COVID-19 Serosurveys and Vaccine Study Site Preparations

COVID-19 血清调查和疫苗研究现场准备

• 批准号: 10692220
• 负责人: Patrick Duffy
• 金额: $ 39.04万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10692220
• 关键词: 2019-nCoV; Acute; Address; Affect; Africa; Africa South of the Sahara; Age; Antibodies; Antibody Response; Antigens; Antimalarials; Binding Proteins; Biological Assay; COVID-19; COVID-19 impact; COVID-19 pandemic; COVID-19 severity; COVID-19 vaccine; Cambodian; Carrier Proteins; Clinical; Clinical Trials; Collaborations; Communicable Diseases; Communities; Confidence Intervals; Emerging Communicable Diseases; Enzyme-Linked Immunosorbent Assay; Epidemiology; Exposure to; Future; Goals; Health; Holly; Household; Immune Sera; Immunoglobulin G; Immunology; Incidence; Individual; Infection; Journals; Literature; Longitudinal cohort; Malaria; Mali; Measures; Monitor; Outcome; Parasitemia; Participant; Penetration; Performance; Phase; Plasmodium falciparum; Population; Population Surveillance; Postpartum Women; Pregnant Women; Preparation; Prevalence; Proteins; Publications; Reagent; Recombinants; Reporting; Rural; Rural Population; SARS-CoV-2 antigen; SARS-CoV-2 spike protein; SARS-CoV-2 transmission; SARS-CoV-2 variant; Sampling; Seasons; Sentinel; Serology; Serology test; Seroprevalences; Site; Specificity; Subgroup; Suspensions; Target Populations; Technology; Testing; Tropical Disease; United States; Urban Population; Vaccines; Variant; Viral; Virus; Zoonoses; betacoronavirus; experience; frontier; immunogenicity; improved; low and middle-income countries; malaria transmission; nonhuman primate; pandemic disease; pathogen; performance tests; programs; receptor binding; response; seroconversion; seropositive; serosurveillance; serosurvey; transmission process; vaccine candidate; vaccine platform; vaccine trial; viral detection

In July 2020, we commenced a community COVID-19 seroprevalence study at existing clinical trials sites in Mali. This study is a Public Health Surveillance Activity in collaboration with the Ministry of Health in Mali to describe the sero-epidemiology of COVID-19 in urban and rural populations. Using the demographic and clinical information collected from participants, we will describe the age-stratified seroprevalence and fraction of asymptomatic/pauci-symptomatic cases to help understand the penetration of SARS-CoV-2 into the community. Additional exploratory objectives to understand viral carriage, locally circulating variants, and improve direct virus detection at study sites have been added to help enhance local capacity for Public Health surveillance and possible future clinical trials. Separately, we have leveraged our in-house vaccine platforms to develop COVID-19 vaccine candidates that may be suitable for use in low/middle income countries like Mali. From our publications this year, we report the following advances in FY2022: Woodford J, Sagara I, Diawara H, Assadou M, Katile A, Attaher O, Issiaka D, Santara G Soumbounou I, Traore S, Traore M, Dicko O, Niambele S, Mahamar A, Kamate B, Haidara B, Sissoko K, Sankare S, Diarra S, Zeguime A, Doritchamou J, Zaidi I, Dicko A, Duffy PE. Recent malaria does not substantially impact COVID-19 antibody response or rates of symptomatic illness in communities with high malaria and COVID-19 transmission in Mali, West Africa. 2022. Frontiers in Immunology. Aug 3. Malaria has been hypothesized as a factor that may have reduced the severity of the COVID-19 pandemic in sub-Saharan Africa. To evaluate the effect of recent malaria on COVID-19, we assessed a subgroup of individuals participating in a longitudinal cohort COVID-19 serosurvey that were also undergoing intensive malaria monitoring as part of antimalarial vaccine trials during the 2020 transmission season in Mali. These communities experienced a high incidence of primarily asymptomatic or mild COVID-19 during 2020 and 2021. In 1314 individuals, 711 had intercurrent parasitemia; 442 were symptomatic with clinical malaria and 269 had asymptomatic parasitemia. Intercurrent parasitemia was not associated with new COVID-19 seroconversion (29.7% (211/711) vs. 30.0% (181/603), p=0.9038) or with rates of reported symptomatic seroconversion during the malaria transmission season. In the subsequent dry season, prior parasitemia was not associated with new COVID-19 seroconversion (22.0% (133/605) vs. 22.1% (108/488), p>0.9999), with symptomatic seroconversion, or with reversion from seropositive to seronegative (prior parasitemia: 36.2% (64/177) vs. no parasitemia: 30.1% (37/119), p=0.3842). After excluding participants with asymptomatic parasitemia, clinical malaria was also not associated with COVID-19 serostatus or symptomatic seroconversion when compared to participants with no parasitemia during the monitoring period. In communities with intense seasonal malaria and a high incidence of asymptomatic or mild COVID-19, we did not demonstrate a relationship between recent malaria and subsequent response to COVID-19. Lifetime exposure, rather than recent infection, may be responsible for any effect of malaria on COVID-19 severity. Woodford J, Sagara I, Kwan JL, Zaidi I, Dicko A, Duffy PE. Assessing and minimizing the effect of malaria on SARS-CoV-2 serodiagnostics. 2021. Frontiers in Tropical Diseases. Dec 13. Malaria may affect the reliability of SARS-CoV-2 seroassay performance and limit understanding of SARS-CoV-2 epidemiology in malaria-endemic regions. We presented our experience conducting SARS-CoV-2 serosurveillance in seasonal malaria-affected communities in Mali and discuss relevant literature regarding the effect of malaria on the performance of SARS-CoV-2 serodiagnostics, including approaches to minimize the effect of malaria-associated assay interference. Woodford J, Sagara I, Dicko A, Zeguime A, Doucoure M, Kwan J, Zaidi I, Doritchamou JYA, Snow-Smith M, Alani N, Renn JP, Kosik I, Holly J, Yewdell J, Esposito D, Sadtler K, Duffy PE. SARS-CoV-2 seroassay performance and optimization in a population with high background reactivity in Mali. 2021. Journal of Infectious Diseases. Oct 6. False positivity may hinder the utility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological tests in sub-Saharan Africa. From 312 Malian samples collected before 2020, we measured antibodies to the commonly tested SARS-CoV-2 antigens and 4 other betacoronaviruses by enzyme-linked immunosorbent assay (ELISA). In a subset of samples, we assessed antibodies to a panel of P. falciparum antigens by suspension bead array and functional antiviral activity by SARS-CoV-2 pseudovirus neutralization assay. We then evaluated the performance of an ELISA using SARS-CoV-2 spike protein and receptor-binding domain developed in the United States using Malian positive and negative control samples. To optimize test performance, we compared single- and 2-antigen approaches using existing assay cutoffs and population-specific cutoffs. Background reactivity to SARS-CoV-2 antigens was common in prepandemic Malian samples. The SARS-CoV-2 reactivity varied between communities, increased with age, and correlated negligibly/weakly with other betacoronavirus and P. falciparum antibodies. No pre-pandemic samples demonstrated functional activity. Regardless of the cutoffs applied, test specificity improved using a 2-antigen approach. Test performance was optimal using a 2-antigen assay with population-specific cutoffs (sensitivity, 73.9% 95% confidence interval CI, 51.6-89.8; specificity, 99.4% 95% CI, 97.7-99.9). We have addressed the problem of SARS-CoV-2 seroassay performance in Africa by using a 2-antigen assay with cutoffs defined by performance in the target population. Manning J, Zaidi I, Lon C, Rosas LA, Park JK, Ponce A, Bohl J, Chea S, Karkanitsa M, Sreng S, Rekol H, Chour CM, Esposito D, Taubenberger JK, Memoli MJ, Sadtler K, Duffy PE, Oliveira F. Pre-pandemic SARS-CoV-2 serological reactivity in rural malaria-experienced Cambodians. 2022. Emerging Infectious Diseases. Feb 1. Greater Mekong inhabitants are exposed to pathogens, zoonotic and otherwise, that may influence SARS-CoV-2 seroreactivity. A pre-pandemic (2005 to 2011) serosurvey of from 528 malaria-experienced Cambodians demonstrated higher-than-expected (up to 13.8 %) positivity of non-neutralizing IgG to SARS-CoV-2 spike and RBD antigens. These findings have implications for interpreting large-scale serosurveys. Scaria PV, Rowe CG, Chen BB, Dickey TH, Renn JP, Lambert LE, Barnafo EK, Rausch KM, Tolia NH, Duffy PE. Protein-protein conjugation enhances the immunogenicity of SARS-CoV-2 receptor-binding domain (RBD) vaccines. iScience. 2022 Aug 19;25(8):104739. doi: 10.1016/j.isci.2022.104739. Epub 2022 Jul 9. PMID: 35846379; PMCID: PMC9270177. Receptor binding domain of the SARS-CoV-2 Spike protein was conjugated to a carrier protein. This conjugate has demonstrated significantly higher immunogenicity compared to unconjugated antigen and the immune sera showed high levels of virus neutralizing functional activity against different variants of the SARS-CoV-2 virus. Further studies of this conjugate in non-human primate are ongoing. We also have initiated plan to develop Omicron specific vaccine candidate using this vaccine technology.

2020年7月，我们在马里现有的临床试验站点开始了一项社区Covid-19-19-19。这项研究是与马里卫生部合作的公共卫生监视活动，以描述城市和农村人口中Covid-19的血清流行病学。使用从参与者那里收集的人口统计和临床信息，我们将描述年龄分层的血清阳性和无症状/症状症状病例的分数，以帮助了解SARS-COV-2对社区的渗透。已经添加了其他探索性目标，以了解病毒运输，局部循环的变体和改善研究地点的直接病毒检测，以帮助提高当地公共卫生监测的能力和可能的未来临床试验。另外，我们利用内部疫苗平台开发了Covid-19候选疫苗，这些疫苗可能适合在马里等低/中收入国家使用。 从今年的出版物中，我们报告了2022财年的以下进展： Woodford J，Sagara I，Diawara H，Assadou M，Katile A，Attaher O，Issiaka D，Santara G Soumbounou I，Traore S，Traore M，Dicko O，Niambele S，Niambele S，Mahamar A，Mahamar A，Kamate B，Kamate B，Kamate B，Haidara B，Haidara B，Haidara k，Sissoko K，Sissoko K，Sissoko K，Sissoko K，Sissoko K，Sankare S，Zaid imakare S，Zaid Zaid Zeegime j， Dicko A，Duffy PE。最近的疟疾并未实质上影响疟疾较高和COVID-19在西非马里传播的社区的COVID-19抗体反应或症状疾病率。 2022。免疫学领域。 8月3日。 疟疾已被认为是可能降低撒哈拉以南非洲大流行的严重程度的因素。为了评估最近疟疾对Covid-19的影响，我们评估了参与纵向队列COHORT COVID-19SSEROSURVEEY的一个子组，这些人在2020年在Mali的传播季节期间也接受了强烈的疟疾监测，这些疟疾也正在接受密集的疟疾监测。这些社区在2020年和2021年期间主要出现了主要无症状或轻度共同的发病率。在1314个人中，有711个患有间交流寄生虫； 442是临床疟疾的症状，有269例无症状寄生虫病。间流寄生虫血症与新的COVID-19血清转化无关（29.7％（211/711）vs. 30.0％（181/603），P = 0.9038），或在疟疾传输季节期间报告的症状血清转化率。在随后的干旱季节，先前的寄生虫血症与新的covid-19-19（22.0％（133/605）vs.22.1％（108/488），p> 0.9999），具有症状性血清转化，具有从血清阳性到呼吸症之前的反向（6.2％）（36.2％）（36.2％）寄生虫：30.1％（37/119），p = 0.3842）。在排除无症状寄生虫血症的参与者之后，与在监测期内没有寄生虫血症的参与者相比，临床疟疾也与COVID-19-19-190-19血清表现或有症状的血清转化无关。在患有强烈季节性疟疾的社区，无症状或轻度Covid-19的发病率很高，我们没有证明最近疟疾与随后对Covid-19的反应之间的关系。终生暴露而不是最近的感染，可能是疟疾对COVID-19的严重程度的任何影响。 Woodford J，Sagara I，Kwan JL，Zaidi I，Dicko A，Duffy PE。评估和最小化疟疾对SARS-COV-2血清诊断的影响。 2021。热带疾病的边界。 12月13日。 疟疾可能会影响SARS-COV-2血清表现的可靠性，并限制对疟疾流行区域中SARS-COV-2流行病学的了解。我们介绍了在季节性疟疾影响的马里群落中进行SARS-COV-2血清监视的经验，并讨论了有关疟疾对SARS-COV-2血清诊断性能的影响的相关文献，包括最小化疟疾相关测定的效果的方法。 Woodford J，Sagara I，Dicko A，Zeguime A，Doucoure M，Kwan J，Zaidi I，Doritchamou Jya，Snow-Smith M，Alani N，Renn JP，Kosik I，Kosik I，Holly J，Yewdell J，Yewdell J，Esposito D，Sadtler K，Duffy Pe。 MALI背景反应高的人群中的SARS-COV-2血清表现和优化。 2021年。传染病杂志。 10月6日。 假阳性可能会阻碍严重的急性呼吸综合症冠状病毒2（SARS-COV-2）在撒哈拉以南非洲的血清学检查。从2020年之前收集的312个马里样品中，我们通过酶联免疫吸收测定法（ELISA）测量了对常见测试的SARS-COV-2抗原和其他4种BETACORONAVIRUS的抗体。在样品的一部分中，我们通过悬浮珠阵列和SARS-COV-2假病毒中和测定法评估了对恶性疟原虫抗原的抗体。然后，我们使用Malian阳性对照样品在美国开发的SARS-COV-2尖峰蛋白和受体结合结构域评估了ELISA的性能。为了优化测试性能，我们使用现有的测定截止和特定于人群的截止方法比较了单抗原方法。对SARS-COV-2抗原的背景反应性在马里亚式样品中很常见。 SARS-COV-2反应性在社区之间有所不同，随着年龄的增长而增加，并且与其他Betacoronavirus和Falciparum P. p. p. versibies相关。没有流行前样品表现出功能活性。无论应用临界值如何，都使用2-抗原方法提高了测试特异性。测试性能是使用具有特定人群特异性截止的2个抗原测定法（灵敏度为73.9％95％置信区间CI，51.6-89.8;特异性，99.4％95％CI，97.7-99.9）。我们已经通过使用2个抗原测定法和目标人群定义的2个抗原测定法，解决了非洲SARS-COV-2 Seroassay性能的问题。 Manning J, Zaidi I, Lon C, Rosas LA, Park JK, Ponce A, Bohl J, Chea S, Karkanitsa M, Sreng S, Rekol H, Chour CM, Esposito D, Taubenberger JK, Memoli MJ, Sadtler K, Duffy PE, Oliveira F. Pre-pandemic SARS-CoV-2 serological reactivity in rural malaria-experienced柬埔寨人。 2022年。新兴的传染病。 2月1日。 大湄公河居民暴露于死亡人畜，其他情况下，可能会影响SARS-COV-2的血清反应性。从528种疟疾经验的柬埔寨人对528个疟疾的血清群体表现出比非中性IgG对SARS-COV-COV-2尖峰和RBD抗原的阳性高于预期的（高达13.8％）的阳性。这些发现对解释大规模的血清外生有影响。 Scaria PV，Rowe CG，Chen BB，Dickey TH，Renn JP，Lambert LE，Barnafo EK，Rausch KM，Tolia NH，Duffy PE。蛋白质蛋白结合增强了SARS-COV-2受体结合结构域（RBD）疫苗的免疫原性。 Iscience。 2022年8月19日； 25（8）：104739。 doi：10.1016/j.isci.2022.104739。 EPUB 2022 7月9日。PMID：35846379; PMCID：PMC9270177。 SARS-COV-2尖峰蛋白的受体结合结构域与载体蛋白结合。与未结合的抗原相比，这种结合物的免疫原性显着更高，免疫血清表现出高水平的病毒中和对SARS-COV-2病毒不同变异的功能活性。对非人类灵长类动物的这种共轭的进一步研究正在进行中。我们还启动了使用这种疫苗技术开发特定于Omicron特定疫苗的计划。