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The Advisory Committee on Immunization Practices (ACIP), a group of medical and public health experts who provides expert advice to the Centers for Disease Control and Prevention, normally meets three times per year to develop U.S. vaccine recommendations. The ACIP met on February 22–24, 2023, to discuss mpox vaccine, influenza vaccines, pneumococcus vaccines, meningococci vaccines, polio vaccines, respiratory syncytial virus (RSV) vaccine, chikungunya vaccines, dengue vaccines, and COVID-19 vaccines.

Background Breakthrough infections post-COVID-19 vaccination increase with waning immunity and typically produce milder disease than infections in unvaccinated individuals. We investigated immuno-virologic responses and COVID-19 symptom burden upon breakthrough infection in participants from a Phase 3 study of 2-dose primary series AZD1222 vaccination (NCT04516746) to explore disease attenuation. Methods Study participants who experienced protocol-defined COVID-19 symptoms initiated a series of illness visits over 28 days with collection of sera, nasopharyngeal (NP) swabs and saliva samples (SS), and documentation of symptoms (data-cut off: July 30, 2021). For baseline-seronegative participants with PCR-confirmed SARS-CoV-2 infection ≥15 days after dose 2 of AZD1222 or placebo we assessed: anti-SARS-CoV-2 spike (S), nucleocapsid (N) and neutralizing antibody (Ab) titers by multiplex immunoassay and SARS-CoV-2 pseudovirus assay in sera; viral load by quantitative RT-PCR in NP swabs; and viral shedding by qualitative and quantitative RT-PCR in SS. Data were stratified by age and SARS-CoV-2 variant, and time since primary series dose 2. Results Illness Day 1 (ILL-D1) S Ab GMTs in AZD1222 vaccinees were similar to peak GMTs seen 14 days after dose 2 of AZD1222 and were higher vs placebo at all timepoints. The magnitude of S Ab response differed by age: median GMTs were lower at ILL-D1 and higher at ILL-D14 in vaccinees aged ≥65 vs 18–64 years (Fig.1). ILL-D1 overall, SARS-CoV-2 ancestral, alpha, and epsilon variant viral load titers in NP swabs were lower in vaccinees vs placebo (Fig 2). Mean viral load in NP swabs and viral shedding titers in SS were lower in vaccinees vs placebo at all timepoints. Vaccinees reported fewer COVID-19 symptoms than placebo participants, and experienced shorter symptom duration, particularly for fatigue and difficulty breathing. Figure 1. SARS-CoV-2 spike IgG antibody titers upon SARS-CoV-2 infection by participant age in AZD1222 vaccinees and placebo recipients during illness visits Figure 2. Quantification of viral load (nasopharyngeal swabs quantitative viral titer) by SARS-CoV-2 variant at Illness Visit Day 1 Conclusion Improved S Ab responses, lower viral loads, and reduced symptom burden upon breakthrough infection in vaccinees vs placebo recipients, suggest that robust recall responses to AZD1222 vaccination may attenuate COVID-19 disease severity and duration. These findings alongside data on cellular immune responses to breakthrough infection will inform understanding of protective immunity to SARS-CoV-2 infection. Disclosures Magdalena E. Sobieszczyk, MD, MPH, Bill and Melinda Gates Foundation: Grant/Research Support|Gilead Sciences: Grant/Research Support|Janssen Global Services, LLC: Grant/Research Support|Merck: Grant/Research Support|National Institute of Allergy and Infectious Diseases (NIAID): Grant/Research Support|National Institutes of Health (NIH): Grant/Research Support|Sanofi Pasteur Inc.: Grant/Research Support Ann R. Falsey, MD, BioFire Diagnostics: Grant/Research Support|Janssen: Grant/Research Support|Merck, Sharp and Dohme: Grant/Research Support|Novavax: Advisor/Consultant|Pfizer: Grant/Research Support Anne F. Luetkemeyer, MD, AstraZeneca: Grant/Research Support|Gilead Sciences: Grant/Research Support Grant C. Paulsen, MD, AstraZeneca: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support Sharon A. Riddler, MD, National Institute of Allergy and Infectious Diseases (NIAID): Grant/Research Support|National Institutes of Health (NIH): Grant/Research Support|Novimmune: Advisor/Consultant Merlin L. Robb, MD, Walter Reed Army Institute of Research: Advisor/Consultant Charlotte-Paige M. Rolle, MD, MPH, Gilead Sciences: Board Member|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria|Janssen: Board Member|ViiV Healthcare: Board Member|ViiV Healthcare: Grant/Research Support|ViiV Healthcare: Honoraria|Vindico CME: Honoraria Beverly E. Sha, MD, Gilead Sciences: Grant/Research Support|MATEC: Honoraria|University of Chicago: Grant/Research Support|US Government: Grant/Research Support Bahar Ahani, BSC, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Anastasia A. Aksyuk, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Himanshu Bansal, MS, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Justin A. Green, MD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Brett Jepson, MS, AstraZeneca: Contractor via Cytel Jill Maaske, MD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Kathryn Shoemaker, MS, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Stephanie Sproule, MMath, AstraZeneca: Contractor via Joule/System One Ann Marie Stanley, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Deidre Wilkins, BSC, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Tonya L. Villafana, PhD, MPH, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Elizabeth J. Kelly, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds.

Background Effective therapeutic agents for the treatment of COVID-19 have been investigated since the onset of the pandemic. Monoclonal antibodies targeting the spike protein of SARS-CoV-2 have been developed for treatment of mild or moderate COVID disease in high-risk populations. Despite widespread use in the adult population, data are limited on the safety and efficacy of monoclonal antibody infusions in the adolescent and young adult population. Methods Patients who received bamlanivimab, bamlanivimab-etesevimab, casirivimab-imdevimab, or sotrovimab for treatment of mild COVID disease at Cincinnati Children’s Hospital Medical Center from 5/1/2020 through 3/1/2022 were identified retrospectively. In accordance with the FDA EUA, patients were eligible for monoclonal antibody administration if they were ≥12 years of age, weighed ≥40kg, and were at high risk of progressing to severe disease or hospitalization. Results Ninety-four patients received monoclonal antibody therapy, of which 14 (13.5%) received either bamlanivimab or bamlanivimab-etesevimab, 54 (51.9%) received casirivimab-imdevimab, and 26 (25%) received sotrovimab. Ten patients (10.6%) experienced one or more adverse events. Of those, 2 (14.3%) received either bamlanivimab or bamlanivimab-etesivimab, 7 (12.9%) received casirivimab-imdevimab, and 1 (3.8%) received sotrovimab. Most common symptoms include rash, nausea, and throat irritation (table R1), the majority (90%) of which were mild, either self-resolving with infusion cessation (60%) or persistent but requiring no medical intervention (30%) (table R2). Of the patients who experienced adverse events, only 1 (10%) received medical intervention - epinephrine. No life-threatening events or deaths occurred. Within 90 days of receiving a monoclonal antibody, 15 patients (15.9%) required additional medical care for ongoing COVID symptoms (table R3). Eight (53.3%) of these were either hospitalized or received escalation of care while already in the hospital. Table R1. Infusion-related adverse events. Of note, several patients had more than one symptom. Table R2. Classification of adverse events by grade and monoclonal antibody. Grade I events are defined as mild and generally not bothersome. Grade II events are defined as moderate: bothersome, but not dangerous. Grade III events are defined as medically significant, but not immediately life-threatening, and often require medical intervention. Table R3. Patients who required additional medical care for ongoing COVID-19 symptoms within 90 days of receiving a monoclonal antibody. Conclusion Overall, monoclonal antibodies are safe, largely well-tolerated COVID-19 therapies in high-risk adolescent and young adult populations. Disclosures Grant Schulert, MD, PhD, Novartis: Advisor/Consultant Paul Spearman, MD, CyanVac: Grant/Research Support|Meissa Vaccines: Grant/Research Support Grant C. Paulsen, MD, AstraZeneca: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support Lara A. Danziger-Isakov, MD, Ansun BioPharma: Contracted clinical research|Astellas: Contracted clinical research|GSK: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Contracted clinical research|Pfizer: Contracted clinical research|Takeda: Grant/Research Support|Takeda: Contracted clinical research|Viracor: Grant/Research Support.

Background Safe, effective vaccines against coronavirus disease 2019 (Covid-19) are urgently needed in children younger than 12 years of age. Methods A phase 1, dose-finding study and an ongoing phase 2-3 randomized trial are being conducted to investigate the safety, immunogenicity, and efficacy of two doses of the BNT162b2 vaccine administered 21 days apart in children 6 months to 11 years of age. We present results for 5-to-11-year-old children. In the phase 2-3 trial, participants were randomly assigned in a 2:1 ratio to receive two doses of either the BNT162b2 vaccine at the dose level identified during the open-label phase 1 study or placebo. Immune responses 1 month after the second dose of BNT162b2 were immunologically bridged to those in 16-to-25-year-olds from the pivotal trial of two 30-μg doses of BNT162b2. Vaccine efficacy against Covid-19 at 7 days or more after the second dose was assessed. Results During the phase 1 study, a total of 48 children 5 to 11 years of age received 10 μg, 20 μg, or 30 μg of the BNT162b2 vaccine (16 children at each dose level). On the basis of reactogenicity and immunogenicity, a dose level of 10 μg was selected for further study. In the phase 2-3 trial, a total of 2268 children were randomly assigned to receive the BNT162b2 vaccine (1517 children) or placebo (751 children). At data cutoff, the median follow-up was 2.3 months. In the 5-to-11-year-olds, as in other age groups, the BNT162b2 vaccine had a favorable safety profile. No vaccine-related serious adverse events were noted. One month after the second dose, the geometric mean ratio of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing titers in 5-to-11-year-olds to those in 16-to-25-year-olds was 1.04 (95% confidence interval [CI], 0.93 to 1.18), a ratio meeting the prespecified immunogenicity success criterion (lower bound of two-sided 95% CI, >0.67; geometric mean ratio point estimate, ≥0.8). Covid-19 with onset 7 days or more after the second dose was reported in three recipients of the BNT162b2 vaccine and in 16 placebo recipients (vaccine efficacy, 90.7%; 95% CI, 67.7 to 98.3). Conclusions A Covid-19 vaccination regimen consisting of two 10-μg doses of BNT162b2 administered 21 days apart was found to be safe, immunogenic, and efficacious in children 5 to 11 years of age. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04816643.).