Preterm infants are more likely to experience severe respiratory syncytial virus (RSV) disease compared to term infants. The reasons for this are multi-factorial, however their immature immune system is believed to be a major contributing factor. We collected cord blood from 25 preterm (gestational age 30.4-34.1 weeks) and 25 term infants (gestation age 37-40 weeks) and compared the response of cord blood mononuclear cells (CBMCs) to RSVA and RSVB stimulation using neutralising assays, high-dimensional flow cytometry, multiplex cytokine assays and RNA-sequencing. We found that preterm and term infants had similar maternally derived neutralising antibody titres to RSVA and RSVB. Preterm infants had significantly higher myeloid dendritic cells (mDC) RSV infection compared to term infants. Differential gene expression analysis of RSVA stimulated CBMCs revealed enrichment of genes involved in cytokine production and immune regulatory pathways involving IL-10, IL-36γ, CXCL1, CXCL2, SOCS1 and SOCS3 in term infants, while differentially expressed genes (DEGs) in preterm infants were related to cell cycle (CDK1, TTK, ESCO2, KNL1, CDC25A, MAD2L1) without associated expression of immune response genes. Furthermore, enriched genes in term infants were highly correlated suggesting an increased co-ordination of their immune response to RSVA. When comparing DEGs in preterm and term infants following RSVB stimulation, no differences in immune response genes were identified. Overall, our data suggests that preterm infants have a more restricted immunological response to RSVA compared with term infants. While further studies are required, these findings may help to explain why preterm infants are more susceptible to severe RSV disease and identify potential therapeutic targets to protect these vulnerable infants. Murdoch Children's Research Institute Infection and Immunity theme grant.

The use of pneumococcal conjugate vaccine (PCV) schedules with fewer doses are being considered to reduce costs and improve access, particularly in low- and middle-income countries. While several studies have assessed their immunogenicity, there are limited data on their potential for long-term immune protection, as assessed by pneumococcal serotype-specific memory B cell (B_mem) responses. This current study reports secondary outcome data that aims to compare B_mem responses following reduced-dose (0 + 1 and 1 + 1) schedules of PCV10 and PCV13 in Vietnamese infants from our randomised-controlled trial (trial registration number NCT03098628). Following vaccination at 12 months of age, B_mem levels for most serotypes peaked seven days post-vaccination and were higher in magnitude for the 1 + 1 than 0 + 1 schedules and for PCV13 than PCV10. Furthermore, B_mem did not wane as rapidly as IgG levels by 24 months of age. Further studies are needed to assess the use of B_mem as markers of long-term protection against pneumococcal carriage and disease, which is crucial to generate data for immunisation program decision-making.

Our goal was to describe Invasive Meningococcal Disease (IMD) in Southern Vietnam over the last 10 years. We characterized 109 Neisseria meningitidis strains in Southern Vietnam isolated between 1980s to 2021, that were collected from IMD (n = 44), sexually transmitted infections (n = 2), and healthy carriage (n = 63). IMD were confirmed by bacterial culture and/or real-time polymerase chain reaction at the national reference laboratory in Pasteur Institute of Ho Chi Minh City (PIHCM). Antimicrobial resistance was determined on 31 IMD and two sexually transmitted infection isolates with E-test for chloramphenicol (CHL), penicillin (PEN), ciprofloxacin (CIP), ceftriaxone (CRO), and rifampicin (RIF). Sequencing was performed for analyzing of multilocus-sequence-typing (MLST), porA, fetA, and antibiotic resistance genes, including gyrA, penA, and rpoB. The incidence rate during this period was 0.02 per 100,000 persons/year. Serogroup B accounted for over 90% of cases (50/54). ST-1576 were mainly responsible for IMD, 27/42 MLST profiles, and associated with CHL resistance. Resistance was prevalent among IMD isolates. Thirteen were resistant to CHL (minimum inhibitory concentration [MIC] ≥16 mg/l), 12 were intermediate to PEN (MIC between 0.19 and 0.5 mg/l), and five were CIP-resistant (MIC between 0.19 and 0.5 mg/l). Particularly, one was non-susceptible to CRO (MIC at 0.125 mg/l), belonging to ST-5571 lineage. The resistance was due to carrying resistant alleles of penA and gyrA genes, and catP gene. Notably, seven isolates were resistant/non-susceptible to two or more antibiotics. Our results suggest the persistence of the circulating ST-1576 in Southern Vietnam, with a spread of antimicrobial resistance across the community.

Preterm infants are more susceptible to severe bacterial and viral infectious diseases than their full-term counterparts. A major contributor to this increased susceptibility may be due to differences in their ability to respond to pathogens. While studies have demonstrated altered bacterial Toll-like receptor (TLR) responses, there is limited data on viral TLR responses in preterm infants. In this study, cord blood mononuclear cells (CBMCs) from 10 moderately preterm (30.4–34.1 wGA), 10 term (37–39.5 wGA) infants, and 5 adults were stimulated with TLR2 (lipoteichoic acid), TLR3 (poly I:C), TLR4 (lipopolysaccharide), TLR7/8 (R848), and TLR9 (CpG-ODN 2216) agonists. Following stimulation, the cellular response was measured by intracellular flow cytometry to detect cell-specific NF-κB (as a marker of the inflammatory response), and multiplex assays were used to measure the cytokine response. This study found that preterm and term infants exhibit very similar baseline TLR expression. In response to both bacterial and viral TLR agonists comparing cell-specific NF-κB activation, preterm infants exhibited increased monocyte activation following LTA stimulation; however, no other differences were observed. Similarly, no difference in cytokine response was observed following stimulation with TLRs. However, a stronger correlation between NF-κB activation and cytokine responses was observed in term infants following poly I:C and R848 stimulation compared to preterm infants. In contrast, despite similar TLR expression, adults produced higher levels of IFN-α following R848 stimulation compared to preterm and term infants. These findings suggest preterm and term infants have a similar capacity to respond to both bacterial and viral TLR agonists. As preterm infants are more likely to develop severe infections, further research is required to determine the immunological factors that may be driving this and develop better interventions for this highly vulnerable group.

Streptococcus pneumoniae (the pneumococcus) is one of the main causes of childhood mortality. Understanding pneumococcal serotype and lineage distribution in children is important for vaccine decision-making. We undertook a secondary analysis of nasopharyngeal swabs collected from unvaccinated children as part of pneumococcal vaccine studies to provide a comprehensive picture of pneumococcal carriage epidemiology in Vietnamese children during the first 60 months of life. We analysed 4375 nasopharyngeal swabs from unvaccinated children to assess overall and vaccine-type pneumococcal carriage at 6, 12, 18, 24, and 60 months of age. For the latter three age groups, serotype distribution and genetic lineages (Global Pneumococcal Sequence Cluster, GPSCs) were described overall and by age. We also evaluated the prevalence of antimicrobial resistance (AMR) genes and multi-drug resistance (MDR), comparing vaccine-type and non-vaccine-type pneumococci. Overall pneumococcal carriage was 21·7% (952/4375) with a total of 27 serotypes detected. Serotype coverage was similar across products Pneumosil (68·6% [95% CI 65·5–71·7%], 595/867), Prevenar13 (70·0% [95% CI 67·0–73·1%], 607/867), and Vaxneuvance (70·0% [95% CI 67·0–73·1%], 607/867), and lower for Synflorix (41·5% [95% CI 38·2–44·8%], 360/867) p < 0·05 vs Pneumosil, Prevenar13 or Vaxneuvance. In total, 2444 swabs were tested at 18, 24, and 60 months. Thirty distinct GPSCs were identified, with their distribution remaining stable across these ages. AMR genes were highly prevalent, detected in 98·9% (360/364) of samples. Synflorix provided lower serotype coverage than other PCVs, largely driven by the prevalence of serotype 6A, which is not included in Synflorix formulation. Serotype, lineage distribution, and prevalence of AMR genes across the sampled age groups remained consistent, indicating that these distributions are broadly representative of young unvaccinated children, helping to guide optimal approaches for pneumococcal surveillance in low- and middle-income countries. 10.13039/501100000925 National Health and Medical Research Council , 10.13039/100000865 Bill & Melinda Gates Foundation , 10.13039/100014555 Murdoch Children's Research Institute .

Correlates of protection for pneumococcal carriage, a precursor for invasive pneumococcal disease, are not well defined. The relationship between memory B cells (B_mem) with carriage remains unclear. We assessed serotype-specific B_mem, IgG and opsonophagocytic (OPA) responses following different infant schedules of 10-valent pneumococcal conjugate vaccine (PCV10, Synflorix) and their association with pneumococcal carriage. We analysed secondary outcome data from a phase II/III randomised controlled trial in Viet Nam (trial registration NCT01953510). Infants received PCV10 in a 3+1 (2-3-4-9 months), 3+0 (2-3-4 months) or 2+1 (2-4-9.5 months) schedule. Serotype-specific B_mem, IgG and OPA were measured at 10 months (all) and 18 months (B_mem and IgG only). Carriage was assessed from nasopharyngeal swabs at 12-18-24 months with additional carriage episodes identified by seroincidence. Associations between immunological parameters at 10 months and subsequent carriage were evaluated using multivariable logistic regression. At 10 months, B_mem levels were similar across vaccine arms, but IgG and OPA were higher in the 3+1/2+1 than 3+0 arm. At 18 months, B_mem and IgG waned for most serotypes in all vaccine arms. There were minimal associations between the immunological parameters and subsequent carriage. Only IgG was negatively associated with serotype 19A carriage, when defined as carriage and/or seroincidence ≥2-fold (odds ratio: 0.31, 95% confidence interval: 0.10-0.94, p=0.038), and carriage and/or seroincidence of any increase (odds ratio: 0.13, 95% confidence interval: 0.04-0.40, p<0.001). We found no substantive evidence linking B_mem, IgG and OPA with pneumococcal carriage. Larger studies are needed to identify associations between different immunological parameters and carriage.