Article
Virology
Nada Abbadi, Jarrod J. Mousa
Summary: Neuraminidase (NA) is an important surface protein on influenza virions, playing a crucial role in the viral life cycle and being a target of the immune system. Vaccines currently focus on the hemagglutinin (HA) protein, but NA-specific antibodies have shown promise in reducing infection severity. This review summarizes the characteristics of NA, NA-specific antibodies, NA inhibition mechanism, and recent developments in NA-based influenza vaccines.
Article
Cell Biology
Jenna J. Guthmiller, Julianna Han, Lei Li, Alec W. Freyn, Sean T. H. Liu, Olivia Stovicek, Christopher T. Stamper, Haley L. Dugan, Micah E. Tepora, Henry A. Utset, Dalia J. Bitar, Natalie J. Hamel, Siriruk Changrob, Nai-Ying Zheng, Min Huang, Florian Krammer, Raffael Nachbagauer, Peter Palese, Andrew B. Ward, Patrick C. Wilson
Summary: Broadly neutralizing antibodies targeting conserved receptor-binding site (RBS) or lateral patch epitopes of hemagglutinin (HA) are recalled by first exposure to the 2009 pandemic H1N1 influenza virus. Monoclonal antibodies (mAbs) generated against these epitopes exhibit broad neutralizing activity against H1N1 viruses spanning 40 years of viral evolution, providing potent protection in vivo. Antibodies targeting the lateral patch are found to have near universal binding to H1 viruses, while RBS-binding antibodies commonly cross-react with H3N2 viruses and influenza B viruses.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Microbiology
Jing-ying Sun, Chun-yan Guo, Guo-rong Wang, Li-ting Yan, Qing Feng, Yan Li, Xue-ping Huo, Xin Xie, Jun Hu, Li-jun Sun
Summary: Our previous studies found that the H1-50 monoclonal antibody cross-reacts with pancreatic tissue and islet beta-cells, and further investigation revealed that it binds to PHB protein. We screened the binding epitopes using a phage 12-peptide library and identified a specific binding sequence of H1-50 mAb to influenza A virus HA. The study provides new insights into the role of influenza virus in type 1 diabetes.
CURRENT MICROBIOLOGY
(2023)
Article
Multidisciplinary Sciences
Yu-Jen Chang, Cheng-Yun Yeh, Ju-Chien Cheng, Yu-Qi Huang, Kai-Cheng Hsu, Yu-Feng Lin, Chih-Hao Lu
Summary: Eradicating influenza A virus (IAV) is challenging due to its genetic variability. Hemagglutinin (HA) is a promising target for anti-influenza drugs, but its complex structure has hindered structural characterization. Computational analysis identified potential HA inhibitors in the National Cancer Institute database.
SCIENTIFIC REPORTS
(2021)
Article
Immunology
Jeanette Linnea Tingstedt, Christine Stephen, Christian Risinger, Ola Blixt, Vithiagaran Gunalan, Isik Somuncu Johansen, Anders Fomsgaard, Charlotta Polacek, Ria Lassauniere
Summary: Neuraminidase (NA) is an attractive vaccine target as it plays important roles in virus entry and release. In this study, influenza DNA vaccine-induced NA-specific antibodies were evaluated for their inhibition of NA activity and epitope mapping. The antibodies were found to target critical sites of NA, including the enzymatic site and sialic binding site, inhibiting the catalytic activity of NA. New potential antigenic sites were also identified. These findings provide valuable information for rational vaccine design.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Tingting Li, Junyu Chen, Qingbing Zheng, Wenhui Xue, Limin Zhang, Rui Rong, Sibo Zhang, Qian Wang, Minqing Hong, Yuyun Zhang, Lingyan Cui, Maozhou He, Zhen Lu, Zhenyong Zhang, Xin Chi, Jinjin Li, Yang Huang, Hong Wang, Jixian Tang, Dong Ying, Lizhi Zhou, Yingbin Wang, Hai Yu, Jun Zhang, Ying Gu, Yixin Chen, Shaowei Li, Ningshao Xia
Summary: Influenza A viruses are a significant global threat, and this study has identified a chimeric monoclonal antibody, C12H5, that offers broad neutralization against H1N1 and H5N1 viruses. The antibody targets a specific epitope on the surface glycoprotein of the virus, leading to control of virus entry and egress. This discovery could have implications for the development of antiviral drugs and broad-protection vaccines against influenza.
NATURE COMMUNICATIONS
(2022)
Article
Microbiology
Meiling Dai, Wenjuan Du, Carles Martinez-Romero, Tim Leenders, Tom Wennekes, Guus F. Rimmelzwaan, Frank J. M. van Kuppeveld, Ron A. M. Fouchier, Adolfo Garcia-Sastre, Erik de Vries, Cornelis A. M. de Haan
Summary: Research shows that the antigenic and enzymatic properties of the influenza A virus neuraminidase are intertwined, with several residues affecting multiple properties. This entanglement may play a crucial role in the evolution of the neuraminidase.
Review
Immunology
Sarah Creytens, Mirte N. Pascha, Marlies Ballegeer, Xavier Saelens, Cornelis A. M. de Haan
Summary: Neuraminidase of influenza viruses is crucial in the virus life cycle and a key target of the host immune system. Recent research has focused on utilizing neuraminidase to enhance the protective potential of influenza vaccines. Understanding the antigenicity and immune responses of neuraminidase can provide valuable insights for vaccine design and flu control strategies.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Chemistry, Medicinal
Yulia Desheva, Igor Losev, Nadezhda Petkova, Polina Kudar, Svetlana Donina, Andrey Mamontov, Chih-Hsuan Tsai, Yu-Chan Chao
Summary: This study investigated the antigenic properties of neuraminidase (NA) in A/H7N9 influenza viruses, finding that the antibodies induced by different A/H7N9 vaccines did not inhibit the NA of each other. In addition, monoclonal antibodies targeting a specific H7N9 strain showed partial cross-protection against a drift variant of H7N9 in mice.
Article
Immunology
Kelly A. S. da Costa, Joanne Marie M. Del Rosario, Matteo Ferrari, Sneha Vishwanath, Benedikt Asbach, Rebecca Kinsley, Ralf Wagner, Jonathan L. Heeney, George W. Carnell, Nigel J. Temperton
Summary: By using NA pseudoviruses and developing the pELLA assay, we successfully measured neuraminidase inhibition levels in different influenza sera and found that pELLA is more sensitive than the commercially available NA-Fluor(TM). These studies may lead to the design of more potent, longer-lasting, and broader protective vaccines that can be used in a pre-pandemic approach in combination with HA vaccines.
Article
Immunology
Shirin Strohmeier, Fatima Amanat, Juan Manuel Carreno, Florian Krammer
Summary: This study generated murine monoclonal antibodies to the N6 NA and characterized their breadth and antiviral properties. The antibodies exhibited broad reactivity across the American and Eurasian N6 lineages and showed NA inhibition activity, as well as activity in the antibody dependent cellular cytotoxicity reporter assay and neutralization assay. Escape mutant viruses were generated and mutations on the lateral ridge of the NA were found. Variable protection was observed in H4N6 mouse challenge models when the antibodies were given prophylactically.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Fei Wang, Jinsen Wu, Yajuan Wang, Zhimin Wan, Hongxia Shao, Kun Qian, Jianqiang Ye, Aijian Qin
Summary: This study identified key residues on the neuraminidase (NA) of H9N2 virus that are recognized by different monoclonal antibodies (mAbs), shedding light on the antigenic diversity and evolution of H9N2 viruses. These findings contribute to a more comprehensive understanding of the antigenic structure of H9N2 viral NA.
EMERGING MICROBES & INFECTIONS
(2021)
Article
Microbiology
Michael Piepenbrink, Fatai Oladunni, Aitor Nogales, Ahmed M. Khalil, Theresa Fitzgerald, Madhubanti Basu, Christopher Fucile, David J. Topham, Alexander F. Rosenberg, Luis Martinez-Sobrido, James J. Kobie
Summary: Influenza A virus (IAV) infections pose a significant threat to public health due to the variable nature of the virus. This study shows that immunization with a seasonal inactivated influenza vaccine (IIV) can increase the levels of antibodies against H3N2 IAV, a strain known for its genetic drift. These antibodies have broad and potent antiviral activity and can protect against various H3N2 IAV strains. They also persist in the bone marrow, indicating their potential for long-term immunity. These findings contribute to the development of a universal influenza vaccine.
MICROBIOLOGY SPECTRUM
(2023)
Review
Immunology
Madhusudan Rajendran, Florian Krammer, Meagan McMahon
Summary: NA vaccines help reduce disease severity and play a role in preventing viral spread and decreasing viral lung titers. Therefore, incorporating immunogenic forms of NA may become a crucial component of future influenza vaccines.
Article
Immunology
Xuejie Liu, Tianyi Zhao, Liangliang Wang, Zhuolin Yang, Chuming Luo, Minchao Li, Huanle Luo, Caijun Sun, Huacheng Yan, Yuelong Shu
Summary: The study utilized a mosaic vaccine design strategy and genetic algorithms to optimize the influenza virus antigens and generate virus-like particles. Compared to a commercial quadrivalent inactivated influenza vaccine, the mosaic VLPs induced stronger cross-reactive antibody responses, robust T-cell responses, and provided better protection in a mouse model. These findings demonstrate the promising potential of mosaic vaccines for developing a broad influenza vaccine in the future.
Article
Virology
Lauren E. Gentles, Hongquan Wan, Maryna C. Eichelberger, Jesse D. Bloom
Article
Immunology
Ewan P. Plant, Hasmik Manukyan, Jose L. Sanchez, Majid Laassri, Zhiping Ye
Article
Immunology
Hang Xie, Ruoxuan Xiang, Hamilton J. Wan, Ewan P. Plant, Peter Radvak, Martina Kosikova, Xing Li, Olga Zoueva, Zhiping Ye, Xiu-Feng Wan
Summary: The study found that postvaccination antibodies induced by the B/Vic vaccine component of the 2019/20 influenza season had reduced HAI cross-reactivity toward predominant 3DEL viruses in the United States. Specifically, antibodies against the 136E+150K subgroup showed significantly lower titers compared to those against the 136E+150N viruses. Close monitoring of the 3DEL 136E+150K subgroup is recommended should it return and predominate the 2020/21 influenza season.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Microbiology
Jin Gao, Hongquan Wan, Xing Li, Mira Rakic Martinez, Laura Klenow, Yamei Gao, Zhiping Ye, Robert Daniels
Summary: Virions are commonly used as antigen source for viral vaccines, with the antigen abundance determined by the content of each protein in the virus. By exchanging viral backbone internal genes, the NA to HA ratio in virions can be improved to produce vaccines with higher NA content that can elicit more balanced neutralizing antibody responses to NA and HA. This approach could help improve the suboptimal efficacy of current influenza vaccines and provide broader coverage against circulating strains.
Editorial Material
Immunology
Ewan P. Plant, Hang Xie
Article
Genetics & Heredity
Ewan P. Plant, Zhiping Ye
Summary: A new codon-pair bias has been identified in the genomes of different types of influenza virus, with codons having fewer network interactions being more frequently paired together. This shared feature among three different influenza types suggests an evolutionary bias, which can impact protein translation speed and RNA structure. This newly identified bias may provide insight into drivers of virus evolution.
FRONTIERS IN GENETICS
(2021)
Article
Virology
Jin Gao, Laura Klenow, Lisa Parsons, Tahir Malik, Je-Nie Phue, Zhizeng Gao, Stephen G. Withers, John Cipollo, Robert Daniels, Hongquan Wan
Summary: This study compared several rNAs produced by the baculovirus/insect cell system with different tetramerization motifs and NA domains, and found that the combination of tetramerization and NA domains significantly impacts the biochemical, immunogenic, and protective properties of the rNAs. Single-dose immunizations were shown to be more informative for evaluating the immune response and protective efficacy of rNAs.
JOURNAL OF VIROLOGY
(2021)
Article
Multidisciplinary Sciences
Ewan P. Plant, Zhiping Ye
Summary: Genomes of different sizes and complexity can be compared using common features and genetic code biases. By grouping codon pairs based on the GC content of the first two nucleotide positions, patterns in nucleotide usage at the third position can be revealed. Differences in biases occur when the second codon has both strong or weak nucleotides, indicating preferences based on interactions between codons, anticodons, tRNAs, and the ribosome. This approach enables comparison of genomes with different size and nucleotide composition, unveiling previously undescribed patterns.
SCIENTIFIC REPORTS
(2022)
Article
Immunology
Jin Gao, Xing Li, Laura Klenow, Tahir Malik, Hongquan Wan, Zhiping Ye, Robert Daniels
Summary: This study compared the antigenicity of neuraminidase (NA) antigens from recent influenza vaccine strains and circulating viruses. The results showed that NAs from circulating H1N1 viruses and vaccine strains for the 2017-2021 seasons are antigenically similar but distinct from the previous H1N1 strain. Changes in N1 antigenicity were attributed to accumulated substitutions over time. NAs from circulating H3N2 viruses and the 2020-2021 vaccine strains showed similar antigenicity but varied across different seasons.
Article
Biochemistry & Molecular Biology
Laura Klenow, Rageia Elfageih, Jin Gao, Hongquan Wan, Stephen G. Withers, Jan-Willem de Gier, Robert Daniels
Summary: Influenza A viruses and pneumococci both express neuraminidases that catalyze release of sialic acid residues. The enzymatic properties of neuraminidases from both pathogens were compared, and it was found that they have evolved similar yet distinct strategies to optimize their catalytic activity.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Daniel Stadlbauer, Meagan McMahon, Hannah L. Turner, Xueyong Zhu, Hongquan Wan, Juan Manuel Carreno, George O'Dell, Shirin Strohmeier, Zain Khalil, Marta Luksza, Harm van Bakel, Viviana Simon, Ali H. Ellebedy, Ian A. Wilson, Andrew B. Ward, Florian Krammer
Summary: The H3N2 influenza viruses circulating since 2016 have acquired a glycosylation site in the neuraminidase near the active site. However, this glycosylation does not significantly impact the binding and function of broadly reactive monoclonal antibodies.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Weichun Tang, Hang Xie, Zhiping Ye, Angelia A. Eick-Cost, Mark Scheckelhoff, Courtney E. Gustin, Jay H. Bream, Ewan P. Plant
Summary: Levels of cytokines were compared in post-vaccination sera of young adults who experienced breakthrough influenza infections. Both inactivated and live attenuated influenza vaccines resulted in lower levels of IL-8. IIV vaccination led to higher antibody levels and lower IFN-gamma levels compared to LAIV vaccination. The status of the immune system following vaccination is crucial for successful vaccination and subsequent protection against disease.
SCIENTIFIC REPORTS
(2023)
Article
Multidisciplinary Sciences
Hyung-Joon Kwon, Martina Kosikova, Weichun Tang, Uriel Ortega-Rodriguez, Peter Radvak, Ruoxuan Xiang, Kelly E. Mercer, Levan Muskhelishvili, Kelly Davis, Jerrold M. Ward, Ivan Kosik, Jaroslav Holly, Insung Kang, Jonathan W. Yewdell, Ewan P. Plant, Wilbur H. Chen, Mallory C. Shriver, Robin S. Barnes, Marcela F. Pasetti, Bin Zhou, David E. Wentworth, Hang Xe
Summary: In this study, we investigated the factors contributing to breakthrough infections of SARS-CoV-2 in a K18-hACE2 transgenic mouse model. We found that the Delta and closely related Kappa variants caused viral pneumonia and severe lung lesions in K18-hACE2 mice. Post-vaccination sera from humans after the 2nd dose of COVID-19 mRNA vaccines showed significantly lower neutralizing efficiency against Delta/Kappa compared to the early 614G virus both in vitro and in vivo. Five months after vaccination, more than 50% of donors lacked detectable neutralizing antibodies against Delta and Kappa, and all mice that received post-vaccination sera from 5 months post-vaccination died after lethal challenges. Although a third vaccine dose could enhance antibody neutralization against Delta in vitro and in vivo, the mean log neutralization titers against the latest Omicron subvariants were only 1/3-1/2 of those against the original 614D virus.
Article
Biochemistry & Molecular Biology
Lisa M. Parsons, Olga Zoueva, Gabrielle Grubbs, Ewan Plant, Ewa Jankowska, Yijia Xie, Hao Song, George F. Gao, Zhiping Ye, Surender Khurana, John F. Cipollo
Summary: Recent studies have shown that group 1 influenza A viruses (IAV) containing specific hemagglutinins (HAs) are resistant to lung surfactant protein D (SP-D). However, group 2 IAV, specifically H3 viruses, have high affinity for SP-D due to the presence of high-mannose glycans. This information is important for understanding the potential pandemic risk of these strains.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Virology
Xing Li, Zhiping Ye, Ewan P. Plant
Summary: By analyzing clinical and cultured samples using the same bioinformatic pipeline, it was found that 5' copyback DVGs are prevalent in human clinical samples but not in cultured samples. Furthermore, there are differences in DVG production and composition between in vivo and in vitro infections.