An introduction of the Accelerated Development of VAccine beNefit-risk Collaboration in Europe (ADVANCE) Project

The vaccine benefit-risk assessment entails comprehensive and systematic evaluation of the major benefits and risks of vaccine based on information after a marketing authorization. In 2009, the influenza A (H1N1) pandemic led to the licensing of new H1N1 vaccines in many countries including Europe. The post-marketing evaluation and monitoring of H1N1 vaccines was carried out based on a project previously conducted in Europe. In 2013, the Accelerated Development of VAccine beNefit-risk Collaboration in Europe (ADVANCE) project was launched with the support of Innovative Medicines Initiative (IMI) to address the limitations reported in the previous project. ADVANCE consisted of seven Work Packages (WPs), each indicating the vaccine benefitrisk monitoring readiness across four areas: Governance, Data source, Methods, and Study. First, a model for vaccine surveillance and governance with various functions such as decision making, quality management, execution, and financial administration was established. Also, the project developed a tool to identify, collect, and link the data sources available for vaccine surveillance. In addition, various methodologies were reviewed to assess the infectious disease burden, vaccine coverage, and benefit-risk based on linked data sources in Europe. Guidelines were proposed for real-world vaccine surveillance studies. Accordingly, a variety of tools and programs were developed, including a code of conduct related to the benefit-risk assessment of vaccines, ADVANCE International Research Readiness (AIRR), CodeMapper, and VaccO. Since the end of the ADVANCE project in 2019, the Vaccine Monitoring Collaboration for Europe (VAC4EU) has been conducting effective and sustainable vaccine benefit-risk monitoring programs based on the vision and ideology of ADVANCE. This study explains the contents and findings of ADVANCE with emphasis on WPs and proposes directions for establishing a vaccine benefit-risk assessment system in Korea.

Detection of Enterotoxigenic Escherichia coli in Rotavirus-Infected Ghanaian Children Diagnosed with Acute Gastroenteritis

Diarrhea is a notable global health problem in several developing countries, especially in children. Prior to the introduction of the rotavirus vaccination program in Ghana, a surveillance study was conducted to investigate the prevalence of the disease caused by rotavirus in children. In this report, we re-used archival stool samples from the pre-vaccine surveillance study to provide information on prevalence of enterotoxigenic Escherichia coli in Ghanaian children. Re-analysis of the stool samples revealed co-infection of enterotoxigenic E. coli and rotavirus in 2% of the children whose samples were selected for this study. As Ghana is approaching 10 years post-implementation of the rotavirus vaccination program, the preliminary data presented in this report are a vital reference for subsequent studies aimed at ascertaining the effect of the vaccine on both rotavirus and enterotoxigenic E. coli.

154. Circulation of Rhinovirus/Enterovirus Respiratory Infections in Children During 2020-21 in the United States

Background Sharp declines in influenza and respiratory syncytial virus (RSV) circulation across the U.S. have been described during the pandemic in temporal association with community mitigation for control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to determine relative frequencies of rhinovirus/enterovirus (RV/EV) and other respiratory viruses in children presenting to emergency departments or hospitalized with acute respiratory illness (ARI) prior to and during the COVID-19 pandemic. Methods We conducted a multi-center active prospective ARI surveillance study in children as part of the New Vaccine Surveillance Network (NVSN) from December 2016 through January 2021. Molecular testing for RV/EV, RSV, influenza, and other respiratory viruses [i.e., human metapneumovirus, parainfluenza virus (Types 1-4), and adenovirus] were performed on specimens collected from children enrolled children. Cumulative percent positivity of each virus type during March 2020–January 2021 was compared from March-January in the prior seasons (2017-2018, 2018-2019, 2019-2020) using Pearson’s chi-squared. Data are provisional. Results Among 69,403 eligible children, 37,676 (54%) were enrolled and tested for respiratory viruses. The number of both eligible and enrolled children declined in early 2020 (Figure 1), but 4,691 children (52% of eligible) were enrolled and tested during March 2020-January 2021. From March 2020-January 2021, the overall percentage of enrolled children with respiratory testing who had detectable RV/EV was similar compared to the same time period in 2017-2018 and 2019-2020 (Figure 1, Table 1). In contrast, the percent positivity of RSV, influenza, and other respiratory viruses combined declined compared to prior years, (p< 0.001, Figure 1, Table 1). Figure 1. Percentage of Viral Detection Among Enrolled Children Who Received Respiratory Testing, New Vaccine Surveillance Network (NVSN), United States, December 2016 – January 2021 Table 1. Percent of Respiratory Viruses Circulating in March 2020– January 2021, compared to March-January in Prior Years, New Vaccine Surveillance Network (NVSN), United States, March 2017 – January 2021 Conclusion During 2020, RV/EV continued to circulate among children receiving care for ARI despite abrupt declines in other respiratory viruses within this population. These findings warrant further studies to understand virologic, behavioral, biological, and/or environmental factors associated with this continued RV/EV circulation. Disclosures Jennifer E. Schuster, MD, Merck, Sharpe, and Dohme (Individual(s) Involved: Self): Grant/Research Support Marian G. Michaels, MD, MPH, Viracor (Grant/Research Support, performs assay for research study no financial support) John V. Williams, MD, GlaxoSmithKline (Advisor or Review Panel member, Independent Data Monitoring Committee)Quidel (Advisor or Review Panel member, Scientific Advisory Board) Elizabeth P. Schlaudecker, MD, MPH, Pfizer (Grant/Research Support)Sanofi Pasteur (Advisor or Review Panel member) Christopher J. Harrison, MD, GSK (Grant/Research Support)Merck (Grant/Research Support)Pfizer (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) Janet A. Englund, MD, AstraZeneca (Consultant, Grant/Research Support)GlaxoSmithKline (Research Grant or Support)Meissa Vaccines (Consultant)Pfizer (Research Grant or Support)Sanofi Pasteur (Consultant)Teva Pharmaceuticals (Consultant) Claire Midgley, PhD, Nothing to disclose Natasha B. Halasa, MD, MPH, Genentech (Other Financial or Material Support, I receive an honorarium for lectures - it’s a education grant, supported by genetech)Quidel (Grant/Research Support, Other Financial or Material Support, Donation of supplies/kits)Sanofi (Grant/Research Support, Other Financial or Material Support, HAI/NAI testing) Natasha B. Halasa, MD, MPH, Genentech (Individual(s) Involved: Self): I receive an honorarium for lectures - it’s a education grant, supported by genetech, Other Financial or Material Support, Other Financial or Material Support; Sanofi (Individual(s) Involved: Self): Grant/Research Support, Research Grant or Support

Effect of Vaccination on Preventing Influenza-Associated Hospitalizations Among Children During a Severe Season Associated with B/Victoria Viruses, 2019-2020

Background The 2019-2020 influenza season was characterized by early onset with B/Victoria followed by A(H1N1)pdm09 viruses. Emergence of new B/Victoria viruses raised concerns about possible vaccine mismatch. We estimated vaccine effectiveness (VE) against influenza-associated hospitalizations and emergency department (ED) visits among U.S. children. Methods We assessed VE among children 6 months–17 years with acute respiratory illness and ≥10 days of symptoms enrolled at 7 pediatric medical centers in the New Vaccine Surveillance Network. Combined mid-turbinate/throat swabs were tested for influenza virus using molecular assays. Vaccination history was collected from parental report, state immunization information systems, and/or provider records. We estimated VE from a test-negative design using logistic regression to compare odds of vaccination among children testing positive versus negative for influenza. Results Among 2029 inpatients, 335 (17%) were influenza positive: 37% with influenza B/Victoria alone and 44% with influenza A(H1N1)pdm09 alone.VE was 62% (95% confidence interval [CI], 52%–71%) for influenza-related hospitalization, 54% (95% CI, 33%–69%) for B/Victoria viruses and 64% (95% CI, 49%–75%) for A(H1N1)pdm09. Among 2102 ED patients, 671 (32%) were influenza positive: 47% with influenza B/Victoria alone and 42% with influenza A(H1N1)pdm09 alone. VE was 56% (95% CI, 46%–65%) for an influenza-related ED visit, 55% (95% CI, 40%–66%) for B/Victoria viruses and 53% (95% CI, 37%–65%) for A(H1N1)pdm09. Conclusions Influenza vaccination provided significant protection against laboratory-confirmed influenza-associated hospitalizations and ED visits associated with the two predominantly circulating influenza viruses among children, including against the emerging B/Victoria virus subclade.

An integrated in silico immuno-genetic analytical platform provides insights into COVID-19 serological and vaccine targets

During COVID-19, diagnostic serological tools and vaccines have been developed. To inform control activities in a post-vaccine surveillance setting, we have developed an online “immuno-analytics” resource that combines epitope, sequence, protein and SARS-CoV-2 mutation analysis. SARS-CoV-2 spike and nucleocapsid proteins are both vaccine and serological diagnostic targets. Using the tool, the nucleocapsid protein appears to be a sub-optimal target for use in serological platforms. Spike D614G (and nsp12 L314P) mutations were most frequent (> 86%), whilst spike A222V/L18F have recently increased. Also, Orf3a proteins may be a suitable target for serology. The tool can accessed from: http://genomics.lshtm.ac.uk/immuno (online); https://github.com/dan-ward-bio/COVID-immunoanalytics (source code).

Continued Evidence of the Impact of Rotavirus Vaccine in Children Less Than 3 Years of Age From the United States New Vaccine Surveillance Network: A Multisite Active Surveillance Program, 2006–2016

Background Since 2006, the New Vaccine Surveillance Network has conducted active, population-based surveillance for acute gastroenteritis (AGE) hospitalizations and emergency department (ED) visits in 3 United States counties. Trends in the epidemiology and disease burden of rotavirus hospitalizations and ED visits were examined from 2006 to 2016. Methods Children < 3 years of age hospitalized or visiting the ED with AGE were enrolled from January 2006 through June 2016. Bulk stool specimens were collected and tested for rotavirus. Rotavirus-associated hospitalization and ED visit rates were calculated annually with 2006–2007 defined as the prevaccine period and 2008–2016 as the postvaccine period. Rotavirus genotype trends were compared over time. Results Over 11 seasons, 6954 children with AGE were enrolled and submitted a stool specimen (2187 hospitalized and 4767 in the ED). Comparing pre- and postvaccine periods, the proportion of children with rotavirus dramatically declined for hospitalization (49% vs 10%) and ED visits (49% vs 8%). In the postvaccine era, a biennial pattern of rotavirus rates was observed, with a trend toward an older median age. G1P[8] (63%) was the predominant genotype in the prevaccine period with a significantly lower proportion (7%) in the postvaccine period (P < .001). G2P[4] remained stable (8% to 14%) in both periods, whereas G3P[8] and G12P[8] increased in proportion from pre- to postvaccine periods (1% to 25% and 17% to 40%), respectively. Conclusions The epidemiology and disease burden of rotavirus has been altered by rotavirus vaccination with a biennial disease pattern, sustained low rates of rotavirus in children < 3 years of age, and a shift in the residual genotypes from G1P[8] to other genotypes.