Article
Immunology
Joanne Marie M. Del Rosario, Kelly A. S. da Costa, Benedikt Asbach, Francesca Ferrara, Matteo Ferrari, David A. Wells, Gurdip Singh Mann, Veronica O. Ameh, Claude T. Sabeta, Ashley C. Banyard, Rebecca Kinsley, Simon D. Scott, Ralf Wagner, Jonathan L. Heeney, George W. Carnell, Nigel J. Temperton
Summary: A library of influenza hemagglutinin (HA) pseudotypes was developed for use in influenza neutralization assays, demonstrating high sensitivity and specificity for detecting virus-specific neutralizing antibodies and assessing antibody functionality. These HA pseudotypes can serve as substitutes for wildtype viruses in experiments and are valuable for evaluating cross-subtype immune responses elicited by vaccines.
Article
Microbiology
Ekaterina O. Sinegubova, Olga A. Kraevaya, Aleksandrina S. Volobueva, Alexander V. Zhilenkov, Alexander F. Shestakov, Sergey V. Baykov, Pavel A. Troshin, Vladimir V. Zarubaev
Summary: The influenza virus has a high mutation rate, resulting in rapid emergence of drug-resistant strains. Therefore, there is a need for the development of new broad-spectrum antivirals against influenza. This study describes derivatives based on fullerenes that have broad virus inhibiting activities against a panel of influenza viruses. Compound 2, containing residues of salts of 2-amino-3-cyclopropylpropanoic acid, exhibited the highest antiviral activity and lowest toxicity.
Article
Engineering, Biomedical
Steven J. Frey, Juan Manuel Carreno, Dominika Bielak, Ammar Arsiwala, Clara G. Altomare, Chad Varner, Tania Rosen-Cheriyan, Goran Bajic, Florian Krammer, Ravi S. Kane
Summary: Despite licensed vaccines being available, influenza still leads to significant illness and death globally. Current vaccines mainly target the head domain of the viral protein hemagglutinin (HA), but influenza viruses can easily evade this response by acquiring mutations in the head domain. This study demonstrates that nanoparticles presenting HA in an inverted orientation generate higher levels of antibodies and a broader immune response against the conserved stalk domain, providing better protection against the virus. By controlling antigen orientation, it may be possible to design nanovaccines that offer broad protection against influenza and other potential pandemic pathogens.
ADVANCED HEALTHCARE MATERIALS
(2023)
Article
Cell Biology
Yongbo Qiao, Shenghui Jin, Jiaojiao Nie, Yaotian Chang, Bo Wang, Shanshan Guan, Qinghan Li, Yuhua Shi, Wei Kong, Yaming Shan
Summary: The use of recombinant trimeric hemagglutinin (HA) as an antigen in a DNA vaccine shows promise as a competitive candidate vaccine against influenza viruses. It elicits significant immune responses and provides protection against lethal infection.
JOURNAL OF LEUKOCYTE BIOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Carly M. Bliss, Alec W. Freyn, Tom G. Caniels, Victor H. Leyva-Grado, Raffael Nachbagauer, Weina Sun, Gene S. Tan, Virginia L. Gillespie, Meagan McMahon, Florian Krammer, Adrian V. S. Hill, Peter Palese, Lynda Coughlan
Summary: Conventional influenza vaccines fail to provide broad protection against diverse influenza A viruses. However, this study presents a non-replicating adenoviral vaccine that can elicit broad and cross-reactive protection against multiple strains of influenza A in mice.
Article
Microbiology
Ki-Hye Kim, Zhuo Li, Noopur Bhatnagar, Jeeva Subbiah, Bo Ryoung Park, Chong Hyun Shin, Peter Pushko, Bao-Zhong Wang, Sang-Moo Kang
Summary: The study developed a universal influenza vaccine candidate that can provide broad cross protection against diverse influenza A and B viruses, and is effective in both young and aged mice.
Article
Cell Biology
Ching-Lin Hsieh, Anne P. Werner, Sarah R. Leist, Laura J. Stevens, Ester Falconer, Jory A. Goldsmith, Chia-Wei Chou, Olubukola M. Abiona, Ande West, Kathryn Westendorf, Krithika Muthuraman, Ethan J. Fritch, Kenneth H. Dinnon, Alexandra Schafer, Mark R. Denison, James D. Chappell, Ralph S. Baric, Barney S. Graham, Kizzmekia S. Corbett, Jason S. McLellan
Summary: This study developed stabilized stem (SS) antigens by removing the S1 subunit from the Middle East respiratory syndrome (MERS)-CoV spike (S) glycoprotein using structure-guided protein engineering. Vaccination with MERS SS elicited cross-reactive b-CoV antibody responses and protected mice against lethal MERS-CoV challenge. The discovery of a panel of cross-reactive monoclonal antibodies, among which IgG22 showed high affinity binding to both MERS-CoV and severe acute respiratory syndrome (SARS)-CoV-2 S proteins, indicates the potential for cross-reactive CoV antibodies.
Article
Chemistry, Physical
Ming Xia, Md Rejaul Hoq, Pengwei Huang, Wen Jiang, Xi Jiang, Ming Tan
Summary: A new vaccine strategy has been developed to enhance immune responses against influenza viruses by generating PVNPs displaying HA1 antigens, which has shown promising results in experiments.
Article
Immunology
Sneha Raj, Preeti Vishwakarma, Shikha Saxena, Varun Kumar, Ritika Khatri, Amit Kumar, Mrityunjay Singh, Surbhi Mishra, Shailendra Asthana, Shubbir Ahmed, Sweety Samal
Summary: A stable trimeric HA protein was expressed and purified from a highly virulent Inf A/Guangdong-Maonan/ SWL1536/2019 virus. The trimeric HA protein showed complete protection against a high lethal dose of homologous and mouse-adapted InfA/PR8 virus challenge in a mouse model through intradermal immunization. Additionally, the immunogen induced high hemagglutinin inhibition (HI) titers and cross-protection against other Inf A and Inf B subtypes.
Article
Microbiology
Ki-Hye Kim, Zhuo Li, Noopur Bhatnagar, Jeeva Subbiah, Bo Ryoung Park, Chong Hyun Shin, Peter Pushko, Bao-Zhong Wang, Sang-Moo Kang
Summary: This study developed a virus-like particle that can induce immune responses against multiple subtypes of influenza viruses. The vaccination provided broad protection against different strains of influenza A and B viruses. The findings suggest the potential of developing a universal vaccine against influenza in both young and aged populations.
Review
Immunology
Arun B. Arunachalam, Penny Post, Deborah Rudin
Summary: The RIV4 influenza vaccine, produced through recombinant technology, has distinct post-translational modifications and structural features that result in high levels of protective antibodies. Compared to traditional influenza vaccines, RIV4 has advantages in reducing reliance on virus and process impurities, and improving the breadth of immune responses.
Article
Immunology
Eleni Vatzia, Katherine Feest, Adam McNee, Tanuja Manjegowda, B. Veronica Carr, Basudev Paudyal, Tiphany Chrun, Emmanuel A. A. Maze, Amy Mccarron, Susan Morris, Helen E. E. Everett, Ronan MacLoughlin, Francisco J. J. Salguero, Teresa Lambe, Sarah C. C. Gilbert, Elma Tchilian
Summary: The study found that immunization with chimpanzee adenovirus and modified vaccinia Ankara vaccines expressing conserved influenza virus proteins can provide enhanced immune responses against H3N2 influenza and reduce viral shedding and lung pathology. The results are significant for the development of a broadly protective influenza vaccine and will contribute to future vaccine and clinical trial design.
Letter
Immunology
Wenming Jiang, Chunxia Dong, Shuo Liu, Cheng Peng, Xin Yin, Shaobo Liang, Lin Zhang, Jinping Li, Xiaohui Yu, Yang Li, Jingjing Wang, Guangyu Hou, Zheng Zeng, Hualei Liu
Summary: A novel highly pathogenic avian influenza A(H5N6) clade 2.3.4.4b virus was isolated from a poultry market in China that a person with a confirmed case had visited. Most genes of the avian and human H5N6 isolates were closely related. The virus also exhibited distinct antigenicity to the Re-11 vaccine strain.
EMERGING INFECTIOUS DISEASES
(2022)
Article
Biochemical Research Methods
Deborah Chang, Joshua Klein, William E. Hackett, Mary Rachel Nalehua, Xiu-Feng Wan, Joseph Zaia
Summary: Glycosylation plays a critical role in the function and evolution of influenza A virus hemagglutinin (HA). The use of data-independent acquisition mass spectrometry allows for quantitative measurement of glycosylation changes and comparison between different viral expression systems and variants.
MOLECULAR & CELLULAR PROTEOMICS
(2022)
Article
Virology
Kaituo Liu, Yaqian Guo, Huafen Zheng, Zhuxing Ji, Miao Cai, Ruyi Gao, Pinghu Zhang, Xiaowen Liu, Xiulong Xu, Xiaoquan Wang, Xiufan Liu
Summary: H9N2 avian influenza viruses have become dominant in China and this study identified amino acid substitutions in the HA protein that enhance viral replication and virulence in mice. These mutations also enable viral transmission in guinea pigs. The study provides valuable insights into pandemic preparedness against emerging H9N2 strains.
Article
Chemistry, Analytical
Yanjun Yang, Jackelyn Murray, James Haverstick, Ralph A. Tripp, Yiping Zhao
Summary: The researchers developed a rapid coronavirus detection method using a functionalized silver nanotriangle array localized surface plasmon resonance sensor. The sensor shows high sensitivity and specificity in detecting SARS-CoV-2 infection, and the detection time is less than 20 minutes.
SENSORS AND ACTUATORS B-CHEMICAL
(2022)
Article
Multidisciplinary Sciences
Naoki Iwanaga, Laura Cooper, Lijun Rong, Nicholas J. Maness, Brandon Beddingfield, Zhongnan Qin, Jackelyn Crabtree, Ralph A. Tripp, Haoran Yang, Robert Blair, Sonia Jangra, Adolfo Garcia-Sastre, Michael Schotsaert, Sruti Chandra, James E. Robinson, Akhilesh Srivastava, Felix Rabito, Xuebin Qin, Jay K. Kolls
Summary: Researchers constructed an ACE2-human IgG1 fusion protein with mutations in the catalytic domain of ACE2, which significantly increased binding to SARS-CoV-2 spike protein and improved lung infection caused by the virus in vivo. This study suggests that MDR504 hACE2-Fc may be a promising candidate for the treatment or prevention of COVID-19 and emerging variants.
Article
Biochemical Research Methods
Les Jones, Hemant K. Naikare, Yung-Yi C. Mosley, Ralph A. Tripp
Summary: The study aimed to develop a rapid and sensitive nucleic acid amplification assay for the detection of the novel coronavirus and its variants. The researchers successfully designed a fluorescence-quenched reverse transcription loop-mediated isothermal amplification method, which can detect the virus in clinical samples within a short time and has high sensitivity and specificity.
Review
Virology
Ralph A. Tripp, David E. Martin
Summary: Viral replication and transmissibility are the main causes of endemic and pandemic disease threats. Broad-spectrum antiviral agents are needed. The most common respiratory viruses are coronaviruses, respiratory syncytial viruses, and influenza viruses. Probenecid has been shown to be safe and effective in limiting the replication of influenza A virus and SARS-CoV-2, as well as inhibiting RSV replication in vitro and in vivo.
Article
Virology
Jackelyn Murray, Harrison C. Bergeron, Les P. Jones, Zachary Beau Reener, David E. Martin, Fred D. Sancilio, Ralph A. Tripp
Summary: This study investigated the prophylactic and therapeutic efficacy of probenecid, an FDA-approved drug, in inhibiting RSV replication. The results showed that nanomolar concentrations of probenecid prevented RSV replication in vitro and in vivo, suggesting its potential as a prophylactic and chemotherapeutic agent for RSV.
Article
Chemistry, Medicinal
Brendan T. Freitas, Daniil A. Ahiadorme, Rahul S. Bagul, Ian A. Durie, Samir Ghosh, Jarvis Hill, Naomi E. Kramer, Jackelyn Murray, Brady M. O'Boyle, Emmanuel Onobun, Michael G. Pirrone, Justin D. Shepard, Suzanne Enos, Yagya P. Subedi, Kapil Upadhyaya, Ralph A. Tripp, Brian S. Cummings, David Crich, Scott D. Pegan
Summary: In the past 20 years, both severe acute respiratory syndrome coronavirus-1 and severe acute respiratory syndrome coronavirus-2 have caused zoonotic outbreaks in humans. The PLpro enzyme from a subgroup 2b bat coronavirus has been studied to identify structural features and substrate specificity. Based on this, 30 novel noncovalent inhibitors for subgroup 2b PLpro enzymes were designed, providing new directions for antiviral development against this group of coronaviruses.
ACS INFECTIOUS DISEASES
(2022)
Article
Chemistry, Multidisciplinary
Wandi Zhu, Jaeyoung Park, Thomas Pho, Lai Wei, Chunhong Dong, Joo Kim, Yao Ma, Julie A. Champion, Bao-Zhong Wang
Summary: This study explores the use of a novel type of core/shell protein nanoparticle as a vaccine for influenza virus, with the addition of appropriate adjuvants and finding effective mucosal vaccines to combat respiratory infection. The immune-stimulating complexes (ISCOMs)/monophosphoryl lipid A (MPLA) adjuvants boost the immune responses induced by the protein nanoparticles when administered intramuscularly. Furthermore, intranasal delivery of ISCOMs/MPLA-adjuvanted nanoparticles results in significantly strengthened immune responses and higher levels of antigen-specific antibodies in both systemic and local mucosa.
Article
Virology
Harrison C. Bergeron, Jackelyn Murray, Aakash Arora, Ana M. Nunez M. Castrejon, Rebecca M. DuBois, Larry J. Anderson, Lawrence M. Kauvar, Ralph A. Tripp
Summary: Respiratory syncytial virus (RSV) causes respiratory disease in infants and elderly. Current immune prophylaxis is limited to anti-RSV fusion (F) protein monoclonal antibody (mAb). However, mAbs targeting the attachment (G) protein are necessary to prevent aberrant pathogenic responses. Two high-affinity anti-G protein mAbs, 3D3 and 2D10, have been identified as effective in neutralizing RSV and reducing disease. This study compares the neutralization and immune responses of 3D3, 2D10, and palivizumab in a mouse model of RSV infection.
Review
Immunology
Ralph A. Tripp
Summary: Influenza virus constantly changes, making it difficult to develop immunity through vaccination. Efforts are being made to develop universal vaccines that can protect against various strains of influenza viruses. Understanding the host immune response is crucial for vaccine development.
EXPERT REVIEW OF VACCINES
(2023)
Article
Virology
David E. Martin, Neelam Pandey, Purvi Chavda, Gurpreet Singh, Rakesh Sutariya, Frederic Sancilio, Ralph A. Tripp
Summary: This study suggests that treating symptomatic mild-to-moderate COVID-19 patients with probenecid can significantly decrease the time to viral clearance and result in a higher proportion of complete symptom resolution by day 10.
Article
Immunology
Noopur Bhatnagar, Ki-Hye Kim, Jeeva Subbiah, Sakinah Muhammad-Worsham, Bo Ryoung Park, Rong Liu, Phillip Grovenstein, Bao-Zhong Wang, Sang-Moo Kang
Summary: The study suggests that heterologous prime-boost influenza vaccination strategy is more effective in inducing broader protective immunity compared to repeated vaccination with the same antigen, by increasing strain-specific hemagglutination inhibition titers and high levels of IgG antibodies.
Review
Microbiology
Harrison C. Bergeron, Matthew R. Hansen, Ralph A. Tripp
Summary: This review examines the roles and functions of type I, II, and III IFN responses to respiratory virus infections, as well as the specific IFN responses underlying immunity and protection from disease.
Article
Infectious Diseases
Harrison C. Bergeron, Lawrence M. Kauvar, Ralph A. Tripp
Summary: This study investigates how monoclonal antibodies against the RSV F and G proteins modify the type I and III IFN responses to RSV infection. The findings reveal that an anti-G protein monoclonal antibody improves the protective early antiviral response, which has important implications for vaccine and therapeutic design. This research provides insights into the role of G protein antibodies in improving IFN responses against RSV disease.
THERAPEUTIC ADVANCES IN INFECTIOUS DISEASE
(2023)
Article
Virology
Ralph A. Tripp, David E. Martin
Summary: In the early stages of drug discovery, assays are developed to evaluate the effectiveness of new and known molecular entities, primarily targeting specific features within the virus. However, screening efforts often prioritize finding active antiviral drugs against known viral targets, overlooking drugs that inhibit virus replication by targeting host genes or pathways.
Review
Engineering, Biomedical
Chunhong Dong, Bao-Zhong Wang
Summary: This review highlights the importance and characteristics of next-generation influenza vaccines, as well as the contribution of cutting-edge nanoparticle technology. It provides new insights into the rational design of nanoparticle universal vaccines to combat influenza epidemics and pandemics.
ADVANCED NANOBIOMED RESEARCH
(2022)