Pub Date : 2024-09-17DOI: 10.1038/s41541-024-00959-0
Joseph P. Casazza, Amelia R. Hofstetter, Pamela J. M. Costner, LaSonji A. Holman, Cynthia S. Hendel, Alicia T. Widge, Richard L. Wu, William R. Whalen, Jennifer Cunningham, Anita Arthur, Xiaolin Wang, Abidemi Ola, Jamie Saunders, Floreliz Mendoza, Laura Novik, Maria C. Burgos Florez, Ana M. Ortega-Villa, Preeti J. Apte, Larisa Strom, Lu Wang, Marjaan Imam, Manjula Basappa, Mursal Naisan, Mike Castro, Jessica F. Trost, Sandeep R. Narpala, Hillary A. Vanderven, Galina V. Yamshchikov, Nina M. Berkowitz, Ingelise J. Gordon, Sarah H. Plummer, Diane L. Wycuff, Sandra Vazquez, Rebecca A. Gillespie, Adrian Creanga, William C. Adams, Kevin Carlton, Jason G. Gall, Adrian B. McDermott, Leonid A. Serebryannyy, Katherine V. Houser, Richard A. Koup, Barney S. Graham, Julie E. Ledgerwood, John R. Mascola, Theodore C. Pierson, Sarah F. Andrews, Masaru Kanekiyo, Lesia K. Dropulic
The relative conservation of the influenza hemagglutinin (HA) stem compared to that of the immunodominant HA head makes the HA stem an attractive target for broadly protective influenza vaccines. Here we report the first-in-human, dose-escalation, open-label trial (NCT04579250) evaluating an unadjuvanted group 2 stabilized stem ferritin nanoparticle vaccine based on the H10 A/Jiangxi-Donghu/346/2013 influenza HA, H10ssF, in healthy adults. Participants received a single 20 mcg dose (n = 3) or two 60 mcg doses 16 weeks apart (n = 22). Vaccination with H10ssF was safe and well tolerated with only mild systemic and local reactogenicity reported. No serious adverse events occurred. Vaccination significantly increased homologous H10 HA stem binding and neutralizing antibodies at 2 weeks after both first and second vaccinations, and these responses remained above baseline at 40 weeks. Heterologous H3 and H7 binding antibodies also significantly increased after each vaccination and remained elevated throughout the study. These data indicate that the group 2 HA stem nanoparticle vaccine is safe and induces stem-directed binding and neutralizing antibodies.
{"title":"Phase 1 dose-escalation trial evaluating a group 2 influenza hemagglutinin stabilized stem nanoparticle vaccine","authors":"Joseph P. Casazza, Amelia R. Hofstetter, Pamela J. M. Costner, LaSonji A. Holman, Cynthia S. Hendel, Alicia T. Widge, Richard L. Wu, William R. Whalen, Jennifer Cunningham, Anita Arthur, Xiaolin Wang, Abidemi Ola, Jamie Saunders, Floreliz Mendoza, Laura Novik, Maria C. Burgos Florez, Ana M. Ortega-Villa, Preeti J. Apte, Larisa Strom, Lu Wang, Marjaan Imam, Manjula Basappa, Mursal Naisan, Mike Castro, Jessica F. Trost, Sandeep R. Narpala, Hillary A. Vanderven, Galina V. Yamshchikov, Nina M. Berkowitz, Ingelise J. Gordon, Sarah H. Plummer, Diane L. Wycuff, Sandra Vazquez, Rebecca A. Gillespie, Adrian Creanga, William C. Adams, Kevin Carlton, Jason G. Gall, Adrian B. McDermott, Leonid A. Serebryannyy, Katherine V. Houser, Richard A. Koup, Barney S. Graham, Julie E. Ledgerwood, John R. Mascola, Theodore C. Pierson, Sarah F. Andrews, Masaru Kanekiyo, Lesia K. Dropulic","doi":"10.1038/s41541-024-00959-0","DOIUrl":"https://doi.org/10.1038/s41541-024-00959-0","url":null,"abstract":"<p>The relative conservation of the influenza hemagglutinin (HA) stem compared to that of the immunodominant HA head makes the HA stem an attractive target for broadly protective influenza vaccines. Here we report the first-in-human, dose-escalation, open-label trial (NCT04579250) evaluating an unadjuvanted group 2 stabilized stem ferritin nanoparticle vaccine based on the H10 A/Jiangxi-Donghu/346/2013 influenza HA, H10ssF, in healthy adults. Participants received a single 20 mcg dose (<i>n</i> = 3) or two 60 mcg doses 16 weeks apart (<i>n</i> = 22). Vaccination with H10ssF was safe and well tolerated with only mild systemic and local reactogenicity reported. No serious adverse events occurred. Vaccination significantly increased homologous H10 HA stem binding and neutralizing antibodies at 2 weeks after both first and second vaccinations, and these responses remained above baseline at 40 weeks. Heterologous H3 and H7 binding antibodies also significantly increased after each vaccination and remained elevated throughout the study. These data indicate that the group 2 HA stem nanoparticle vaccine is safe and induces stem-directed binding and neutralizing antibodies.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142261034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Developing broad-spectrum influenza vaccines is crucial for influenza control and potential pandemic preparedness. Here, we reported a novel vaccine design utilizing circular RNA (circRNA) as a delivery platform for multi-subtype neuraminidases (NA) (influenza A N1, N2, and influenza B Victoria lineage NA) immunogens. Individual NA circRNA lipid nanoparticles (LNP) elicited robust NA-specific antibody responses with neuraminidase inhibition activity (NAI), preventing the virus from egressing and infecting neighboring cells. Additionally, the administration of circRNA LNP induced cellular immunity in mice. To achieve a universal influenza vaccine, we combined all three subtypes of NA circRNA-LNPs to generate a trivalent circRNA vaccine. The trivalent vaccine elicited a balanced antibody response against all three NA subtypes and a Th1-biased immune response in mice. Moreover, it protected mice against the lethal challenge of matched and mismatched H1N1, H3N2, and influenza B viruses, encompassing circulating and ancestral influenza virus strains. This study highlights the potential of delivering multiple NA antigens through circRNA-LNPs as a promising strategy for effectively developing a universal influenza vaccine against diverse influenza viruses.
开发广谱流感疫苗对于流感控制和潜在的大流行防备至关重要。在此,我们报告了一种新型疫苗设计,利用环状 RNA(circRNA)作为多亚型神经氨酸酶(NA)(甲型 N1、N2 和乙型 Victoria 系 NA 流感病毒)免疫原的递送平台。单个NA circRNA脂质纳米颗粒(LNP)可激发具有神经氨酸酶抑制活性(NAI)的强NA特异性抗体反应,阻止病毒外逸并感染邻近细胞。此外,给小鼠注射 circRNA LNP 还能诱导细胞免疫。为了获得通用流感疫苗,我们将所有三种亚型的 NA circRNA-LNPs 结合在一起,制成了三价 circRNA 疫苗。三价疫苗能引起小鼠对所有三种 NA 亚型的平衡抗体反应和 Th1 偏向的免疫反应。此外,它还能保护小鼠免受匹配和不匹配的 H1N1、H3N2 和 B 型流感病毒(包括流行的和祖先的流感病毒株)的致命挑战。这项研究凸显了通过 circRNA-LNPs 提供多种 NA 抗原的潜力,是有效开发针对不同流感病毒的通用流感疫苗的可行策略。
{"title":"CircRNA based multivalent neuraminidase vaccine induces broad protection against influenza viruses in mice","authors":"Xinyu Yue, Cailing Zhong, Rui Cao, Sizhe Liu, Zhiran Qin, Lin Liu, Yanmei Zhai, Wanyu Luo, Yikai Lian, Mengjie Zhang, Hongjie Lu, Yuanyuan Wang, Mengxin Xu, Shuning Liu, Kexin Lv, Yuzhu Sun, Xingchen Zhu, Haoting Mai, Jing Liao, Jingyi Yang, Lei Deng, Yang Liu, Caijun Sun, Ke-Wei Zheng, Yuelong Shu, Yao-Qing Chen","doi":"10.1038/s41541-024-00963-4","DOIUrl":"https://doi.org/10.1038/s41541-024-00963-4","url":null,"abstract":"<p>Developing broad-spectrum influenza vaccines is crucial for influenza control and potential pandemic preparedness. Here, we reported a novel vaccine design utilizing circular RNA (circRNA) as a delivery platform for multi-subtype neuraminidases (NA) (influenza A N1, N2, and influenza B Victoria lineage NA) immunogens. Individual NA circRNA lipid nanoparticles (LNP) elicited robust NA-specific antibody responses with neuraminidase inhibition activity (NAI), preventing the virus from egressing and infecting neighboring cells. Additionally, the administration of circRNA LNP induced cellular immunity in mice. To achieve a universal influenza vaccine, we combined all three subtypes of NA circRNA-LNPs to generate a trivalent circRNA vaccine. The trivalent vaccine elicited a balanced antibody response against all three NA subtypes and a Th1-biased immune response in mice. Moreover, it protected mice against the lethal challenge of matched and mismatched H1N1, H3N2, and influenza B viruses, encompassing circulating and ancestral influenza virus strains. This study highlights the potential of delivering multiple NA antigens through circRNA-LNPs as a promising strategy for effectively developing a universal influenza vaccine against diverse influenza viruses.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142261029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-16DOI: 10.1038/s41541-024-00952-7
Raveen Rathnasinghe, Lauren A. Chang, Rebecca Pearl, Sonia Jangra, Amy Aspelund, Alaura Hoag, Soner Yildiz, Ignacio Mena, Weina Sun, Madhumathi Loganathan, Nicholas Alexander Crossland, Hans P. Gertje, Anna Elise Tseng, Sadaf Aslam, Randy A. Albrecht, Peter Palese, Florian Krammer, Michael Schotsaert, Thomas Muster, Adolfo García-Sastre
Influenza viruses pose a threat to public health as evidenced by severe morbidity and mortality in humans on a yearly basis. Given the constant changes in the viral glycoproteins owing to antigenic drift, seasonal influenza vaccines need to be updated periodically and effectiveness often drops due to mismatches between vaccine and circulating strains. In addition, seasonal influenza vaccines are not protective against antigenically shifted influenza viruses with pandemic potential. Here, we have developed a highly immunogenic vaccination regimen based on live-attenuated influenza vaccines (LAIVs) comprised of an attenuated virus backbone lacking non-structural protein 1 (ΔNS1), the primary host interferon antagonist of influenza viruses, with chimeric hemagglutinins (cHA) composed of exotic avian head domains with a highly conserved stalk domain, to redirect the humoral response towards the HA stalk. In this study, we showed that cHA-LAIV vaccines induce robust serum and mucosal responses against group 1 stalk and confer antibody-dependent cell cytotoxicity activity. Mice that intranasally received cH8/1-ΔNS1 followed by a cH11/1-ΔNS1 heterologous booster had robust humoral responses for influenza A virus group 1 HAs and were protected from seasonal H1N1 influenza virus and heterologous highly pathogenic avian H5N1 lethal challenges. When compared with mice immunized with the standard of care or cold-adapted cHA-LAIV, cHA-ΔNS1 immunized mice had robust antigen-specific CD8+ T-cell responses which also correlated with markedly reduced lung pathology post-challenge. These observations support the development of a trivalent universal influenza vaccine for the protection against group 1 and group 2 influenza A viruses and influenza B viruses.
{"title":"Sequential immunization with chimeric hemagglutinin ΔNS1 attenuated influenza vaccines induces broad humoral and cellular immunity","authors":"Raveen Rathnasinghe, Lauren A. Chang, Rebecca Pearl, Sonia Jangra, Amy Aspelund, Alaura Hoag, Soner Yildiz, Ignacio Mena, Weina Sun, Madhumathi Loganathan, Nicholas Alexander Crossland, Hans P. Gertje, Anna Elise Tseng, Sadaf Aslam, Randy A. Albrecht, Peter Palese, Florian Krammer, Michael Schotsaert, Thomas Muster, Adolfo García-Sastre","doi":"10.1038/s41541-024-00952-7","DOIUrl":"https://doi.org/10.1038/s41541-024-00952-7","url":null,"abstract":"<p>Influenza viruses pose a threat to public health as evidenced by severe morbidity and mortality in humans on a yearly basis. Given the constant changes in the viral glycoproteins owing to antigenic drift, seasonal influenza vaccines need to be updated periodically and effectiveness often drops due to mismatches between vaccine and circulating strains. In addition, seasonal influenza vaccines are not protective against antigenically shifted influenza viruses with pandemic potential. Here, we have developed a highly immunogenic vaccination regimen based on live-attenuated influenza vaccines (LAIVs) comprised of an attenuated virus backbone lacking non-structural protein 1 (ΔNS1), the primary host interferon antagonist of influenza viruses, with chimeric hemagglutinins (cHA) composed of exotic avian head domains with a highly conserved stalk domain, to redirect the humoral response towards the HA stalk. In this study, we showed that cHA-LAIV vaccines induce robust serum and mucosal responses against group 1 stalk and confer antibody-dependent cell cytotoxicity activity. Mice that intranasally received cH8/1-ΔNS1 followed by a cH11/1-ΔNS1 heterologous booster had robust humoral responses for influenza A virus group 1 HAs and were protected from seasonal H1N1 influenza virus and heterologous highly pathogenic avian H5N1 lethal challenges. When compared with mice immunized with the standard of care or cold-adapted cHA-LAIV, cHA-ΔNS1 immunized mice had robust antigen-specific CD8<sup>+</sup> T-cell responses which also correlated with markedly reduced lung pathology post-challenge. These observations support the development of a trivalent universal influenza vaccine for the protection against group 1 and group 2 influenza A viruses and influenza B viruses.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142261026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-14DOI: 10.1038/s41541-024-00962-5
Lisa Singh, Le Bao, Leticia Bode, Ceren Budak, Josh Pasek, Trivellore Raghunathan, Michael Traugott, Yanchen Wang, Nathan Wycoff
Anti-vaccine sentiment during the COVID-19 pandemic grew at an alarming rate, leaving much to understand about the relationship between people’s vaccination status and the information they were exposed to. This study investigated the relationship between vaccine behavior, decision rationales, and information exposure on social media over time. Using a cohort study that consisted of a nationally representative survey of American adults, three subpopulations (early adopters, late adopters, and nonadopters) were analyzed through a combination of statistical analysis, network analysis, and semi-supervised topic modeling. The main reasons Americans reported choosing to get vaccinated were safety and health. However, work requirements and travel were more important for late adopters than early adopters (95% CI on OR of [0.121, 0.453]). While late adopters’ and nonadopters’ primary reason for not getting vaccinated was it being too early, late adopters also mentioned safety issues more often and nonadopters mentioned government distrust (95% CI on OR of [0.125, 0.763]). Among those who shared Twitter/X accounts, early adopters and nonadopters followed a larger fraction of highly partisan political accounts compared to late adopters, and late adopters were exposed to more neutral and pro-vaccine messaging than nonadopters. Together, these findings suggest that the decision-making process and the information environments of these subpopulations have notable differences, and any online vaccination campaigns need to consider these differences when attempting to provide accurate vaccine information to all three subpopulations.
在 COVID-19 大流行期间,反疫苗情绪以惊人的速度增长,人们的疫苗接种状况与他们所接触到的信息之间的关系还有待进一步了解。本研究调查了疫苗接种行为、决策依据和在社交媒体上接触信息的时间之间的关系。该研究采用了一项具有全国代表性的美国成年人调查,通过统计分析、网络分析和半监督主题建模相结合的方法,对三个亚群(早期接种者、晚期接种者和非接种者)进行了分析。据报告,美国人选择接种疫苗的主要原因是安全和健康。然而,与早期采用者相比,工作要求和旅行对晚期采用者更为重要(OR 的 95% CI 为 [0.121, 0.453])。虽然晚接种者和未接种者不接种疫苗的主要原因是接种时间太早,但晚接种者也更常提到安全问题,而未接种者则提到对政府的不信任(OR 的 95% CI 为 [0.125, 0.763])。在分享 Twitter/X 账户的人群中,早期接种者和未接种者比晚期接种者关注了更多党派色彩浓厚的政治账户,而晚期接种者比未接种者接触了更多中立和支持疫苗的信息。这些发现共同表明,这些亚人群的决策过程和信息环境存在明显差异,任何在线疫苗接种活动在试图向所有三个亚人群提供准确的疫苗信息时都需要考虑这些差异。
{"title":"Understanding the rationales and information environments for early, late, and nonadopters of the COVID-19 vaccine","authors":"Lisa Singh, Le Bao, Leticia Bode, Ceren Budak, Josh Pasek, Trivellore Raghunathan, Michael Traugott, Yanchen Wang, Nathan Wycoff","doi":"10.1038/s41541-024-00962-5","DOIUrl":"https://doi.org/10.1038/s41541-024-00962-5","url":null,"abstract":"<p>Anti-vaccine sentiment during the COVID-19 pandemic grew at an alarming rate, leaving much to understand about the relationship between people’s vaccination status and the information they were exposed to. This study investigated the relationship between vaccine behavior, decision rationales, and information exposure on social media over time. Using a cohort study that consisted of a nationally representative survey of American adults, three subpopulations (early adopters, late adopters, and nonadopters) were analyzed through a combination of statistical analysis, network analysis, and semi-supervised topic modeling. The main reasons Americans reported choosing to get vaccinated were safety and health. However, work requirements and travel were more important for late adopters than early adopters (95% CI on OR of [0.121, 0.453]). While late adopters’ and nonadopters’ primary reason for not getting vaccinated was it being too early, late adopters also mentioned safety issues more often and nonadopters mentioned government distrust (95% CI on OR of [0.125, 0.763]). Among those who shared Twitter/X accounts, early adopters and nonadopters followed a larger fraction of highly partisan political accounts compared to late adopters, and late adopters were exposed to more neutral and pro-vaccine messaging than nonadopters. Together, these findings suggest that the decision-making process and the information environments of these subpopulations have notable differences, and any online vaccination campaigns need to consider these differences when attempting to provide accurate vaccine information to all three subpopulations.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142261031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-14DOI: 10.1038/s41541-024-00951-8
Kamil Fuławka, Ralph Hertwig, Thorsten Pachur
Vaccine hesitancy was a major challenge during the COVID-19 pandemic. A common but sometimes ineffective intervention to reduce vaccine hesitancy involves providing information on vaccine effectiveness, side effects, and related probabilities. Could biased processing of this information contribute to vaccine refusal? We examined the information inspection of 1200 U.S. participants with anti-vaccination, neutral, or pro-vaccination attitudes before they stated their willingness to accept eight different COVID-19 vaccines. All participants—particularly those who were anti-vaccination—frequently ignored some of the information. This deliberate ignorance, especially toward probabilities of extreme side effects, was a stronger predictor of vaccine refusal than typically investigated demographic variables. Computational modeling suggested that vaccine refusals among anti-vaccination participants were driven by ignoring even inspected information. In the neutral and pro-vaccination groups, vaccine refusal was driven by distorted processing of side effects and their probabilities. Our findings highlight the necessity for interventions tailored to individual information-processing tendencies.
{"title":"COVID-19 vaccine refusal is driven by deliberate ignorance and cognitive distortions","authors":"Kamil Fuławka, Ralph Hertwig, Thorsten Pachur","doi":"10.1038/s41541-024-00951-8","DOIUrl":"https://doi.org/10.1038/s41541-024-00951-8","url":null,"abstract":"<p>Vaccine hesitancy was a major challenge during the COVID-19 pandemic. A common but sometimes ineffective intervention to reduce vaccine hesitancy involves providing information on vaccine effectiveness, side effects, and related probabilities. Could biased processing of this information contribute to vaccine refusal? We examined the information inspection of 1200 U.S. participants with anti-vaccination, neutral, or pro-vaccination attitudes before they stated their willingness to accept eight different COVID-19 vaccines. All participants—particularly those who were anti-vaccination—frequently ignored some of the information. This deliberate ignorance, especially toward probabilities of extreme side effects, was a stronger predictor of vaccine refusal than typically investigated demographic variables. Computational modeling suggested that vaccine refusals among anti-vaccination participants were driven by ignoring even inspected information. In the neutral and pro-vaccination groups, vaccine refusal was driven by distorted processing of side effects and their probabilities. Our findings highlight the necessity for interventions tailored to individual information-processing tendencies.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142261030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-13DOI: 10.1038/s41541-024-00960-7
Huong N. Q. Tran, Malcolm Risk, Girish B. Nair, Lili Zhao
We compared the risks and benefits of COVID-19 vaccines using a causal pathway analysis to weigh up possible risk factors of thromboembolic events post-vaccination. The self-controlled case series (SCCS) method examined the association between thromboembolic events and vaccination while a case-control study assessed the association between thromboembolic events and COVID-19, addressing under-reported infection data issues. The net vaccine effect was estimated using results from SCCS and case-control studies. We used electronic health record data from Corewell Health (16,640 subjects in SCCS and 106,143 in case-control). We found increased risks of thromboembolic events post-vaccination (incidence rate ratio: 1.19, 95% CI: [1.08, 1.31] after the first dose; 1.22, 95% CI: [1.11, 1.34] after the second dose). Vaccination attenuated infection-associated thromboembolic risks (odds ratio: 4.65, 95% CI: [4.18, 5.17] in unvaccinated vs 2.77, 95% CI: [2.40, 3.24] in vaccinated). After accounting for vaccine efficacy and protection against infection-associated thromboembolic events, vaccination decreases thromboembolic event risk, especially during high infection rate periods.
{"title":"Risk benefit analysis to evaluate risk of thromboembolic events after mRNA COVID-19 vaccination and COVID-19","authors":"Huong N. Q. Tran, Malcolm Risk, Girish B. Nair, Lili Zhao","doi":"10.1038/s41541-024-00960-7","DOIUrl":"https://doi.org/10.1038/s41541-024-00960-7","url":null,"abstract":"<p>We compared the risks and benefits of COVID-19 vaccines using a causal pathway analysis to weigh up possible risk factors of thromboembolic events post-vaccination. The self-controlled case series (SCCS) method examined the association between thromboembolic events and vaccination while a case-control study assessed the association between thromboembolic events and COVID-19, addressing under-reported infection data issues. The net vaccine effect was estimated using results from SCCS and case-control studies. We used electronic health record data from Corewell Health (16,640 subjects in SCCS and 106,143 in case-control). We found increased risks of thromboembolic events post-vaccination (incidence rate ratio: 1.19, 95% CI: [1.08, 1.31] after the first dose; 1.22, 95% CI: [1.11, 1.34] after the second dose). Vaccination attenuated infection-associated thromboembolic risks (odds ratio: 4.65, 95% CI: [4.18, 5.17] in unvaccinated vs 2.77, 95% CI: [2.40, 3.24] in vaccinated). After accounting for vaccine efficacy and protection against infection-associated thromboembolic events, vaccination decreases thromboembolic event risk, especially during high infection rate periods.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142261032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-10DOI: 10.1038/s41541-024-00949-2
Troy J. Kemp, Gitika Panicker, Carina Eklund, Jianhui Nie, Youchun Wang, Simon Beddows, Peter Rigsby, Weijin Huang, Joakim Dillner, Elizabeth R. Unger, Ligia A. Pinto, Dianna E. Wilkinson
Previously established World Health Organization (WHO) International Standards (IS) for anti-HPV16 and HPV18 antibodies are used to harmonize results across human papillomavirus (HPV) serology assays. Here, we present an international collaborative study to establish ISs for antibodies against HPV6 (NIBSC code 19/298), HPV11 (20/174), HPV31 (20/176), HPV33 (19/290), HPV45 (20/178), HPV52 (19/296) and HPV58 (19/300). The candidate standards were prepared using sera from naturally infected individuals. Each candidate was shown to be monospecific for reactivity against its indicated HPV type except for the HPV11 candidate, which was also reactive against other types. Expression of antibody levels relative to the relevant candidate IS reduced inter-laboratory variation allowing greater comparability between laboratories. Based on these results, the WHO Expert Committee on Biological Standardization established each of the 7 candidates as the 1st IS for antiserum to its indicated HPV type for use in the standardization of HPV pseudovirion-based neutralization and antibody-binding assays.
{"title":"WHO International Standards for antibodies to HPV6 HPV11 HPV31 HPV33 HPV45 HPV52 and HPV58","authors":"Troy J. Kemp, Gitika Panicker, Carina Eklund, Jianhui Nie, Youchun Wang, Simon Beddows, Peter Rigsby, Weijin Huang, Joakim Dillner, Elizabeth R. Unger, Ligia A. Pinto, Dianna E. Wilkinson","doi":"10.1038/s41541-024-00949-2","DOIUrl":"https://doi.org/10.1038/s41541-024-00949-2","url":null,"abstract":"<p>Previously established World Health Organization (WHO) International Standards (IS) for anti-HPV16 and HPV18 antibodies are used to harmonize results across human papillomavirus (HPV) serology assays. Here, we present an international collaborative study to establish ISs for antibodies against HPV6 (NIBSC code 19/298), HPV11 (20/174), HPV31 (20/176), HPV33 (19/290), HPV45 (20/178), HPV52 (19/296) and HPV58 (19/300). The candidate standards were prepared using sera from naturally infected individuals. Each candidate was shown to be monospecific for reactivity against its indicated HPV type except for the HPV11 candidate, which was also reactive against other types. Expression of antibody levels relative to the relevant candidate IS reduced inter-laboratory variation allowing greater comparability between laboratories. Based on these results, the WHO Expert Committee on Biological Standardization established each of the 7 candidates as the 1st IS for antiserum to its indicated HPV type for use in the standardization of HPV pseudovirion-based neutralization and antibody-binding assays.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142227908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-09DOI: 10.1038/s41541-024-00950-9
Sneha Vishwanath, George William Carnell, Martina Billmeier, Luis Ohlendorf, Patrick Neckermann, Benedikt Asbach, Charlotte George, Maria Suau Sans, Andrew Chan, Joey Olivier, Angalee Nadesalingam, Sebastian Einhauser, Nigel Temperton, Diego Cantoni, Joe Grove, Ingo Jordan, Volker Sandig, Paul Tonks, Johannes Geiger, Christian Dohmen, Verena Mummert, Anne Rosalind Samuel, Christian Plank, Rebecca Kinsley, Ralf Wagner, Jonathan Luke Heeney
Updates of SARS-CoV-2 vaccines are required to generate immunity in the population against constantly evolving SARS-CoV-2 variants of concerns (VOCs). Here we describe three novel in-silico designed spike-based antigens capable of inducing neutralising antibodies across a spectrum of SARS-CoV-2 VOCs. Three sets of antigens utilising pre-Delta (T2_32), and post-Gamma sequence data (T2_35 and T2_36) were designed. T2_32 elicited superior neutralising responses against VOCs compared to the Wuhan-1 spike antigen in DNA prime-boost immunisation regime in guinea pigs. Heterologous boosting with the attenuated poxvirus - Modified vaccinia Ankara expressing T2_32 induced broader neutralising immune responses in all primed animals. T2_32, T2_35 and T2_36 elicited broader neutralising capacity compared to the Omicron BA.1 spike antigen administered by mRNA immunisation in mice. These findings demonstrate the utility of structure-informed computationally derived modifications of spike-based antigens for inducing broad immune responses covering more than 2 years of evolved SARS-CoV-2 variants.
{"title":"Computationally designed Spike antigens induce neutralising responses against the breadth of SARS-COV-2 variants","authors":"Sneha Vishwanath, George William Carnell, Martina Billmeier, Luis Ohlendorf, Patrick Neckermann, Benedikt Asbach, Charlotte George, Maria Suau Sans, Andrew Chan, Joey Olivier, Angalee Nadesalingam, Sebastian Einhauser, Nigel Temperton, Diego Cantoni, Joe Grove, Ingo Jordan, Volker Sandig, Paul Tonks, Johannes Geiger, Christian Dohmen, Verena Mummert, Anne Rosalind Samuel, Christian Plank, Rebecca Kinsley, Ralf Wagner, Jonathan Luke Heeney","doi":"10.1038/s41541-024-00950-9","DOIUrl":"https://doi.org/10.1038/s41541-024-00950-9","url":null,"abstract":"<p>Updates of SARS-CoV-2 vaccines are required to generate immunity in the population against constantly evolving SARS-CoV-2 variants of concerns (VOCs). Here we describe three novel in-silico designed spike-based antigens capable of inducing neutralising antibodies across a spectrum of SARS-CoV-2 VOCs. Three sets of antigens utilising pre-Delta (T2_32), and post-Gamma sequence data (T2_35 and T2_36) were designed. T2_32 elicited superior neutralising responses against VOCs compared to the Wuhan-1 spike antigen in DNA prime-boost immunisation regime in guinea pigs. Heterologous boosting with the attenuated poxvirus - Modified vaccinia Ankara expressing T2_32 induced broader neutralising immune responses in all primed animals. T2_32, T2_35 and T2_36 elicited broader neutralising capacity compared to the Omicron BA.1 spike antigen administered by mRNA immunisation in mice. These findings demonstrate the utility of structure-informed computationally derived modifications of spike-based antigens for inducing broad immune responses covering more than 2 years of evolved SARS-CoV-2 variants.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142227862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-07DOI: 10.1038/s41541-024-00955-4
Evelyn Tay, Michael Dymock, Laura Lopez, Catherine Glover, Yuanfei Anny Huang, K Shuvo Bakar, Thomas Snelling, Julie A Marsh, Yue Wu
Community perception of vaccine safety influences vaccine uptake. Our objective was to assess current vaccine safety monitoring by examining factors that may influence the availability of post-vaccination survey data, and thereby the specificity and sensitivity of existing signal detection methods. We used causal directed acyclic graphs (DAGs) and a Bayesian posterior predictive analysis (PPA) signal detection method to understand biological and behavioural factors which may influence signal detection. The DAGs informed the data simulated for scenarios in which these factors were varied. The influence of biological factors such as severity of adverse reactions and behavioural factors such as healthcare-seeking behaviour upon survey participation was found to drive signal detection. Where there was a low prevalence of moderate to severe reactions, false signals were detected when there was a strong influence of reaction severity on both survey participation and seeking medical attention. These findings provide implications for future vaccine safety monitoring.
{"title":"Applying causal inference and Bayesian statistics to understanding vaccine safety signals using a simulation study.","authors":"Evelyn Tay, Michael Dymock, Laura Lopez, Catherine Glover, Yuanfei Anny Huang, K Shuvo Bakar, Thomas Snelling, Julie A Marsh, Yue Wu","doi":"10.1038/s41541-024-00955-4","DOIUrl":"10.1038/s41541-024-00955-4","url":null,"abstract":"<p><p>Community perception of vaccine safety influences vaccine uptake. Our objective was to assess current vaccine safety monitoring by examining factors that may influence the availability of post-vaccination survey data, and thereby the specificity and sensitivity of existing signal detection methods. We used causal directed acyclic graphs (DAGs) and a Bayesian posterior predictive analysis (PPA) signal detection method to understand biological and behavioural factors which may influence signal detection. The DAGs informed the data simulated for scenarios in which these factors were varied. The influence of biological factors such as severity of adverse reactions and behavioural factors such as healthcare-seeking behaviour upon survey participation was found to drive signal detection. Where there was a low prevalence of moderate to severe reactions, false signals were detected when there was a strong influence of reaction severity on both survey participation and seeking medical attention. These findings provide implications for future vaccine safety monitoring.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11380659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}