emerged as a potential approach to combating infections triggered by drug-resistant bacteria. However, the selection of photosensitizers for aPDT remains restricted, highlighting the urgent need to develop novel and efficient photosensitizers. Questiomycin A (QA) has garnered attention due to its diverse biomedical activities and good biocompatibility. However, the photodynamic effects of QA and its derivatives have not been explored. Investigating the photodynamic activities of QA-based compounds can provide innovative molecular structures for photosensitizer development. Herein, five derivatives (C1, C2, C3, C4, and C5) of QA are synthesized, and the aPDT activities of these compounds against methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) are assessed. Our findings show that C5- and QA-mediated aPDT exhibits notable bactericidal efficacy, which is better than that of the well-known photosensitizer methylene blue. Especially C5 overcomes the drawbacks associated with the excitation of QA by blue-violet light, such as DNA damage and poor tissue penetration. Mechanism analyses reveal that C5-aPDT can induce singlet oxygen (¹O₂) generation to disrupt bacterial structures and functions, as well as eradicate biofilms and MRSA within biofilms. Studies in the mouse infection model indicate that C5-aPDT markedly promotes wound healing and exhibits excellent biocompatibility with a hemolysis rate of only 0.59% and minimal cell viability inhibition (2.96%) at therapeutic concentrations. To our knowledge, this is the first report that QA derivatives possess outstanding photodynamic activities, providing a unique molecular structure for the design of photosensitizers.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145317946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Duplex Enzymatic Recombinase Amplification Assay Coupled with Lateral Flow Dipstick for Rapid Identification of Methicillin-Resistant <i>Staphylococcus aureus</i>.","authors":"Arpasiri Srisrattakarn, Aroonwadee Chanawong, Orapan Sripichai, Jenjira Rujidamp, Neeranuch Maneenet, Nannapat Onsapiw, Thiwawan Bunleuhan, Aroonlug Lulitanond","doi":"10.1021/acsinfecdis.5c00576","DOIUrl":"https://doi.org/10.1021/acsinfecdis.5c00576","url":null,"abstract":"<p><p>46 clinical isolates, 28 <i>nuc</i>-carrying and 18 <i>nuc</i>-negative isolates, and 23 <i>mecA</i>-carrying and 23 <i>mecA</i>-negative isolates were subjected to a developed duplex isothermal enzymatic recombinase amplification assay accompanied by a lateral flow assay (ERA-LFA) method for methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) detection. Additionally, 57 positive blood culture samples from patients were evaluated for preliminary testing. The sensitivity and specificity among the 46 clinical samples were 100% (28/28) and 88.9% (16/18), respectively, for <i>nuc</i> detection, and 100.0% (23/23 and 23/23) for <i>mecA</i> detection. For the 57 positive blood culture bottles, the ERA-LFA provided 100.0% (34/34) sensitivity and 95.7% (22/23) specificity for <i>nuc</i> detection and 96.5% specificity (55/57) for <i>mecA</i> detection. The detection limits of the ERA-LFA for the <i>nuc</i> and <i>mecA</i> genes were 1 and 10 CFU/reaction, respectively.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145306403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of β-Carboline Derivatives Reveals a High Barrier to Resistance and Potent Activity against Ring-Stage and DHA-Induced Dormant <i>Plasmodium falciparum</i>.","authors":"Reagan S Haney, Joshua H Butler, Lyric A Wardlaw, Emilio F Merino, Victoria Mendiola, Caitlin A Cooper, Jopaul Mathew, Patrick K Tumwebaze, Philip J Rosenthal, Roland A Cooper, Dennis E Kyle, Zaira Rizopoulos, Delphine Baud, Stephen Brand, Maxim Totrov, Paul R Carlier, Maria Belen Cassera","doi":"10.1021/acsinfecdis.5c00714","DOIUrl":"https://doi.org/10.1021/acsinfecdis.5c00714","url":null,"abstract":"<p><p>Malaria, caused by <i>Plasmodium falciparum</i>, remains a major global health challenge, with an estimated 263 million new infections and 597,000 deaths annually. Increasing resistance to current antimalarial drugs underscores the urgent need for new therapeutics that target novel pathways in the parasite. We previously reported a novel class of β-carboline antimalarials, exemplified by PRC1584, which demonstrated a favorable oral pharmacokinetic profile, <i>in vivo</i> efficacy in <i>Plasmodium berghei</i>-infected mice, and no cross-resistance with other antimalarials in various <i>P. falciparum</i> strains. In this study, we demonstrate that PRC1584 exhibits a high resistance barrier and retains potent activity against fresh Ugandan <i>P. falciparum</i> isolates. PRC1584, along with its more potent analog PRC1697, demonstrated strong <i>in vitro</i> potency against both actively proliferating ring stages and dihydroartemisinin-induced dormant stages. Additionally, our study demonstrated that PfKelch13-C580Y mutation was associated with an increased susceptibility to PRC1584, whereas PfKelch13-R549T and Pfcoronin-R100 K-E107V mutations were not associated with this effect. These findings underscore the therapeutic potential of this new \"irresistible\" compound class, support a possible novel mechanism of action, and suggest the future development of novel ACTs active against resistant parasites by targeting DHA dormancy, an essential survival mechanism of <i>P. falciparum</i>.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145306405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery and Evaluation of a Methylpyrazolopyrimidine Antibacterial Active against Methicillin-Resistant <i>Staphylococcus aureus</i>.","authors":"Caitlyn A Thomas, Choon Kim, Amr M El-Araby, Biruk Tesfaye Birhanu, Van T Nguyen, Valerie A Schroeder, Jed F Fisher, Mayland Chang, Shahriar Mobashery","doi":"10.1021/acsinfecdis.5c00685","DOIUrl":"https://doi.org/10.1021/acsinfecdis.5c00685","url":null,"abstract":"<p><p>Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) is a nefarious human bacterial pathogen classified as a serious threat. MRSA strains are resistant to virtually all β-lactam antibiotics (including penicillins and cephalosporins). A common resistance mechanism to β-lactams is mediated by the function of the <i>bla</i> operon, which encodes a β-lactam sensor/signal transducer protein BlaR, a gene repressor BlaI, and a resistance determinant: a class A β-lactamase (BlaZ) and/or a unique penicillin-binding protein 2a (PBP2a). BlaR is responsible for sensing the presence of β-lactam antibiotics and transducing a signal to its cytoplasmic domain upon binding covalently to the β-lactam. This triggers a series of cytoplasmic events that culminate in full-blown antibiotic resistance. We have used a fluorescence-reporter assay in live <i>S. aureus</i> to screen two NCI compound libraries─natural product and diversity libraries─comprising 1,974 compounds for both antibacterial and antibiotic-potentiation activities. Compound <b>1</b>, <i>N</i>⁴,<i>N</i>⁶<i>-bis</i>(4-bromophenyl)-1-methyl-1<i>H</i>-pyrazolo[3,4-<i>d</i>]pyrimidine-4,6-diamine, emerged from these assays as a potentiator of the activity of oxacillin (a second-generation penicillin), while also exhibiting antibacterial activity of its own. The compound binds to the BlaR sensor domain (31 μM) in shutting down the <i>bla</i> operon, and also binds to the structurally related PBP2 and PBP2a, which are both critical targets for cell wall assembly. Scanning electron microscopy documented cell wall damage caused by compound <b>1</b> in combination with oxacillin.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145306428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Strain-Level Typing of <i>Streptococcus pyogenes</i> Using Optical DNA Mapping.","authors":"Radhika N Kunnath, Zahra Abbaspour, Anna Johnning, Karolin Frykholm, Marie Wrande, Albertas Dvirnas, Sriram Kk, Christian G Giske, Tobias Ambjörnsson, Linus Sandegren, Erik Kristiansson, Fredrik Westerlund","doi":"10.1021/acsinfecdis.5c00430","DOIUrl":"https://doi.org/10.1021/acsinfecdis.5c00430","url":null,"abstract":"<p><p><i>Streptococcus pyogenes</i>, also known as group A <i>Streptococcus</i> (GAS), is a Gram-positive bacterial pathogen responsible for approximately 500,000 deaths globally per year. Therefore, surveillance of invasive GAS infections is of critical importance in understanding societal transmission. In this study, we propose an optical DNA mapping (ODM)-based assay for strain-level typing of <i>S. pyogenes</i>. Fluorescently labeled DNA molecules of lengths >150 kbp are stretched in nanochannels and imaged to reveal genomic information. A core genome alignment-based typing scheme is then utilized for identification at the strain level. Although our technique lacks the nucleotide-level resolution of whole-genome sequencing, it excels at detecting patterns across long stretches of DNA that remain inaccessible to short-read sequencing methods. Using clinical isolates, we demonstrate that the ODM assay can identify <i>S. pyogenes</i> at both the species level and at even higher taxonomic resolutions with high accuracy. Our typing scheme also shows a high correlation with standard <i>emm</i> subtyping for the analyzed samples. We conclude that ODM has the potential to deliver timely and cost-efficient strain-level bacterial identification.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145290391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anthelmintics Derived from the Kinase Inhibitor SGI-1776 for the Treatment of Gastrointestinal Worm Infections.","authors":"Mostafa A Elfawal, Victoria Banas, Bruce A Rosa, Matthew Mahoney, Emily Goetz, Paulina Chen, Raffi V Aroian, James W Janetka, Makedonka Mitreva","doi":"10.1021/acsinfecdis.5c00585","DOIUrl":"https://doi.org/10.1021/acsinfecdis.5c00585","url":null,"abstract":"<p><p>Human gastrointestinal nematodes (GINs) infect at least one billion people, mostly children, with five billion people at risk of infection. Reduced and low efficacy of currently used anthelmintics, e.g., benzimidazoles against <i>Trichuris trichiura</i> whipworms, urges new anthelmintics to control these parasites. We previously discovered two human <i>pan</i>-PIM kinase inhibitors, CX-6258 and SGI-1776, with potent antihelmintic activity against GINs. Here, structure-activity relationship (SAR) studies were conducted to identify SGI-1776 analogs with improved cross-clade adulticidal activity (<i>Ancylostoma ceylanicum</i> hookworms and <i>Trichuris muris</i> whipworms). We further identified a new chemical series from <b>15</b> (imidazo[1,2-<i>b</i>]pyridazine-3-carboxamide) and novel derivatives from it. Differential cuticle permeability, quantified by the amount of bioaccumulated drugs, explained some unexpected observations regarding activity and correlated with their physicochemical properties. The compounds' physical properties were significantly predictive of their activity. <b>15</b> and <b>51</b> were the most potent against whipworm and showed decreased and no activity against human PIM kinases, suggesting increased selectivity against the GIN counterparts. The unexpected SAR of compound <b>15</b> can be explained by computational modeling. We demonstrate the efficacy of optimized compound <b>50</b> as a new oral anthelmintic, which demonstrated better gut restriction properties and significantly reduced the fecundity of <i>T. muris</i> whipworm adults in infected mice. We also report our findings on physicochemical properties and gut restriction ADME parameters that are essential for further lead optimization.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutrophils from Protection to Pathogenesis in Tuberculosis.","authors":"Hussain Beig, Amit Singh","doi":"10.1021/acsinfecdis.5c00096","DOIUrl":"https://doi.org/10.1021/acsinfecdis.5c00096","url":null,"abstract":"<p><p><i>Mycobacterium tuberculosis</i> (<i>Mtb</i>), the etiological agent of tuberculosis (TB), is well-equipped to establish infection, endure host immune pressures, and propagate to naïve individuals; its success depends on its ability to actively evade and recalibrate the host immune system. The balance between immunological control and bacterial persistence often shapes the clinical outcome of an <i>Mtb</i> infection. While the roles of macrophages and T cells have been extensively characterized in this balance, the contribution of neutrophils remains comparatively underexplored. The abundance of neutrophils in TB granulomas and their correlation with disease severity in humans and animal models suggest a vital role for these immune cells in TB infection. This review summarizes our current understanding of neutrophils in TB pathogenesis at different scales and models─in vitro, ex vivo, and in vivo─while highlighting some of the outstanding questions at each level. We delve into emerging concepts in neutrophil biology, including heterogeneity, metabolism, and maturation, along with <i>Mtb</i>'s mechanisms to modulate and evade neutrophil bactericidal stresses to ensure its persistence. A deeper understanding of neutrophil biology and the interaction with <i>Mtb</i> could inform the development of more effective therapies and diagnostic strategies against TB.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145290367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Examination of Acetylated Monosaccharides as Metabolic Probes in Bacteria.","authors":"Sophia E Nigrovic, Ankita Paul, Soumyakanta Maji, Antara Ghosh, Jack Tran, Phuong Luong, William J Rackear, Elizabeth A Stemmler, Karen D Moulton, Suvarn S Kulkarni, Danielle H Dube","doi":"10.1021/acsinfecdis.5c00765","DOIUrl":"https://doi.org/10.1021/acsinfecdis.5c00765","url":null,"abstract":"<p><p>Bacterial glycans are validated antibiotic targets due to their crucial roles in supporting bacterial fitness and survival. The array of exclusively bacterial monosaccharides and their variable expression across bacterial species and serotypes present challenges in studying these structurally diverse molecules. Probes based on bacterial sugars have emerged as useful tools in metabolic labeling studies. Prior to the metabolic processing of probes by bacteria, most metabolic probes must be transported across the bacterial cell envelope. Probe acetylation has been used as one strategy to ease passive diffusion across the lipophilic cell membrane and relies on deacetylation by esterases within cells before subsequent metabolic processing into glycans is possible. However, inefficient probe deacetylation has the potential to yield artifactual labeling rather than physiological glycan labeling. Here, we systematically explored probe acetylation as a design criterion for metabolic labeling experiments in four bacterial species. <i>Plesiomonas shigelloides</i>, <i>Vibrio vulnificus</i>, and <i>Helicobacter pylori</i> exhibited a strong preference for metabolic incorporation of acetylated probes relative to unprotected probes, whereas <i>Bacteroides fragilis</i> incorporated both unprotected and acetylated probes at comparable levels. Curiously, only <i>B. fragilis</i> had sufficient esterase activity to quantitatively deacetylate a peracetylated monosaccharide probe in situ. These findings suggest the importance of validating acetylated probes on a case-by-case basis to ensure physiologically relevant bacterial glycan labeling.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Yet to SET: <i>Plasmodium falciparum</i> Histone Lysine Methyltransferases.","authors":"Disha Shah, Krishanpal Karmodiya","doi":"10.1021/acsinfecdis.5c00578","DOIUrl":"https://doi.org/10.1021/acsinfecdis.5c00578","url":null,"abstract":"<p><p>Malaria caused by <i>Plasmodium falciparum</i> continues to remain a global health challenge. Its prevention, treatment and elimination efforts are threatened by the inevitable emergence of drug resistance to currently effective treatment regimes. New antimalarials with distinct modes of action and multistage and multispecies activity will be an important addition to the arms race against the malarial parasite. <i>P. falciparum</i>'s epigenome represents a promising target in this battle and offers exciting opportunities for targeted intervention. With an unusually AT-rich genome, a relative paucity of specific transcription factors and limited heterochromatin, epigenetic control has emerged as an important contributor to <i>P. falciparum</i>'s survival and virulence. <i>P. falciparum</i> histones are marked dynamically with a vast array of post translational modifications. These include several well studied and some novel marks. The parasite has an epigenetic signature distinct from its host and shows several parasite-specific adaptations. The regulators of these marks remain understudied, however. While histone acetylation and its regulators have been more extensively studied in the field, research on other epigenetic effectors is also catching up. This review highlights the research efforts aimed at understanding the role of the parasite's histone lysine methyltransferases in shaping transcriptional regulation and the histone modification landscape.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hantavirus Gn^H Nanoparticle Immunogen Elicits a Cross-Neutralizing Antibody Response in Mice.","authors":"Kevin E Ramos, Margarette C Mariano, Eva Mittler, Romina Pardo, Vanessa Zylberman, Pablo Guardado-Calvo, Kartik Chandran, Jonathan R Lai","doi":"10.1021/acsinfecdis.5c00415","DOIUrl":"https://doi.org/10.1021/acsinfecdis.5c00415","url":null,"abstract":"<p><p>Hantaviruses are zoonotic pathogens that are spread by rodents and can cause severe and fatal disease in humans. \"New World\" hantaviruses (endemic to North and South America) include the human pathogenic <i>Andes orthohantavirus</i> (ANDV), <i>Choclo orthohantavirus</i> (CHOV), and <i>Sin Nombre orthohantavirus</i> (SNV). Human infections can lead to hantavirus cardiopulmonary syndrome (HCPS), which is associated with ∼40% mortality. Currently, there are no FDA-approved hantavirus vaccines or treatments, but neutralizing antibodies targeting the glycoproteins Gn and Gc have been shown to be protective in animals. Here, we develop nanoparticle immunogens bearing the Gn head domain (Gn^H) from ANDV, CHOV, or SNV. Initial immunization studies with the ANDV-Gn^H monomer indicated that this antigen elicited a reactive but non-neutralizing antibody response in mice. To bolster the immune response, we developed a strategy to link Gn^Hs to mi3 nanoparticles using the SpyCatcher/SpyTag bioconjugation technology. We found that ANDV-Gn^H-mi3 nanoparticles elicited a cross-reactive antibody response that neutralized pseudotyped viruses containing ANDV and CHOV glycoproteins but not SNV. In contrast, CHOV-Gn^H-mi3 nanoparticles elicited only a homotypic neutralizing response. Finally, the reactivity of sera from mice immunized with a cocktail of ANDV-Gn^H-mi3 and SNV-Gn^H-mi3 nanoparticles was similar to sera from mice immunized with ANDV-Gn^H-mi3, only indicating that the SNV-Gn^H-mi3 antibody response was not even homotypically neutralizing. These results suggest that there are differences in immunodominance that may contribute to the breadth of the hantavirus-targeting neutralizing response elicited by Gn^H-based immunogens. Nonetheless, the cross-neutralizing sera obtained by ANDV-Gn^H-mi3 immunization suggest that developing broad immunogens may be possible with appropriate engineering.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145278487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}