Nasopharyngeal carriage of pneumococcus in children in England up to 10 years after 13-valent pneumococcal conjugate vaccine introduction: persistence of serotypes 3 and 19A and emergence of 7C

Background: Monitoring changes in pharyngeal carriage of pneumococcus in children following 13-valent pneumococcal conjugate vaccine (PCV13) introduction in the United Kingdom in 2010 informs understanding of patterns of invasive pneumococcal disease (IPD) incidence. Methods: Nasopharyngeal swabs from healthy children vaccinated with PCV13 according to schedule (2, 4, and 12 months) were cultured and serotyped. Results for children aged 13–48 months were compared between 2014–2015 and 2017–2019 and with children aged 6–12 months (2017–2020). Blood was obtained from a subset of children for pneumococcal serotype-specific immunoglobulin G (IgG). Results: Total pneumococcal carriage at 13–48 months was 47.9% (473/988) in 2014–2015 and 51.8% (412/795) in 2017–2019 (P = .10); at age 6–12 months this value was 44.6% (274/615). In 2017–2019, 2.9% (95% confidence interval, 1.8%–4.3%) of children aged 13–48 months carried PCV13 serotypes (mainly 3 [1.5%] and 19A [0.8%]) and >20% carried the additional 20-valent PCV (PCV20) serotypes. Similar proportions of children had IgG ≥0.35 IU/mL for each serotype in 2014–2015 and 2017–2019. Serotype 7C carriage increased significantly (P < .01) between 2014–2015 and 2017–2019. Carriage of PCV20 serotypes 8 and 12F, both major causes of IPD, was rare. Conclusions: Introduction of PCV20, if licensed for children, could significantly change the composition of pneumococcal serotypes carried in the pharynx of UK children. Clinical Trials Registration: NCT03102840

A Randomized Trial Assessing the Immunogenicity and Reactogenicity of Two Hexavalent Infant Vaccines Concomitantly Administered With Group B Meningococcal Vaccine

BACKGROUND: Three hexavalent (DTaP-IPV-Hib-HepB) vaccines are licensed in Europe, only one of which (Vaxelis, Hex-V), uses a meningococcal outer membrane protein complex as a carrier protein for Hemophilus influenza type b (Hib), creating potential interactions with the meningococcal vaccine 4CMenB. METHODS: In this single-center open-label randomized trial, infants were randomized in a 1:1 ratio to receive Hex-V or an alternative hexavalent vaccine (Infanrix-Hexa, Hex-IH) at 2, 3, and 4 months with 4CMenB (2, 4, and 12 months) in the UK routine immunization schedule. The primary outcome was noninferiority of geometric mean concentrations (GMCs) of anti-PRP (Hib) IgG at 5 months of age. Secondary outcomes included safety, reactogenicity, and immunogenicity of other administered vaccines measured at 5 and 13 months of age. RESULTS: Of the 194 participants enrolled, 96 received Hex-V and 98 Hex-IH. Noninferiority of anti-PRP IgG GMCs at 5 months of age in participants receiving Hex-V was established; GMCs were 23-times higher following three doses of Hex-V than three doses of Hex-IH (geometric mean ratio (GMR) 23.25; one-sided 95% CI 16.21, -). 78/85 (92%) of Hex-V recipients and 43/87 (49%) of Hex-IH recipients had anti-PRP antibodies ≥1.0 µg/mL. At 5 months of age serum, bactericidal activity titers against MenB strain 5/99 were higher following Hex-V than Hex-IH (GMR 1.56; 95% CI, 1.13-2.14). The reactogenicity profile was similar in both groups. CONCLUSIONS: These data support flexibility in the use of either Hex-IH or Hex-V in infant immunization schedules containing 4CMenB, with the possibility that Hex-V may enhance protection against Hib

Simultaneous viral whole-genome sequencing and differential expression profiling in respiratory syncytial virus infection of infants

Targeted metagenomics using strand-specific libraries with target enrichment is a sensitive, generalized approach to pathogen sequencing and transcriptome profiling. Using this method, we recovered 13 (76%) complete human respiratory syncytial virus (RSV) genomes from 17 clinical respiratory samples, reconstructed the phylogeny of the infecting viruses, and detected differential gene expression between two RSV subgroups, specifically, a lower expression of the P gene and a higher expression of the M2 gene in RSV-A than in RSV-B. This methodology can help to relate viral genetics to clinical phenotype and facilitate ongoing population-level RSV surveillance and vaccine development