A Phase 1 randomized trial of homologous and heterologous filovirus vaccines with a late booster dose.

Filoviruses, including Ebola, Marburg, Sudan, and Taï Forest viruses, are zoonotic pathogens that can cause severe viral hemorrhagic fever and death. Developing vaccines that provide durable, broad immunity against multiple filoviruses is a high global health priority. In this Phase 1 trial, we enrolled 60 healthy U.

Evaluation of Immunoglobulin A Enzyme Immunoassays to Detect Primary Respiratory Syncytial Virus Infection in Infants and Young Children.

Background: Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infections in children <2 years of age. Prior infection in a child is usually determined by RSV antibodies; however, in young children, persisting maternal immunoglobulin G antibodies can incorrectly indicate past RSV infection. We developed and evaluated 4 immunoglobulin A (IgA) antibody enzyme immunoassays (EIAs) with the RSV F, subgroup G (Ga or Gb proteins) or RSV lysate antigens to distinguish infection induced from persisting maternal RSV antibodies.

Altered Spike Immunoglobulin G Fc N-Linked Glycans Are Associated With Hyperinflammatory State in Adult Coronavirus Disease 2019 and Multisystem Inflammatory Syndrome in Children.

Background: Severe coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome (MIS-C) are characterized by excessive inflammatory cytokines/chemokines. In adults, disease severity is associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunoglobulin G (IgG) Fc afucosylation, which induces proinflammatory cytokine secretion from innate immune cells. This study aimed to define spike IgG Fc glycosylation following SARS-CoV-2 infection in adults and children and following SARS-CoV-2 vaccination in adults and the relationships between glycan modifications and cytokines/chemokines.

Plasma cell-free RNA signatures of inflammatory syndromes in children.

Inflammatory syndromes, including those caused by infection, are a major cause of hospital admissions among children and are often misdiagnosed because of a lack of advanced molecular diagnostic tools. In this study, we explored the utility of circulating cell-free RNA (cfRNA) in plasma as an analyte for the differential diagnosis and characterization of pediatric inflammatory syndromes. We profiled cfRNA in 370 plasma samples from pediatric patients with a range of inflammatory conditions, including Kawasaki disease (KD), multisystem inflammatory syndrome in children (MIS-C), viral infections, and bacterial infections.

Clinical Features and Outcomes of Pediatric and Adult Patients Hospitalized for Coronavirus Disease 2019: A Comparison Across Age Strata.

Background: Coronavirus disease 2019 (COVID-19) continues to cause hospitalizations and severe disease in children and adults.

Methods: This study compared the risk factors, symptoms, and outcomes of children and adults hospitalized for COVID-19 from March 2020 to May 2023 across age strata at 5 US sites participating in the Predicting Viral-Associated Inflammatory Disease Severity in Children with Laboratory Diagnostics and Artificial Intelligence consortium. Eligible patients had an upper respiratory swab that tested positive for severe acute respiratory syndrome coronavirus 2 by nucleic acid amplification.

Long-term Health Outcomes After Hospital Discharge Among Children Hospitalized for MIS-C or COVID-19, September 29, 2021, to June 21, 2022.

Background: The long-term effects of children hospitalized with multisystem inflammatory syndrome in children (MIS-C) or acute COVID-19 are not well known. Our objective was to determine long-term outcomes.

Methods: Children hospitalized with MIS-C or COVID-19 at 3 US hospitals from March 2020, through February 2021 were followed to assess health through 2 years post-hospitalization using medical records and patient surveys.

Safety and Immunogenicity of an mRNA-1273 Booster in Children.

Background: A 2-dose mRNA-1273 primary series in children aged 6 months-5 years (25 µg) and 6-11 years (50 µg) had an acceptable safety profile and was immunogenic in the phase 2/3 KidCOVE study. We present data from KidCOVE participants who received an mRNA-1273 booster dose.

Methods: An mRNA-1273 booster dose (10 µg for children aged 6 months-5 years; 25 µg for children aged 6-11 years; age groups based on participant age at enrollment) was administered ≥6 months after primary series completion.

Altered spike IgG Fc N-linked glycans are associated with hyperinflammatory state in adult COVID and Multisystem Inflammatory Syndrome in Children.

Background: Severe COVID and multisystem inflammatory syndrome (MIS-C) are characterized by excessive inflammatory cytokines/chemokines. In adults, disease severity is associated with SARS-CoV-2-specific IgG Fc afucosylation, which induces pro-inflammatory cytokine secretion from innate immune cells. This study aimed to define spike IgG Fc glycosylation following SARS-CoV-2 infection in adults and children and following SARS-CoV-2 vaccination in adults and the relationships between glycan modifications and cytokine/chemokine levels.

Relative Contribution of Diagnostic Testing to the Diagnosis of Respiratory Syncytial Virus in Hospitalized Adults in the United States.

Background: Respiratory syncytial virus (RSV) is a leading cause of acute respiratory illness (ARI) in older adults. Optimizing diagnosis could improve understanding of RSV burden.

Methods: We enrolled adults ≥50 years of age hospitalized with ARI and adults of any age hospitalized with congestive heart failure or chronic obstructive pulmonary disease exacerbations at 2 hospitals during 2 respiratory seasons (2018-2020).

Effectiveness of BNT162b2 Vaccine for Preventing COVID-19-Related Hospitalizations: A Test-Negative Case-Control Study.

It is important to understand real-world BNT162b2 COVID-19 vaccine effectiveness (VE), especially among racial and ethnic minority groups. We performed a test-negative case-control study to measure BNT162b2 COVID-19 VE in the prevention of COVID-19-associated acute respiratory illness (ARI) hospitalizations at two Atlanta hospitals from May 2021-January 2023 and adjusted for potential confounders by multivariate analysis. Among 5139 eligible adults with ARI, 2763 (53.

Experimental trials of predicted CD4 and CD8 T-cell epitopes of respiratory syncytial virus.

Background: Respiratory syncytial virus (RSV) is the most common cause of viral lower respiratory tract infections (LRTIs) in young children around the world and an important cause of LRTI in the elderly. The available treatments and FDA-approved vaccines for RSV only lessen the severity of the infection and are recommended for infants and elderly people.

Methods: We focused on developing a broad-spectrum vaccine that activates the immune system to directly combat RSV.

A Phase 2 Clinical Trial to Evaluate the Safety, Reactogenicity, and Immunogenicity of Different Prime-Boost Vaccination Schedules of 2013 and 2017 A(H7N9) Inactivated Influenza Virus Vaccines Administered With and Without AS03 Adjuvant in Healthy US Adults.

Introduction: A surge of human influenza A(H7N9) cases began in 2016 in China from an antigenically distinct lineage. Data are needed about the safety and immunogenicity of 2013 and 2017 A(H7N9) inactivated influenza vaccines (IIVs) and the effects of AS03 adjuvant, prime-boost interval, and priming effects of 2013 and 2017 A(H7N9) IIVs.

Methods: Healthy adults (n = 180), ages 19-50 years, were enrolled into this partially blinded, randomized, multicenter phase 2 clinical trial.

A Phase 1, Double-Blinded, Placebo-Controlled Clinical Trial to Evaluate the Safety and Immunogenicity of HEV-239 (Hecolin) Vaccine in Healthy US Adults.

Background: Establishing the safety and immunogenicity of a hepatitis E virus vaccine in multiple populations could facilitate broader access and prevent maternal and infant mortality.

Methods: We conducted a phase 1, randomized, double-blinded, placebo-controlled (4:1 vaccine to placebo) trial of 30 µg HEV-239 (Hecolin, Xiamen Innovax Biotech Company Limited, China) administered intramuscularly in healthy US adults aged 18-45 years. Participants were vaccinated on days 1, 29, and 180.

Development and comparison of immunologic assays to detect primary RSV infections in infants.

Effective respiratory syncytial virus (RSV) vaccines have been developed and licensed for elderly adults and pregnant women but not yet for infants and young children. The RSV immune state of the young child, i.e.

Immunogenicity and safety of varying dosages of a fifth-wave influenza A/H7N9 inactivated vaccine given with and without AS03 adjuvant in healthy adults.

Background: Human infections with the avian influenza A(H7N9) virus were first reported in China in 2013 and continued to occur in annual waves. In the 2016/2017 fifth wave, Yangtze River Delta (YRD) lineage viruses, which differed antigenically from those of earlier waves, predominated.

Methods: In this phase 2 double-blinded trial we randomized 720 adults ≥ 19 years of age to receive two injections of a YRD lineage inactivated A/Hong Kong/125/2017 fifth-wave H7N9 vaccine, given 21 days apart, at doses of 3.

SARS-CoV-2 Antibody Profiles in Maternal Serum and Breast Milk Following mRNA COVID-19 Vaccination: A Longitudinal Prospective Observational Cohort Study.

COVID-19 vaccination during pregnancy protects infants against symptomatic COVID-19. Vaccination of lactating mothers may offer additional protection, but our understanding of immune responses in breast milk is limited. We, therefore, performed a single-center prospective cohort study of lactating mothers who received a COVID-19 mRNA primary vaccine series to evaluate the durability, breadth, and neutralizing capacity of the antibody responses in breast milk.

Influenza Vaccine Effectiveness Pre-pandemic Among Adults Hospitalized With Congestive Heart Failure or Chronic Obstructive Pulmonary Disease and Older Adults.

Background: Data are limited on influenza vaccine effectiveness (VE) in the prevention of influenza-related hospitalizations in older adults and those with underlying high-risk comorbidities.

Methods: We conducted a prospective, test-negative, case-control study at 2 US hospitals from October 2018-March 2020 among adults aged ≥50 years hospitalized with acute respiratory illnesses (ARIs) and adults ≥18 years admitted with congestive heart failure (CHF) or chronic obstructive pulmonary disease (COPD) exacerbations. Adults were eligible if they resided in 1 of 8 counties in metropolitan Atlanta, Georgia.

Immunogenicity of NVX-CoV2373 heterologous boost against SARS-CoV-2 variants.

As part of a multicenter study evaluating homologous and heterologous COVID-19 booster vaccines, we assessed the magnitude, breadth, and short-term durability of binding and pseudovirus-neutralizing antibody (PsVNA) responses following a single booster dose of NVX-CoV2373 in adults primed with either Ad26.COV2.S, mRNA-1273, or BNT162b2 vaccines.

Respiratory Coinfections in Children With SARS-CoV-2.

Background: As the transmission of endemic respiratory pathogens returns to prepandemic levels, understanding the epidemiology of respiratory coinfections in children with SARS-CoV-2 is of increasing importance.

Methods: We performed a retrospective analysis of all pediatric patients 0-21 years of age who had a multiplexed BioFire Respiratory Panel 2.1 test performed at Children's Healthcare of Atlanta, Georgia, from January 1 to December 31, 2021.

Longitudinal Neutralizing and Functional Antibody Responses to Severe Acute Respiratory Syndrome Coronavirus 2 Variants Following Messenger RNA Coronavirus Disease 2019 Vaccination.

In this longitudinal prospective cohort of healthy adults in the United States, we found that coronavirus disease 2019 messenger RNA primary series and booster vaccinations elicited high titers of broadly cross-reactive neutralizing and antibody-dependent cell-mediated cytotoxicity antibodies, which gradually waned over 6 months, particularly against severe acute respiratory syndrome coronavirus 2 variants. These data support the indication for a subsequent booster vaccination.