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The induction of a specific antibody response has long been accepted as a serological hallmark of recent infection or antigen exposure. Much of our understanding of the influenza antibody response has been derived from studying antibodies that target the hemagglutinin (HA) protein. However, growing evidence points to limitations associated with this approach. In this review, we aim to highlight the issue of antibody non-responsiveness after influenza virus infection and vaccination. We will then provide an overview of the major factors known to influence antibody responsiveness to influenza after infection and vaccination. We discuss the biological factors such as age, sex, influence of prior immunity, genetics, and some chronic infections that may affect the induction of influenza antibody responses. We also discuss the technical factors, such as assay choices, strain variations, and viral properties that may influence the sensitivity of the assays used to measure influenza antibodies. Understanding these factors will hopefully provide a more comprehensive picture of what influenza immunogenicity and protection means, which will be important in our effort to improve influenza vaccines.
Xia Lin; Fangmei Lin; Tingting Liang; Mariette Ducatez; Mark Zanin; Sook-San Wong. Antibody Responsiveness to Influenza: What Drives It? Viruses 2021, 13, 1400 .
AMA StyleXia Lin, Fangmei Lin, Tingting Liang, Mariette Ducatez, Mark Zanin, Sook-San Wong. Antibody Responsiveness to Influenza: What Drives It? Viruses. 2021; 13 (7):1400.
Chicago/Turabian StyleXia Lin; Fangmei Lin; Tingting Liang; Mariette Ducatez; Mark Zanin; Sook-San Wong. 2021. "Antibody Responsiveness to Influenza: What Drives It?" Viruses 13, no. 7: 1400.
Summary The failure to mount an antibody response following viral infection or seroconversion failure is a largely underappreciated and poorly understood phenomenon. Here, we identified immunologic markers associated with robust antibody responses after influenza virus infection in two independent human cohorts, SHIVERS and FLU09, based in Auckland, New Zealand and Memphis, Tennessee, USA, respectively. In the SHIVERS cohort, seroconversion significantly associates with (1) hospitalization, (2) greater numbers of proliferating, activated CD4+ T cells, but not CD8+ T cells, in the periphery during the acute phase of illness, and (3) fewer inflammatory monocytes (CD14hiCD16+) by convalescence. In the FLU09 cohort, fewer CD14hiCD16+ monocytes during early illness in the nasal mucosa were also associated with the generation of influenza-specific mucosal immunoglobulin A (IgA) and IgG antibodies. Our study demonstrates that seroconversion failure after infection is a definable immunological phenomenon, associated with quantifiable cellular markers that can be used to improve diagnostics, vaccine efficacy, and epidemiologic efforts.
Sook-San Wong; Christine M. Oshansky; Xi-Zhi J. Guo; Jacqui Ralston; Timothy Wood; Gary E. Reynolds; Ruth Seeds; Lauren Jelley; Ben Waite; Trushar Jeevan; Mark Zanin; Marc-Alain Widdowson; Q. Sue Huang; Paul G. Thomas; Richard J. Webby; Nikki Turner; Michael Baker; Cameron Grant; Colin McArthur; Sally Roberts; Adrian Trenholmes; Conroy Wong; Susan Taylor; Mark Thompson; Diane Gross; Jazmin Duque; Kathryn Haven; Debbie Aley; Pamela Muponisi; Bhamita Chand; Yan Chen; Laurel Plewes; Frann Sawtell; Shirley Lawrence; Reniza Cogcoy; Jo Smith; Franie Gravidez; Mandy Ma; Shona Chamberlin; Kirstin Davey; Tania Knowles; Jo-Ann McLeish; Angela Todd; Judy Bocacao; Wendy Gunn; Pamela Kawakami; Susan Walker; Robyn Madge; Nicole Moore; Fahimeh Rahnama; Helen Qiao; Fifi Tse; Mahtab Zibaei; Tirzah Korrapadu; Louise Optland; Cecilia Dela Cruz. Activated CD4+ T cells and CD14hiCD16+ monocytes correlate with antibody response following influenza virus infection in humans. Cell Reports Medicine 2021, 2, 100237 .
AMA StyleSook-San Wong, Christine M. Oshansky, Xi-Zhi J. Guo, Jacqui Ralston, Timothy Wood, Gary E. Reynolds, Ruth Seeds, Lauren Jelley, Ben Waite, Trushar Jeevan, Mark Zanin, Marc-Alain Widdowson, Q. Sue Huang, Paul G. Thomas, Richard J. Webby, Nikki Turner, Michael Baker, Cameron Grant, Colin McArthur, Sally Roberts, Adrian Trenholmes, Conroy Wong, Susan Taylor, Mark Thompson, Diane Gross, Jazmin Duque, Kathryn Haven, Debbie Aley, Pamela Muponisi, Bhamita Chand, Yan Chen, Laurel Plewes, Frann Sawtell, Shirley Lawrence, Reniza Cogcoy, Jo Smith, Franie Gravidez, Mandy Ma, Shona Chamberlin, Kirstin Davey, Tania Knowles, Jo-Ann McLeish, Angela Todd, Judy Bocacao, Wendy Gunn, Pamela Kawakami, Susan Walker, Robyn Madge, Nicole Moore, Fahimeh Rahnama, Helen Qiao, Fifi Tse, Mahtab Zibaei, Tirzah Korrapadu, Louise Optland, Cecilia Dela Cruz. Activated CD4+ T cells and CD14hiCD16+ monocytes correlate with antibody response following influenza virus infection in humans. Cell Reports Medicine. 2021; 2 (4):100237.
Chicago/Turabian StyleSook-San Wong; Christine M. Oshansky; Xi-Zhi J. Guo; Jacqui Ralston; Timothy Wood; Gary E. Reynolds; Ruth Seeds; Lauren Jelley; Ben Waite; Trushar Jeevan; Mark Zanin; Marc-Alain Widdowson; Q. Sue Huang; Paul G. Thomas; Richard J. Webby; Nikki Turner; Michael Baker; Cameron Grant; Colin McArthur; Sally Roberts; Adrian Trenholmes; Conroy Wong; Susan Taylor; Mark Thompson; Diane Gross; Jazmin Duque; Kathryn Haven; Debbie Aley; Pamela Muponisi; Bhamita Chand; Yan Chen; Laurel Plewes; Frann Sawtell; Shirley Lawrence; Reniza Cogcoy; Jo Smith; Franie Gravidez; Mandy Ma; Shona Chamberlin; Kirstin Davey; Tania Knowles; Jo-Ann McLeish; Angela Todd; Judy Bocacao; Wendy Gunn; Pamela Kawakami; Susan Walker; Robyn Madge; Nicole Moore; Fahimeh Rahnama; Helen Qiao; Fifi Tse; Mahtab Zibaei; Tirzah Korrapadu; Louise Optland; Cecilia Dela Cruz. 2021. "Activated CD4+ T cells and CD14hiCD16+ monocytes correlate with antibody response following influenza virus infection in humans." Cell Reports Medicine 2, no. 4: 100237.
Hemagglutinin and neuraminidase, which constitute the glycoprotein spikes expressed on the surface of influenza A and B viruses, are the most exposed parts of the virus and play critical roles in the viral lifecycle. As such, they make prominent targets for the immune response and antiviral drugs. Neuraminidase inhibitors, particularly oseltamivir, constitute the most commonly used antivirals against influenza viruses, and they have proved their clinical utility against seasonal and emerging influenza viruses. However, the emergence of resistant strains remains a constant threat and consideration. Antivirals targeting the hemagglutinin protein are relatively new and have yet to gain global use but are proving to be effective additions to the antiviral repertoire, with a relatively high threshold for the emergence of resistance. Here we review antiviral drugs, both approved for clinical use and under investigation, that target the influenza virus hemagglutinin and neuraminidase proteins, focusing on their mechanisms of action and the emergence of resistance to them.
Yaqin Bai; Jeremy Jones; Sook-San Wong; Mark Zanin. Antivirals Targeting the Surface Glycoproteins of Influenza Virus: Mechanisms of Action and Resistance. Viruses 2021, 13, 624 .
AMA StyleYaqin Bai, Jeremy Jones, Sook-San Wong, Mark Zanin. Antivirals Targeting the Surface Glycoproteins of Influenza Virus: Mechanisms of Action and Resistance. Viruses. 2021; 13 (4):624.
Chicago/Turabian StyleYaqin Bai; Jeremy Jones; Sook-San Wong; Mark Zanin. 2021. "Antivirals Targeting the Surface Glycoproteins of Influenza Virus: Mechanisms of Action and Resistance." Viruses 13, no. 4: 624.
To inform seroepidemiological studies, we characterized the IgG‐ responses in COVID‐19 patients against the two major SARS‐CoV‐2 viral proteins, spike (S) and nucleocapsid (N). We tested 70 COVID‐19 sera collected up to 85 days post‐symptom onset and 230 non‐COVID‐19 sera, including 27 SARS sera from 2003. Although the average SARS‐CoV‐2 S and N‐IgG titers were comparable, N‐responses were more variable among individuals. S‐ and N‐assay specificity tested with non‐COVID‐19 sera were comparable at 97.5% and 97.0%, respectively. Therefore, S will make a better target due to its lower cross‐reactive potential and its' more consistent frequency of detection compared to N.
Cheng Xiao; Shiman Ling; Minshan Qiu; Zhenxuan Deng; Liping Chen; Airu Zhu; Yi Chen; Yong Liu; Xia Lin; Fangmei Lin; Qiubao Wu; Lihan Shen; Feng Ye; Xiaoqing Liu; Yimin Li; Jincun Zhao; Zifeng Yang; Benjamin J. Cowling; Richard Webby; Mark Zanin; Sook‐San Wong. Human post‐infection serological response to the spike and nucleocapsid proteins of SARS‐CoV‐2. Influenza and Other Respiratory Viruses 2020, 15, 7 -12.
AMA StyleCheng Xiao, Shiman Ling, Minshan Qiu, Zhenxuan Deng, Liping Chen, Airu Zhu, Yi Chen, Yong Liu, Xia Lin, Fangmei Lin, Qiubao Wu, Lihan Shen, Feng Ye, Xiaoqing Liu, Yimin Li, Jincun Zhao, Zifeng Yang, Benjamin J. Cowling, Richard Webby, Mark Zanin, Sook‐San Wong. Human post‐infection serological response to the spike and nucleocapsid proteins of SARS‐CoV‐2. Influenza and Other Respiratory Viruses. 2020; 15 (1):7-12.
Chicago/Turabian StyleCheng Xiao; Shiman Ling; Minshan Qiu; Zhenxuan Deng; Liping Chen; Airu Zhu; Yi Chen; Yong Liu; Xia Lin; Fangmei Lin; Qiubao Wu; Lihan Shen; Feng Ye; Xiaoqing Liu; Yimin Li; Jincun Zhao; Zifeng Yang; Benjamin J. Cowling; Richard Webby; Mark Zanin; Sook‐San Wong. 2020. "Human post‐infection serological response to the spike and nucleocapsid proteins of SARS‐CoV‐2." Influenza and Other Respiratory Viruses 15, no. 1: 7-12.
The public health response to the COVID-19 outbreak in mainland China: a narrative review
Mark Zanin; Cheng Xiao; Tingting Liang; Shiman Ling; Fengming Zhao; Zhenting Huang; Fangmei Lin; Xia Lin; Zhanpeng Jiang; Sook-San Wong. The public health response to the COVID-19 outbreak in mainland China: a narrative review. Journal of Thoracic Disease 2020, 12, 4434 -4449.
AMA StyleMark Zanin, Cheng Xiao, Tingting Liang, Shiman Ling, Fengming Zhao, Zhenting Huang, Fangmei Lin, Xia Lin, Zhanpeng Jiang, Sook-San Wong. The public health response to the COVID-19 outbreak in mainland China: a narrative review. Journal of Thoracic Disease. 2020; 12 (8):4434-4449.
Chicago/Turabian StyleMark Zanin; Cheng Xiao; Tingting Liang; Shiman Ling; Fengming Zhao; Zhenting Huang; Fangmei Lin; Xia Lin; Zhanpeng Jiang; Sook-San Wong. 2020. "The public health response to the COVID-19 outbreak in mainland China: a narrative review." Journal of Thoracic Disease 12, no. 8: 4434-4449.
Background Severe COVID‐19 patients typically test positive for SARS‐CoV‐2 RNA for extended periods of time, even after recovery from severe disease. Due to the timeframe involved, these patients may have developed humoral immunity to SARS‐CoV‐2 while still testing positive for viral RNA in swabs. Data are lacking on exposure risks in these situations. Here, we studied SARS‐CoV‐2 environmental contamination in an ICU and an isolation ward caring for such COVID‐19 patients. Methods We collected air and surface samples in a hospital caring for critical and severe COVID‐19 cases from common areas and areas proximal to patients. Results Of the 218 ICU samples, an air sample contained SARS‐CoV‐2 RNA. Of the 182 isolation ward samples, nine contained SARS‐CoV‐2 RNA. These were collected from a facemask, the floor, mobile phones, and the air in the patient room and bathroom. Serum antibodies against SARS‐CoV‐2 were detected in these patients at the beginning of the study. Conclusions While there is a perception of increased risk in the ICU, our study demonstrates that isolation wards may pose greater risks to healthcare workers and exposure risks remain with clinically improved patients, weeks after their initial diagnoses. As these patients had serum antibodies, further studies may be warranted to study the utility of serum antibodies as a surrogate of viral clearance in allowing people to return to work. We recommend continued vigilance even with patients who appear to have recovered from COVID‐19.
Hui Lei; Feng Ye; Xiaoqing Liu; Zhenting Huang; Shiman Ling; Zhanpeng Jiang; Jing Cheng; Xiaoqun Huang; Qiubao Wu; Shiguan Wu; Yanmin Xie; Cheng Xiao; Dan Ye; Zifeng Yang; Yimin Li; Nancy H. L. Leung; Benjamin J. Cowling; Jianxing He; Sook‐San Wong; Mark Zanin. SARS‐CoV‐2 environmental contamination associated with persistently infected COVID‐19 patients. Influenza and Other Respiratory Viruses 2020, 14, 688 -699.
AMA StyleHui Lei, Feng Ye, Xiaoqing Liu, Zhenting Huang, Shiman Ling, Zhanpeng Jiang, Jing Cheng, Xiaoqun Huang, Qiubao Wu, Shiguan Wu, Yanmin Xie, Cheng Xiao, Dan Ye, Zifeng Yang, Yimin Li, Nancy H. L. Leung, Benjamin J. Cowling, Jianxing He, Sook‐San Wong, Mark Zanin. SARS‐CoV‐2 environmental contamination associated with persistently infected COVID‐19 patients. Influenza and Other Respiratory Viruses. 2020; 14 (6):688-699.
Chicago/Turabian StyleHui Lei; Feng Ye; Xiaoqing Liu; Zhenting Huang; Shiman Ling; Zhanpeng Jiang; Jing Cheng; Xiaoqun Huang; Qiubao Wu; Shiguan Wu; Yanmin Xie; Cheng Xiao; Dan Ye; Zifeng Yang; Yimin Li; Nancy H. L. Leung; Benjamin J. Cowling; Jianxing He; Sook‐San Wong; Mark Zanin. 2020. "SARS‐CoV‐2 environmental contamination associated with persistently infected COVID‐19 patients." Influenza and Other Respiratory Viruses 14, no. 6: 688-699.
Influenza B virus is a main causative pathogen of annual influenza epidemics, however, research on influenza B virus in general lags behind that on influenza A viruses, one of the important reasons is studies on influenza B viruses in animal models are limited. Here we investigated the tree shrew as a potential model for influenza B virus studies. Tree shrews and ferrets were inoculated with either a Yamagata or Victoria lineage influenza B virus. Symptoms including nasal discharge and weight loss were observed. Nasal wash and respiratory tissues were collected at 2, 4 and 6 days post inoculation (DPI). Viral titers were measured in nasal washes and tissues were used for pathological examination and extraction of mRNA for measurement of cytokine expression. Clinical signs and pathological changes were also evident in the respiratory tracts of tree shrews and ferrets. Although nasal symptoms including sneezing and rhinorrhea were evident in ferrets infected with influenza B virus, tree shrews showed no significant respiratory symptoms, only milder nasal secretions appeared. Weight loss was observed in tree shrews but not ferrets. V0215 and Y12 replicated in all three animal (ferrets, tree shrews and mice) models with peak titers evident on 2DPI. There were no significant differences in peak viral titers in ferrets and tree shrews inoculated with Y12 at 2 and 4DPI, but viral titers were detected at 6DPI in tree shrews. Tree shrews infected with influenza B virus showed similar seroconversion and respiratory tract pathology to ferrets. Elevated levels of cytokines were detected in the tissues isolated from the respiratory tract after infection with either V0215 or Y12 compared to the levels in the uninfected control in both animals. Overall, the tree shrew was sensitive to infection and disease by influenza B virus. The tree shrew to be a promising model for influenza B virus research.
Bing Yuan; Chunguang Yang; Xueshan Xia; Mark Zanin; Sook-San Wong; Fan Yang; Jixiang Chang; Zhitong Mai; Jin Zhao; Yunhui Zhang; Runfeng Li; Nanshan Zhong; Zifeng Yang. The tree shrew is a promising model for the study of influenza B virus infection. Virology Journal 2019, 16, 77 .
AMA StyleBing Yuan, Chunguang Yang, Xueshan Xia, Mark Zanin, Sook-San Wong, Fan Yang, Jixiang Chang, Zhitong Mai, Jin Zhao, Yunhui Zhang, Runfeng Li, Nanshan Zhong, Zifeng Yang. The tree shrew is a promising model for the study of influenza B virus infection. Virology Journal. 2019; 16 (1):77.
Chicago/Turabian StyleBing Yuan; Chunguang Yang; Xueshan Xia; Mark Zanin; Sook-San Wong; Fan Yang; Jixiang Chang; Zhitong Mai; Jin Zhao; Yunhui Zhang; Runfeng Li; Nanshan Zhong; Zifeng Yang. 2019. "The tree shrew is a promising model for the study of influenza B virus infection." Virology Journal 16, no. 1: 77.