Human respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection in young children globally, but little is known about within-host RSV diversity. Here, we characterised within-host RSV populations using deep-sequencing data from 319 nasopharyngeal swabs collected during 2017–2020. RSV-B had lower consensus diversity than RSV-A at the population level, while exhibiting greater within-host diversity. Two RSV-B consensus sequences had an amino acid alteration (K68N) in the fusion (F) protein, which has been associated with reduced susceptibility to nirsevimab (MEDI8897), a novel RSV monoclonal antibody under development. In addition, several minor variants were identified in the antigenic sites of the F protein, one of which may confer resistance to palivizumab, the only licensed RSV monoclonal antibody. The differences in within-host virus populations emphasise the importance of monitoring for vaccine efficacy and may help to explain the different prevalences of monoclonal antibody-escape mutants between the two subgroups.

The objectives of this study were to evaluate the kinetics of antibody decline through childhood in a longitudinal study of a single cohort following serogroup C meningococcal (MenC) vaccine immunization in early childhood and to calculate the proportion of 11 to 13 year olds with protective levels of bactericidal antibody 10 years after immunization. United Kingdom children aged 11 to 13 years in 2010 who had previously taken part in a longitudinal study at the Oxford Vaccine Group had blood samples drawn between 2001 and 2010. Sera from each time point were analyzed for the MenC serum bactericidal antibody titer using a baby rabbit complement (rSBA) assay. The median age at MenC immunization was 21 months (range, 1 year 3 months to 3 years 9 months). The MenC rSBA geometric mean titer (GMT) at age 3.5 to 5 years was 8.0 (95% confidence interval, 6.5 to 9.9; n ‫؍‬ 287). By age 11.5 to 13.5 years, the rSBA GMT had declined to 3.3 (2.5 to 4.4; n ‫؍‬ 98). The percentage of children with rSBA titers of >1:8 (the threshold for protection) also declined from 38% (35% to 41%) to 15% (12% to 19%). We concluded that MenC rSBA titers wane rapidly following vaccination in early childhood and continue to decline into the second decade of life. Since nasopharyngeal colonization in adolescents probably provides the major reservoir for MenC in the population, declining immunity in this cohort is of concern. Sustaining high levels of antibody through booster vaccination in this cohort is likely necessary to avoid a resurgence of disease in the decade ahead.

all at affiliation 2); Miles W. Carroll (at affiliation 7); and Annina Schmid (at affiliation 9). Also, two author names (Rachel Varughes and Gary Mallett) were incorrect; the correct names are 'Rachel Varughese' and 'Garry Mallett' (respectively). The errors have been corrected in the HTML and PDF versions of the article.

Introduction Meningococcal serogroup C (MenC) conjugate vaccines are used routinely for infant immunisation in Canada and Europe. Quadrivalent serogroup A, C, W−135 and Y meningococcal (MenACWY) conjugate vaccines are licensed in Europe and North America, and recommended for routine immunisation of adolescents in the United States. Methods In an open-label, randomised controlled trial in the UK and Canada, we evaluated the persistence of immune response at 40 and 60 months of age after different schedules of two MenACWY-CRM conjugate vaccine formulations administered in infancy with MenC conjugate and MenACWY polysaccharide vaccines at 12 months of age. Two control groups were also recruited at 60 months, who had been immunised as infants or toddlers with MenC vaccines according to country-specific schedules. Results 382 children enrolled in 12 groups (22 to 40 per group) were followed up. By age 60 months, 3-11% of children primed and boosted with MenACWY-CRM had serum bactericidal antibody (using human complement [hSBA]) titres ≥1:8 against serogroup A meningococci, 14-45% against serogroup C, 57-84% against serogroup W-135 and 42-69% against serogroup Y. These proportions were similar for children primed with MenC and boosted with MenACWY-CRM except for serogroup C (59%). In age-matched control children at 60 months of age, percentages with hSBA titres ≥1:8 were 0-3%, 29-53%, 33-36% and 10-29% against serogroups A, C, W-135 and Y, respectively. Conclusions Immune responses against all serogroups wane following infant immunisation with MenACWY-CRM vaccines, most markedly against serogroup A. Better persistence of serogroup C hSBA titres was observed in schedules with MenC conjugate vaccine priming doses, however use of a booster MenACWY conjugate vaccine could provide broader protection against meningococcal disease.

Aims Combining the licensed Haemophilus influenzae type b (Hib) and serogroup C meningococcal (MenC) conjugate vaccine (Hib-MenC-TT) and DTaP-IPV vaccine could reduce the number of injections needed to administer the United Kingdom routine infant immunisation schedule. We aimed to demonstrate immunologic non-inferiority for Hib and MenC using a 6-in-1 combination vaccine (DTPa-IPV/Hib-MenC-TT) compared to a schedule using DTPa-IPV-Hib-TT and MenC-CRM197 conjugate vaccines. Secondary objectives included demonstration of non-inferiority of diphtheria, tetanus and polio immunogenicity; persistence of immune response to all antigens at 12 months of age and the response to a 12 month Hib-MenC-TT booster. Methods Open-label, randomised, multi-centre, UK study. Combination group received DTPa-IPV/Hib-MenC-TT at 2, 3, 4 months. Control group received DTPa-IPV-Hib-TT at 2, 3, 4 months and MenC-CRM197 at 3, 4 months. Both groups received Hib-MenC-TT booster at 12 months. Concomitant vaccines: pneumococcal conjugate vaccine at 2, 4, 13 months; MMR at 13 months. Blood tests were performed at 4, 5, 12 and 13 months. Results 142 children were randomised in each group. 100 children were included in the according-to-protocol cohort for analysis of immunogenicity following the booster vaccine in the combination group; and 112 children in the control group. One month post-primary immunisations 100% of the combination group and 93.3 % of control children had anti-PRP IgG concentration ≥0.15 μg/mL. 96.2% and 100% respectively had rSBA-MenC titres ≥1:8. One month post-booster all children met these thresholds. At 13 months of age, anti-PRP geometric mean concentrations (with 95% confidence intervals) were 66.7 (53.3-83.5) in the combination group and 26.9 (20.9-34.6) in the control group (4.35 [3.51-5.39] and 3.04 [2.21-4.19] respectively at 5 months). rSBA-MenC geometric mean titres (GMTs) were 3062.9 (2421.2-3874.6) and 954.0 (761.3-1195.5) respectively (393.2 [292.5-528.7] and 3110.5 [2612-3704.2] respectively at 5 months). Conclusion Non-inferiority of DTPa-IPV/Hib-MenC-TT compared to DTPa-IPV-Hib-TT plus MenC-CRM197 was demonstrated. The lower rSBA-MenC GMTs after primary immunisations and greater booster responses in the combination group suggest that immune priming might be inversely related to post-primary antibody responses. Furthermore, greater immunogenicity of TT conjugates used in primary and booster MenC vaccines in this group may be important.