Wilma Grönroos, Petri Helenius, Maarit Valtonen, Matti Waris, Olli J. Heinonen, Olli Ruuskanen
Background
Viral acute respiratory infections (ARIs) are an important cause of illness in athletes. However, their impact on ice hockey players is unclear.
Method
We describe an outbreak of ARIs in a professional ice hockey team.
Results
Contrary to expected influenza, the 40-day outbreak was caused by 8 different respiratory viruses, that is, 2 different influenza A viruses, human coronavirus-NL63 (HCoV-NL63), respiratory syncytial viruses (RSV) A and B, 2 different rhinoviruses, enterovirus D68, and parainfluenza type 2 virus.
Conclusion
Only influenza A and HCoV-NL63 were possibly spread within the team thus suggesting an important contraction from the community. The burden of illness was substantial.
{"title":"An Outbreak of Respiratory Viral Infections in a Professional Ice Hockey Team","authors":"Wilma Grönroos, Petri Helenius, Maarit Valtonen, Matti Waris, Olli J. Heinonen, Olli Ruuskanen","doi":"10.1111/irv.70041","DOIUrl":"10.1111/irv.70041","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Viral acute respiratory infections (ARIs) are an important cause of illness in athletes. However, their impact on ice hockey players is unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>We describe an outbreak of ARIs in a professional ice hockey team.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Contrary to expected influenza, the 40-day outbreak was caused by 8 different respiratory viruses, that is, 2 different influenza A viruses, human coronavirus-NL63 (HCoV-NL63), respiratory syncytial viruses (RSV) A and B, 2 different rhinoviruses, enterovirus D68, and parainfluenza type 2 virus.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Only influenza A and HCoV-NL63 were possibly spread within the team thus suggesting an important contraction from the community. The burden of illness was substantial.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13544,"journal":{"name":"Influenza and Other Respiratory Viruses","volume":"18 11","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/irv.70041","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Isabella M. Y. Cheung, Janine Paynter, David Broderick, Adrian Trenholme, Cass A. Byrnes, Cameron C. Grant, S. Qiu Huang, Nikki Turner, Peter McIntyre
Objective
Influenza reemerged after a 2020–2021 hiatus in 2022, but understanding the resurgence needs pre-COVID era surveillance. We compared age- and ethnicity-specific incidence of severe acute respiratory infection (SARI) from a hospital network in Auckland, New Zealand, in 2022 against a baseline, 2012–2019.
Methods
Annual and monthly influenza SARI incidence per 1000 persons by age and ethnic group between 2012 and 2022 was calculated using resident population as the denominator. The hospitals capture most severe illness of the resident population.
Results
Influenza SARI incidence was highest among <1 year olds (2.62; 95% CI: 1.84–3.61) during 2012–2019, lowest at 6–14 years, and did not significantly increase until 50–64 years (0.35; 95% CI: 0.27–0.45), reaching 1.19 (95% CI: 0.57–1.55) in those ≥75 years. In all age groups, incidence was at least threefold higher in Māori and Pacific Peoples. No influenza SARI was identified in 2020–2021. In 2022, despite an early peak, annual incidence (<65 years) was lower than baseline in all ethnic groups, but incidence (≥65 years) in Māori (2.06; 95% CI: 1.22–3.26) and Pacific (3.94; 95% CI: 2.97–5.13) peoples was higher in 2022 than most baseline years, whereas incidence in NMNP (0.22; 95% CI: 0.14–0.32) was lower than any baseline year.
Conclusion
After no influenza 2020–2021, Auckland had an early, high, narrow peak in 2022. Stratification by age and ethnicity revealed striking discrepancies in incidence among Māori and Pacific adults over 65 years compared with NMNP adults, with implications for targeted vaccination strategies.
{"title":"Severe Acute Respiratory Infection (SARI) due to Influenza in Post-COVID Resurgence: Disproportionate Impact on Older Māori and Pacific Peoples","authors":"Isabella M. Y. Cheung, Janine Paynter, David Broderick, Adrian Trenholme, Cass A. Byrnes, Cameron C. Grant, S. Qiu Huang, Nikki Turner, Peter McIntyre","doi":"10.1111/irv.70029","DOIUrl":"10.1111/irv.70029","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Influenza reemerged after a 2020–2021 hiatus in 2022, but understanding the resurgence needs pre-COVID era surveillance. We compared age- and ethnicity-specific incidence of severe acute respiratory infection (SARI) from a hospital network in Auckland, New Zealand, in 2022 against a baseline, 2012–2019.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Annual and monthly influenza SARI incidence per 1000 persons by age and ethnic group between 2012 and 2022 was calculated using resident population as the denominator. The hospitals capture most severe illness of the resident population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Influenza SARI incidence was highest among <1 year olds (2.62; 95% CI: 1.84–3.61) during 2012–2019, lowest at 6–14 years, and did not significantly increase until 50–64 years (0.35; 95% CI: 0.27–0.45), reaching 1.19 (95% CI: 0.57–1.55) in those ≥75 years. In all age groups, incidence was at least threefold higher in Māori and Pacific Peoples. No influenza SARI was identified in 2020–2021. In 2022, despite an early peak, annual incidence (<65 years) was lower than baseline in all ethnic groups, but incidence (≥65 years) in Māori (2.06; 95% CI: 1.22–3.26) and Pacific (3.94; 95% CI: 2.97–5.13) peoples was higher in 2022 than most baseline years, whereas incidence in NMNP (0.22; 95% CI: 0.14–0.32) was lower than any baseline year.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>After no influenza 2020–2021, Auckland had an early, high, narrow peak in 2022. Stratification by age and ethnicity revealed striking discrepancies in incidence among Māori and Pacific adults over 65 years compared with NMNP adults, with implications for targeted vaccination strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13544,"journal":{"name":"Influenza and Other Respiratory Viruses","volume":"18 11","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/irv.70029","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Adjuvants use several mechanisms to boost immunogenicity and to modulate immune response. The strength of adsorption of antigen by adjuvants can be a determinant factor for significant improvement of immunopotentiation.
Methods
We expressed recombinant RBD-FC in PichiaPink Strain 4 and examined the vaccination of mice by vaccine formulation with different adjuvants (sodium alginate and aluminum hydroxide, alone and together).
Results
Sodium alginate significantly increased the immunogenicity and stability of RBD-FC antigen, so RBD-FC formulated with combined alginate and alum (AlSa) and sodium alginate alone showed higher antibody titer and stability. Immunogenicity of RBD-FC:AlSa was determined by serological assays including direct enzyme-linked immunosorbent assay (ELISA) and surrogate virus neutralization test (sVNT). High levels of IgGs and neutralizing antibodies were measured in serum of mice immunized with the RBD-FC:AlSa formulation. On the other hand, cytokines IL-10 and INF-γ were severely accumulated in response to RBD-FC:AlSa, and after 10 days, their accumulation was significantly declined, whereas IL-4 showed the highest and the lowest accumulation in response to alum and alginate, respectively.
Conclusions
Our data may suggest that combination of alum and sodium alginate has a better compatibility with RBD-FC in vaccine formulation.
{"title":"Improvement of RBD-FC Immunogenicity by Using Alum–Sodium Alginate Adjuvant Against SARS-COV-2","authors":"Mahboobeh Dehghan, Hossein Askari, Masoud Tohidfar, Seyed Omid Ranaei Siadat, Fataneh Fatemi","doi":"10.1111/irv.70018","DOIUrl":"10.1111/irv.70018","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Adjuvants use several mechanisms to boost immunogenicity and to modulate immune response. The strength of adsorption of antigen by adjuvants can be a determinant factor for significant improvement of immunopotentiation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We expressed recombinant RBD-FC in PichiaPink Strain 4 and examined the vaccination of mice by vaccine formulation with different adjuvants (sodium alginate and aluminum hydroxide, alone and together).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Sodium alginate significantly increased the immunogenicity and stability of RBD-FC antigen, so RBD-FC formulated with combined alginate and alum (AlSa) and sodium alginate alone showed higher antibody titer and stability. Immunogenicity of RBD-FC:AlSa was determined by serological assays including direct enzyme-linked immunosorbent assay (ELISA) and surrogate virus neutralization test (sVNT). High levels of IgGs and neutralizing antibodies were measured in serum of mice immunized with the RBD-FC:AlSa formulation. On the other hand, cytokines IL-10 and INF-γ were severely accumulated in response to RBD-FC:AlSa, and after 10 days, their accumulation was significantly declined, whereas IL-4 showed the highest and the lowest accumulation in response to alum and alginate, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our data may suggest that combination of alum and sodium alginate has a better compatibility with RBD-FC in vaccine formulation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13544,"journal":{"name":"Influenza and Other Respiratory Viruses","volume":"18 11","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/irv.70018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ajay K. Sethi, Cristalyne Bell, Derek Norton, Maureen D. Goss, Shari Barlow, Guanhua Chen, Amra Uzicanin, Jonathan L. Temte
Background
Household transmission of SARS-CoV-2 is a driver of the ongoing COVID-19 pandemic. Understanding factors that contribute to secondary infection risks (SIRs) can define changing trends and inform public health policies.
Methods
The ORegon CHild Absenteeism due to Respiratory Disease Study (ORCHARDS) prospectively monitors respiratory viruses within the Oregon School District (OSD) in southcentral Wisconsin. Households with students who had ≥ 2 respiratory symptoms were eligible and opted to participate in ORCHARDS. Between October 28, 2020, and May 16, 2022, all household members provided self-collected nasal specimens on days 0, 7, and 14 for SARS-CoV-2 detection using real-time reverse-transcription-polymerase chain reaction. We used logistic regression to investigate individual- and household-level characteristics associated with SARS-CoV-2 transmission.
Results
Overall, 127 households comprising 572 individuals (48% female; 52% male; 0.4% nonbinary; 77% ≥ 18 years) had at least one detection of SARS-CoV-2. The overall SIR was 47% and decreased over time (pre-Delta = 72% [95% CI: 58%–83%]; Delta = 51% [40%–63%]; and Omicron = 41% [36%–47%]). Odds of household transmission were 63% lower during the Omicron period compared with the pre-Delta period (OR = 0.36 [95% CI: 0.13–0.94] p = 0.037). Greater household density (members/bedroom) was significantly associated with household transmission during the Omicron period (OR = 6.8, [2.19–21.37] p = 0.001). Index case age, illness severity, and individual symptoms were not significantly associated with odds of household transmission.
Conclusions
Greater household density was associated with a higher risk of SARS-CoV-2 transmission, but the risk declined over time with subsequent variants. Interplay between variants, prior infection, and individual/household factors may identify modifiable factors (e.g., behavior and vaccination) to reduce future transmission risk.
{"title":"Factors Associated With Transmission Across Three Waves of SARS-CoV-2 in a Prospective Community-Based Study of Households With School-Aged Children—Dane County, Wisconsin, 2020–2022","authors":"Ajay K. Sethi, Cristalyne Bell, Derek Norton, Maureen D. Goss, Shari Barlow, Guanhua Chen, Amra Uzicanin, Jonathan L. Temte","doi":"10.1111/irv.70031","DOIUrl":"10.1111/irv.70031","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Household transmission of SARS-CoV-2 is a driver of the ongoing COVID-19 pandemic. Understanding factors that contribute to secondary infection risks (SIRs) can define changing trends and inform public health policies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The ORegon CHild Absenteeism due to Respiratory Disease Study (ORCHARDS) prospectively monitors respiratory viruses within the Oregon School District (OSD) in southcentral Wisconsin. Households with students who had ≥ 2 respiratory symptoms were eligible and opted to participate in ORCHARDS. Between October 28, 2020, and May 16, 2022, all household members provided self-collected nasal specimens on days 0, 7, and 14 for SARS-CoV-2 detection using real-time reverse-transcription-polymerase chain reaction. We used logistic regression to investigate individual- and household-level characteristics associated with SARS-CoV-2 transmission.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Overall, 127 households comprising 572 individuals (48% female; 52% male; 0.4% nonbinary; 77% ≥ 18 years) had at least one detection of SARS-CoV-2. The overall SIR was 47% and decreased over time (pre-Delta = 72% [95% CI: 58%–83%]; Delta = 51% [40%–63%]; and Omicron = 41% [36%–47%]). Odds of household transmission were 63% lower during the Omicron period compared with the pre-Delta period (OR = 0.36 [95% CI: 0.13–0.94] <i>p</i> = 0.037). Greater household density (members/bedroom) was significantly associated with household transmission during the Omicron period (OR = 6.8, [2.19–21.37] <i>p</i> = 0.001). Index case age, illness severity, and individual symptoms were not significantly associated with odds of household transmission.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Greater household density was associated with a higher risk of SARS-CoV-2 transmission, but the risk declined over time with subsequent variants. Interplay between variants, prior infection, and individual/household factors may identify modifiable factors (e.g., behavior and vaccination) to reduce future transmission risk.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13544,"journal":{"name":"Influenza and Other Respiratory Viruses","volume":"18 11","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/irv.70031","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yan Liu, Jiuyang Xu, Cheng Wei, Yitian Xu, Chen Lyu, Mingzhi Sun, Ying Zheng, Bin Cao
Aims
Influenza virus infection may lead to fatal complications including multi-organ failure and sepsis. The influenza virus was detected in various extra-pulmonary organs in autopsy studies during the 2009 pandemic. However, limited research has been conducted on the presence of viral particle or viral components in the peripheral blood.
Methods and Results
We established a mouse model for severe H1N1 influenza. The bile and blood samples were collected over time and inoculated into embryonated chicken eggs. We detected live influenza virus in bile and blood samples in early infection. Immunofluorescence showed influenza viral components in the liver tissue. No live virus was isolated in the bile in mice intragastrically administered with influenza virus, indicating that the virus was spread from the blood stream. Targeted metabolomics analysis of bile acid and liver tissues showed that a secondary bile acid (3-dehydrocholic acid) was decreased after influenza H1N1 infection. Genes related with fatty acid metabolism and bile secretion pathways were down-regulated in liver after influenza virus infection.
Conclusion
Our study indicated that influenza virus viremia is present in severe influenza, and that the liver is a target organ for influenza viral sepsis.
{"title":"Detection of H1N1 Influenza Virus in the Bile of a Severe Influenza Mouse Model","authors":"Yan Liu, Jiuyang Xu, Cheng Wei, Yitian Xu, Chen Lyu, Mingzhi Sun, Ying Zheng, Bin Cao","doi":"10.1111/irv.70012","DOIUrl":"10.1111/irv.70012","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Influenza virus infection may lead to fatal complications including multi-organ failure and sepsis. The influenza virus was detected in various extra-pulmonary organs in autopsy studies during the 2009 pandemic. However, limited research has been conducted on the presence of viral particle or viral components in the peripheral blood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>We established a mouse model for severe H1N1 influenza. The bile and blood samples were collected over time and inoculated into embryonated chicken eggs. We detected live influenza virus in bile and blood samples in early infection. Immunofluorescence showed influenza viral components in the liver tissue. No live virus was isolated in the bile in mice intragastrically administered with influenza virus, indicating that the virus was spread from the blood stream. Targeted metabolomics analysis of bile acid and liver tissues showed that a secondary bile acid (3-dehydrocholic acid) was decreased after influenza H1N1 infection. Genes related with fatty acid metabolism and bile secretion pathways were down-regulated in liver after influenza virus infection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study indicated that influenza virus viremia is present in severe influenza, and that the liver is a target organ for influenza viral sepsis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13544,"journal":{"name":"Influenza and Other Respiratory Viruses","volume":"18 10","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11502934/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Chelsea Lane, Catherine J. Luke, Joseph Bresee, Vivien G. Dugan, Diane J. Post, Julie Schafer, Paul C. Roberts, David E. Wentworth, Michael G. Ison
On November 13–14, 2023, the National Institute of Allergy and Infectious Diseases (NIAID) in partnership with the Task Force for Global Health, Flu Lab, the Canadian Institutes of Health Research, and the Centers for Disease Control and Prevention convened a meeting on controlled human influenza virus infection model (CHIVIM) studies to review the current research landscape of CHIVIM studies and to generate actionable next steps. Presentations and panel discussions highlighted CHIVIM use cases, regulatory and ethical considerations, innovations, networks and standardization, and the utility of using CHIVIM in vaccine development. This report summarizes the presentations, discussions, key takeaways, and future directions for innovations in CHIVIMs. Experts agreed that CHIVIM studies can be valuable for the study of influenza infection, immune response, and transmission. Furthermore, they may have utility in the development of vaccines and other medical countermeasures; however, the use of CHIVIMs to de-risk clinical development of investigational vaccines should employ a cautious approach. Endpoints in CHIVIM studies should be tailored to the specific use case. CHIVIM studies can provide useful supporting data for vaccine licensure but are not required and do not obviate the need for the conduct of field efficacy trials. Future directions in this field include the continued expansion of capacity to conduct CHIVIM studies, development of a broad panel of challenge viruses and assay reagents and standards that can be shared, streamlining of manufacturing processes, the exploration of targeted delivery of virus to the lower respiratory tract, efforts to more closely replicate natural influenza disease in CHIVIM, alignment on a definition of breadth to facilitate development of more broadly protective/universal vaccine approaches, and continued collaboration between stakeholders.
{"title":"Meeting Report: Controlled Human Influenza Virus Infection Model Studies: Current Status and Future Directions for Innovation","authors":"M. Chelsea Lane, Catherine J. Luke, Joseph Bresee, Vivien G. Dugan, Diane J. Post, Julie Schafer, Paul C. Roberts, David E. Wentworth, Michael G. Ison","doi":"10.1111/irv.13358","DOIUrl":"10.1111/irv.13358","url":null,"abstract":"<p>On November 13–14, 2023, the National Institute of Allergy and Infectious Diseases (NIAID) in partnership with the Task Force for Global Health, Flu Lab, the Canadian Institutes of Health Research, and the Centers for Disease Control and Prevention convened a meeting on controlled human influenza virus infection model (CHIVIM) studies to review the current research landscape of CHIVIM studies and to generate actionable next steps. Presentations and panel discussions highlighted CHIVIM use cases, regulatory and ethical considerations, innovations, networks and standardization, and the utility of using CHIVIM in vaccine development. This report summarizes the presentations, discussions, key takeaways, and future directions for innovations in CHIVIMs. Experts agreed that CHIVIM studies can be valuable for the study of influenza infection, immune response, and transmission. Furthermore, they may have utility in the development of vaccines and other medical countermeasures; however, the use of CHIVIMs to de-risk clinical development of investigational vaccines should employ a cautious approach. Endpoints in CHIVIM studies should be tailored to the specific use case. CHIVIM studies can provide useful supporting data for vaccine licensure but are not required and do not obviate the need for the conduct of field efficacy trials. Future directions in this field include the continued expansion of capacity to conduct CHIVIM studies, development of a broad panel of challenge viruses and assay reagents and standards that can be shared, streamlining of manufacturing processes, the exploration of targeted delivery of virus to the lower respiratory tract, efforts to more closely replicate natural influenza disease in CHIVIM, alignment on a definition of breadth to facilitate development of more broadly protective/universal vaccine approaches, and continued collaboration between stakeholders.</p>","PeriodicalId":13544,"journal":{"name":"Influenza and Other Respiratory Viruses","volume":"18 10","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marcus Odin, Falko Schmeisser, Jackeline Soto, Jerry P. Weir
Background
The potency of inactivated and recombinant influenza vaccines is measured using the single-radial immunodiffusion (SRID) assay. The strain-specific antigen and antibody potency reagents required for the assay are prepared and distributed by regulatory agencies to ensure vaccine standardization, but timely reagent production is always challenging. This poses unique concerns for rapid pandemic responses. Alternative methods have been described for generating strain-specific potency antibody reagents without the need for live influenza virus, but such methods are infrequently used, suggesting the need for additional antigen expression approaches.
Methods
We describe a rapid process using a mammalian expression system to produce recombinant influenza hemagglutinin (rHA). This platform was used to generate rHA from two H5 clade 2.3.4.4 influenza viruses, in both soluble ectodomain or full-length HA forms, and a soluble ectodomain rHA from an influenza H2 virus.
Results
The purified rHAs were used as immunogens to produce HA antibody reagents that were tested for suitability in the SRID assay to accurately measure the potency of inactivated pandemic influenza vaccines. Antibody reagents generated to either ectodomain or full-length rHA worked well in the SRID assay and resulted in vaccine potency values equivalent to those generated with standard reference antibodies.
Conclusions
The results demonstrate that rHA produced from a simple mammalian cell transfection method can be used to generate HA antibody suitable for use in the influenza vaccine SRID potency assay and suggest a practical means by which an extensive library of pandemic reagents can easily be prepared in advance of and during an influenza emergency.
背景：灭活疫苗和重组流感疫苗的效价是通过单径向免疫扩散 (SRID) 试验来测定的。检测所需的毒株特异性抗原和抗体效价试剂由监管机构制备和分发，以确保疫苗标准化，但及时生产试剂始终是一项挑战。这给大流行病的快速反应带来了独特的问题。已有人描述了无需活流感病毒就能生成毒株特异性抗体试剂的替代方法，但这种方法并不常用，这表明需要更多的抗原表达方法：我们介绍了一种利用哺乳动物表达系统生产重组流感血凝素（rHA）的快速方法。结果：纯化的 rHAs 可用于生产流感血凝素：结果：纯化的 rHA 被用作免疫原来生产 HA 抗体试剂，并在 SRID 试验中测试其适用性，以精确测量大流行流感灭活疫苗的效力。在SRID试验中，外结构域或全长rHA产生的抗体试剂效果良好，疫苗效力值与标准参考抗体产生的效力值相当：结果表明，通过简单的哺乳动物细胞转染方法产生的 rHA 可用来生成适合用于流感疫苗 SRID 效力测定的 HA 抗体，并提出了一种实用的方法，可在流感紧急情况发生之前和发生期间轻松地准备大量大流行试剂库。
{"title":"A Rapid Virus-Free Method for Producing Influenza HA Immunogen Needed for Preparation of Influenza Vaccine Potency Antisera Reagents","authors":"Marcus Odin, Falko Schmeisser, Jackeline Soto, Jerry P. Weir","doi":"10.1111/irv.70024","DOIUrl":"10.1111/irv.70024","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The potency of inactivated and recombinant influenza vaccines is measured using the single-radial immunodiffusion (SRID) assay. The strain-specific antigen and antibody potency reagents required for the assay are prepared and distributed by regulatory agencies to ensure vaccine standardization, but timely reagent production is always challenging. This poses unique concerns for rapid pandemic responses. Alternative methods have been described for generating strain-specific potency antibody reagents without the need for live influenza virus, but such methods are infrequently used, suggesting the need for additional antigen expression approaches.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We describe a rapid process using a mammalian expression system to produce recombinant influenza hemagglutinin (rHA). This platform was used to generate rHA from two H5 clade 2.3.4.4 influenza viruses, in both soluble ectodomain or full-length HA forms, and a soluble ectodomain rHA from an influenza H2 virus.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The purified rHAs were used as immunogens to produce HA antibody reagents that were tested for suitability in the SRID assay to accurately measure the potency of inactivated pandemic influenza vaccines. Antibody reagents generated to either ectodomain or full-length rHA worked well in the SRID assay and resulted in vaccine potency values equivalent to those generated with standard reference antibodies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The results demonstrate that rHA produced from a simple mammalian cell transfection method can be used to generate HA antibody suitable for use in the influenza vaccine SRID potency assay and suggest a practical means by which an extensive library of pandemic reagents can easily be prepared in advance of and during an influenza emergency.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13544,"journal":{"name":"Influenza and Other Respiratory Viruses","volume":"18 10","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11497102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142516370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Owen Devine, Huong Pham, Betsy Gunnels, Heather E. Reese, Molly Steele, Alexia Couture, Danielle Iuliano, Darpun Sachdev, Nisha B. Alden, James Meek, Lucy Witt, Patricia A. Ryan, Libby Reeg, Ruth Lynfield, Susan L. Ropp, Grant Barney, Brenda L. Tesini, Eli Shiltz, Melissa Sutton, H. Keipp Talbot, Isabella Reyes, Fiona P. Havers
The COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) was established in March 2020 to monitor trends in hospitalizations associated with SARS-CoV-2 infection. COVID-NET is a geographically diverse population-based surveillance system for laboratory-confirmed COVID-19-associated hospitalizations with a combined catchment area covering approximately 10% of the US population. Data collected in COVID-NET includes monthly counts of hospitalizations for persons with confirmed SARS-CoV-2 infection who reside within the defined catchment area. A Bayesian modeling approach is proposed to estimate US national COVID-associated hospital admission rates based on information reported in the COVID-NET system. A key component of the approach is the ability to estimate uncertainty resulting from extrapolation of hospitalization rates observed within COVID-NET to the US population. In addition, the proposed model enables estimation of other contributors to uncertainty including temporal dependence among reported COVID-NET admission counts, the impact of unmeasured site-specific factors, and the frequency and accuracy of testing for SARS-CoV-2 infection. Based on the proposed model, an estimated 6.3 million (95% uncertainty interval (UI) 5.4–7.3 million) COVID-19-associated hospital admissions occurred in the United States from September 2020 through December 2023. Between April 2020 and December 2023, model-based monthly admission rate estimates ranged from a minimum of 1 per 10,000 population (95% UI 0.7–1.2) in June of 2023 to a highest monthly level of 16 per 10,000 (95% UI 13–19) in January 2022.
{"title":"Extrapolating Sentinel Surveillance Information to Estimate National COVID Hospital Admission Rates: A Bayesian Modeling Approach","authors":"Owen Devine, Huong Pham, Betsy Gunnels, Heather E. Reese, Molly Steele, Alexia Couture, Danielle Iuliano, Darpun Sachdev, Nisha B. Alden, James Meek, Lucy Witt, Patricia A. Ryan, Libby Reeg, Ruth Lynfield, Susan L. Ropp, Grant Barney, Brenda L. Tesini, Eli Shiltz, Melissa Sutton, H. Keipp Talbot, Isabella Reyes, Fiona P. Havers","doi":"10.1111/irv.70026","DOIUrl":"10.1111/irv.70026","url":null,"abstract":"<p>The COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) was established in March 2020 to monitor trends in hospitalizations associated with SARS-CoV-2 infection. COVID-NET is a geographically diverse population-based surveillance system for laboratory-confirmed COVID-19-associated hospitalizations with a combined catchment area covering approximately 10% of the US population. Data collected in COVID-NET includes monthly counts of hospitalizations for persons with confirmed SARS-CoV-2 infection who reside within the defined catchment area. A Bayesian modeling approach is proposed to estimate US national COVID-associated hospital admission rates based on information reported in the COVID-NET system. A key component of the approach is the ability to estimate uncertainty resulting from extrapolation of hospitalization rates observed within COVID-NET to the US population. In addition, the proposed model enables estimation of other contributors to uncertainty including temporal dependence among reported COVID-NET admission counts, the impact of unmeasured site-specific factors, and the frequency and accuracy of testing for SARS-CoV-2 infection. Based on the proposed model, an estimated 6.3 million (95% uncertainty interval (UI) 5.4–7.3 million) COVID-19-associated hospital admissions occurred in the United States from September 2020 through December 2023. Between April 2020 and December 2023, model-based monthly admission rate estimates ranged from a minimum of 1 per 10,000 population (95% UI 0.7–1.2) in June of 2023 to a highest monthly level of 16 per 10,000 (95% UI 13–19) in January 2022.</p>","PeriodicalId":13544,"journal":{"name":"Influenza and Other Respiratory Viruses","volume":"18 10","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11497105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Influenza A viruses pose a significant public health threat globally and are characterized by rapid evolution of the hemagglutinin (HA) gene causing seasonal epidemics. The aim of this study was to investigate the evolutionary dynamics of A(H3N2) circulating in Bhutan during 2022 and 2023.
Methods
We analysed 166 whole-genome sequences of influenza A(H3N2) from Bhutan, obtained from the GISAID database. We employed a Bayesian Markov Chain Monte Carlo (MCMC) framework, with a curated global dataset of HA sequences from regions with significant migration links to Bhutan. Phylogenetic, temporal, and phylogeographic analyses were conducted to elucidate the evolutionary dynamics and spatial dissemination of the viruses.
Results
Our phylogenetic analysis identified the circulation of influenza A(H3N2) Clade 3C.2a1b.2a.2 in Bhutan during 2022 and 2023, with viruses further classified into three subclades: 2a.3 (39/166), 2a.3a.1 (58/166) and 2a.3b (69/166). The TMRCA estimates suggest that these viral lineages originated approximately 1.93 years prior to their detection. Phylogeographic analysis indicates introductions from the United States in 2022 and Australia in 2023. The mean evolutionary rate across all gene segments was calculated to be 4.42 × 10−3 substitutions per site per year (95% HPD: 3.19 × 10−3 to 5.84 × 10−3), with evidence of purifying selection and limited genetic diversity. Furthermore, reassortment events were rare, with an estimated rate of 0.045 events per lineage per year.
Conclusion
Our findings show that primary forces shaping the local evolution of the influenza A(H3N2) in Bhutan are largely stochastic, with only sporadic instances of adaptive change, and thus underscore the importance of continuous surveillance to mitigate the impact of evolving strains.
{"title":"Evolution of Influenza A(H3N2) Viruses in Bhutan for Two Consecutive Years, 2022 and 2023","authors":"Tshering Dorji, Kunzang Dorji, Sonam Gyeltshen","doi":"10.1111/irv.70028","DOIUrl":"10.1111/irv.70028","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Influenza A viruses pose a significant public health threat globally and are characterized by rapid evolution of the hemagglutinin (HA) gene causing seasonal epidemics. The aim of this study was to investigate the evolutionary dynamics of A(H3N2) circulating in Bhutan during 2022 and 2023.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analysed 166 whole-genome sequences of influenza A(H3N2) from Bhutan, obtained from the GISAID database. We employed a Bayesian Markov Chain Monte Carlo (MCMC) framework, with a curated global dataset of HA sequences from regions with significant migration links to Bhutan. Phylogenetic, temporal, and phylogeographic analyses were conducted to elucidate the evolutionary dynamics and spatial dissemination of the viruses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our phylogenetic analysis identified the circulation of influenza A(H3N2) Clade 3C.2a1b.2a.2 in Bhutan during 2022 and 2023, with viruses further classified into three subclades: 2a.3 (39/166), 2a.3a.1 (58/166) and 2a.3b (69/166). The TMRCA estimates suggest that these viral lineages originated approximately 1.93 years prior to their detection. Phylogeographic analysis indicates introductions from the United States in 2022 and Australia in 2023. The mean evolutionary rate across all gene segments was calculated to be 4.42 × 10<sup>−3</sup> substitutions per site per year (95% HPD: 3.19 × 10<sup>−3</sup> to 5.84 × 10<sup>−3</sup>), with evidence of purifying selection and limited genetic diversity. Furthermore, reassortment events were rare, with an estimated rate of 0.045 events per lineage per year.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings show that primary forces shaping the local evolution of the influenza A(H3N2) in Bhutan are largely stochastic, with only sporadic instances of adaptive change, and thus underscore the importance of continuous surveillance to mitigate the impact of evolving strains.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13544,"journal":{"name":"Influenza and Other Respiratory Viruses","volume":"18 10","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11498999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Joanna Waldock, Rebecca J. Cox, Othmar G. Engelhardt, Stephanie Ascough, Albert Osterhaus, Guus F. Rimmelzwaan, Martin Ludlow, John S. Tregoning, Jacqueline U. McDonald, Ursula J. Buchholz, Rienk E. Jeeninga, Charles. Sande, Christopher Chiu
Controlled human infection models (CHIMs) are a critical tool for the understanding of infectious disease progression, characterising immune responses to infection and rapid assessment of vaccines or drug treatments. There is increasing interest in using CHIMs for vaccine development and an obvious need for widely available and fit-for-purpose challenge agents. Inno4Vac is a large European consortium working towards accelerating and de-risking the development of new vaccines, including development of CHIMs for influenza, respiratory syncytial virus and Clostridium difficile. This report (in two parts) summarises a workshop held at the MHRA in 2021, focused on how to select CHIM candidate strains of influenza and respiratory syncytial virus (RSV) based on desirable virus characteristics and which immune assays would provide relevant information for assessing pre-existing and post-infection immune responses and defining correlates of protection. This manuscript (part 2) summarises presentations and discussions centred around RSV CHIMs and immune assays (an additional manuscript summarises influenza CHIM and immune assays: Inno4Vac workshop report Part 1: Controlled human influenza virus infection model (CHIVIM) strain selection and immune assays for CHIVIM studies, November 2021, MHRA, UK).
{"title":"Inno4Vac Workshop Report Part 2: RSV-Controlled Human Infection Model (CHIM) Strain Selection and Immune Assays for RSV CHIM Studies, November 2021, MHRA, UK","authors":"Joanna Waldock, Rebecca J. Cox, Othmar G. Engelhardt, Stephanie Ascough, Albert Osterhaus, Guus F. Rimmelzwaan, Martin Ludlow, John S. Tregoning, Jacqueline U. McDonald, Ursula J. Buchholz, Rienk E. Jeeninga, Charles. Sande, Christopher Chiu","doi":"10.1111/irv.70013","DOIUrl":"10.1111/irv.70013","url":null,"abstract":"<p>Controlled human infection models (CHIMs) are a critical tool for the understanding of infectious disease progression, characterising immune responses to infection and rapid assessment of vaccines or drug treatments. There is increasing interest in using CHIMs for vaccine development and an obvious need for widely available and fit-for-purpose challenge agents. Inno4Vac is a large European consortium working towards accelerating and de-risking the development of new vaccines, including development of CHIMs for influenza, respiratory syncytial virus and <i>Clostridium difficile</i>. This report (in two parts) summarises a workshop held at the MHRA in 2021, focused on how to select CHIM candidate strains of influenza and respiratory syncytial virus (RSV) based on desirable virus characteristics and which immune assays would provide relevant information for assessing pre-existing and post-infection immune responses and defining correlates of protection. This manuscript (part 2) summarises presentations and discussions centred around RSV CHIMs and immune assays (an additional manuscript summarises influenza CHIM and immune assays: Inno4Vac workshop report Part 1: Controlled human influenza virus infection model (CHIVIM) strain selection and immune assays for CHIVIM studies, November 2021, MHRA, UK).</p>","PeriodicalId":13544,"journal":{"name":"Influenza and Other Respiratory Viruses","volume":"18 10","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11497170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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