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Therapeutics and Prevention

  • Open Access
    <span class="named-content genus-species" id="named-content-1">Burkholderia ubonensis</span> Meropenem Resistance: Insights into Distinct Properties of Class A β-Lactamases in <span class="named-content genus-species" id="named-content-2">Burkholderia cepacia</span> Complex and <span class="named-content genus-species" id="named-content-3">Burkholderia pseudomallei</span> Complex Bacteria
    Research Article | Therapeutics and Prevention
    Burkholderia ubonensis Meropenem Resistance: Insights into Distinct Properties of Class A β-Lactamases in Burkholderia cepacia Complex and Burkholderia pseudomallei Complex Bacteria

    Burkholderia pseudomallei causes melioidosis, a tropical disease that is highly fatal if not properly treated. Our data show that, in contrast to B. pseudomallei, B. ubonensis β-lactam resistance is fundamentally different because...

    Nawarat Somprasong, Carina M. Hall, Jessica R. Webb, Jason W. Sahl, David M. Wagner, Paul Keim, Bart J. Currie, Herbert P. Schweizer
  • Open Access
    A Chimeric Japanese Encephalitis Vaccine Protects against Lethal Yellow Fever Virus Infection without Inducing Neutralizing Antibodies
    Research Article | Therapeutics and Prevention
    A Chimeric Japanese Encephalitis Vaccine Protects against Lethal Yellow Fever Virus Infection without Inducing Neutralizing Antibodies

    Efficient and safe vaccines against yellow fever (e.g., YFV-17D) that provide long-lasting protection by rapidly inducing neutralizing antibody responses exist. However, the vaccine supply cannot cope with an increasing demand posed by urban outbreaks in recent years. Here we report that JE-CVax/Imojev, a YFV-17D-based chimeric Japanese encephalitis vaccine, also efficiently protects against YFV infection in mice. In case of shortage of...

    Niraj Mishra, Robbert Boudewijns, Michael Alexander Schmid, Rafael Elias Marques, Sapna Sharma, Johan Neyts, Kai Dallmeier
  • Open Access
    Single-Dose, Intranasal Immunization with Recombinant Parainfluenza Virus 5 Expressing Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Spike Protein Protects Mice from Fatal MERS-CoV Infection
    Research Article | Therapeutics and Prevention
    Single-Dose, Intranasal Immunization with Recombinant Parainfluenza Virus 5 Expressing Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Spike Protein Protects Mice from Fatal MERS-CoV Infection

    MERS-CoV causes lethal infection in humans, and there is no vaccine. Our work demonstrates that PIV5 is a promising vector for developing a MERS vaccine. Furthermore, success of PIV5-based MERS vaccine can be employed to develop a vaccine for emerging CoVs such as SARS-CoV-2, which causes COVID-19.

    Kun Li, Zhuo Li, Christine Wohlford-Lenane, David K. Meyerholz, Rudragouda Channappanavar, Dong An, Stanley Perlman, Paul B. McCray, Biao He
  • Open Access
    A Lassa Virus Live-Attenuated Vaccine Candidate Based on Rearrangement of the Intergenic Region
    Research Article | Therapeutics and Prevention
    A Lassa Virus Live-Attenuated Vaccine Candidate Based on Rearrangement of the Intergenic Region

    Lassa virus (LASV), the causative agent of Lassa fever, infects several hundred thousand people in Western Africa, resulting in many lethal Lassa fever cases. No U.S. Food and Drug Administration-licensed countermeasures are available to prevent or treat LASV infection. We describe the generation of a novel LASV live-attenuated vaccine candidate rLASV(IGR/S-S), which is based on the replacement of the large genomic segment noncoding...

    Yingyun Cai, Masaharu Iwasaki, Daisuke Motooka, David X. Liu, Shuiqing Yu, Kurt Cooper, Randy Hart, Ricky Adams, Tracey Burdette, Elena N. Postnikova, Jonathan Kurtz, Marisa St. Claire, Chengjin Ye, Jens H. Kuhn, Luis Martínez-Sobrido, Juan Carlos de la Torre
  • Open Access
    Neutralizing Monoclonal Antibodies against the Gn and the Gc of the Andes Virus Glycoprotein Spike Complex Protect from Virus Challenge in a Preclinical Hamster Model
    Research Article | Therapeutics and Prevention
    Neutralizing Monoclonal Antibodies against the Gn and the Gc of the Andes Virus Glycoprotein Spike Complex Protect from Virus Challenge in a Preclinical Hamster Model

    Infections with New World hantaviruses are associated with high case fatality rates, and no specific vaccine or treatment options exist. Furthermore, the biology of the hantaviral GnGc complex, its antigenicity, and its fusion machinery are poorly understood. Protective monoclonal antibodies against GnGc have the potential to be developed into therapeutics against hantaviral disease and are also great tools to elucidate the biology of...

    James Duehr, Meagan McMahon, Brandi Williamson, Fatima Amanat, Alan Durbin, David W. Hawman, Danny Noack, Skyler Uhl, Gene S. Tan, Heinz Feldmann, Florian Krammer
  • Open Access
    Hiding in Plain Sight: an Approach to Treating Patients with Severe COVID-19 Infection
    Commentary | Therapeutics and Prevention
    Hiding in Plain Sight: an Approach to Treating Patients with Severe COVID-19 Infection

    Patients with COVID-19 infection are at risk of acute respiratory disease syndrome (ARDS) and death. The tissue receptor for COVID-19 is ACE2, and higher levels of ACE2 can protect against ARDS. Angiotensin receptor blockers and statins upregulate ACE2. Clinical trials are needed to determine whether this drug combination might be used to treat patients with severe COVID-19 infection.

    David S. Fedson, Steven M. Opal, Ole Martin Rordam
  • Open Access
    Sulfamoyl Heteroarylcarboxylic Acids as Promising Metallo-β-Lactamase Inhibitors for Controlling Bacterial Carbapenem Resistance
    Research Article | Therapeutics and Prevention
    Sulfamoyl Heteroarylcarboxylic Acids as Promising Metallo-β-Lactamase Inhibitors for Controlling Bacterial Carbapenem Resistance

    Carbapenem antibiotics are the last resort for control of severe infectious diseases, bloodstream infections, and pneumonia caused by Gram-negative bacteria, including Enterobacteriaceae. However, carbapenem-resistant Enterobacteriaceae (CRE) strains have spread globally and are a critical concern in clinical settings because CRE infections are recognized as a leading cause of increased mortality among hospitalized...

    Jun-ichi Wachino, Wanchun Jin, Kouji Kimura, Hiromasa Kurosaki, Ayato Sato, Yoshichika Arakawa
  • Open Access
    A Solution to Antifolate Resistance in Group B <em>Streptococcus</em>: Untargeted Metabolomics Identifies Human Milk Oligosaccharide-Induced Perturbations That Result in Potentiation of Trimethoprim
    Research Article | Therapeutics and Prevention
    A Solution to Antifolate Resistance in Group B Streptococcus: Untargeted Metabolomics Identifies Human Milk Oligosaccharide-Induced Perturbations That Result in Potentiation of Trimethoprim

    Group B Streptococcus is an important human pathogen that causes serious infections during pregnancy which can lead to chorioamnionitis, funisitis, premature rupture of gestational membranes, preterm birth, neonatal sepsis, and death. GBS is evolving antimicrobial resistance mechanisms, and the work presented in this paper provides evidence that prebiotics such as human milk oligosaccharides can act as adjuvants to restore the...

    Schuyler A. Chambers, Rebecca E. Moore, Kelly M. Craft, Harrison C. Thomas, Rishub Das, Shannon D. Manning, Simona G. Codreanu, Stacy D. Sherrod, David M. Aronoff, John A. McLean, Jennifer A. Gaddy, Steven D. Townsend
  • Open Access
    Translation Inhibition by Rocaglates Activates a Species-Specific Cell Death Program in the Emerging Fungal Pathogen <span class="named-content genus-species" id="named-content-1">Candida auris</span>
    Research Article | Therapeutics and Prevention
    Translation Inhibition by Rocaglates Activates a Species-Specific Cell Death Program in the Emerging Fungal Pathogen Candida auris

    Emergence of the fungal pathogen Candida auris has ignited intrigue and alarm within the medical community and the public at large. This pathogen is unusually resistant to antifungals, threatening to overwhelm current management options. By screening a library of structurally diverse molecules, we found that...

    Kali R. Iyer, Luke Whitesell, John A. Porco, Thomas Henkel, Lauren E. Brown, Nicole Robbins, Leah E. Cowen
  • Open Access
    Vaccine-Induced Th1-Type Response Protects against Invasive Group A <em>Streptococcus</em> Infection in the Absence of Opsonizing Antibodies
    Research Article | Therapeutics and Prevention
    Vaccine-Induced Th1-Type Response Protects against Invasive Group A Streptococcus Infection in the Absence of Opsonizing Antibodies

    Availability of a group A Streptococcus vaccine remains an unmet public health need. Here, we tested different adjuvant formulations to improve the protective efficacy of non-M protein vaccine Combo5 in an invasive disease model. We show that novel adjuvants can dramatically shape the type of immune response developed following immunization with Combo5 and significantly improve protection. In addition, protection afforded by...

    Tania Rivera-Hernandez, Mira Syahira Rhyme, Amanda J. Cork, Scott Jones, Celia Segui-Perez, Livia Brunner, Johanna Richter, Nikolai Petrovsky, Maria Lawrenz, David Goldblatt, Nicolas Collin, Mark J. Walker

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