The Oxford Vaccine Group has produced research over the past 30 years to support major developments in the childhood immunisation programme, particularly informing global policy on pneumonia and meningitis programmes, the scheduling of vaccines and the use of combination vaccines for infants and toddlers.

Studies on anti-meningococcal immunity initially identified poor quality antibody responses in young children (Pollard & Levin, Lancet 2000) and then provided new insight into immunity after vaccination with polysaccharide and conjugate vaccines (Kelly et al, Blood 2006), with the first descriptions of the nature and kinetics of the plasma and memory B cell response to polysaccharide and conjugate vaccines in infancy.

We also conducted intricate studies to show the relationship between germinal centre priming in infants and the magnitude of the immune response, suggesting that strategies that favour production of memory B cells, rather than antibody-producing plasma cells, might lead to better magnitude and persistence of immune responses in infancy.

Evaluation of the group C meningococcal vaccine demonstrated poor persistence of immunity after early childhood and that young children had become susceptible again, leading to a change in policy and introduction of meningococcal booster vaccines for adolescents in many countries including the UK.

We also contributed to understanding of the role of nasopharyngeal colonization, the potential for control of transmission and induction of herd immunity with meningococcal and pneumococcal vaccines. Studies on scheduling vaccination showed that reduced dose schedules were as immunogenic as standard schedules, leading to a reduction in the numbers of doses administered for infants.

The OVG led the first global infant trials of a quadrivalent meningococcal vaccine, a combination Haemophilus influenzae type b-serogroup C meningococcal vaccine, and a serogroup B meningococcal candidate vaccine (MenB, Bexsero, GSK vaccines), supporting the eventual licensure of each of these products. The group also led the pan-European phase 3 study of the MenB vaccine which supported its introduction for all infants in the

UK in 2015. We also showed how immunity to this vaccine persists through early childhood but fades by adolescence and provided novel insight into the genetic control of vaccine reactions and persistence of immunity using GWAS.

Around 600,000 infants each year receive meningococcal vaccines from the NHS which prevent up to 1,000 cases of meningitis per annum in the UK alone, directly linked to OVGs research. We have designed two entirely novel meningococcal vaccines through preclinical development to ongoing early phase studies in humans.

Furthermore, the OVG led ground-breaking studies on epidemiology, immunity and immunisation against pneumococcus, responsible for nearly 300,000 paediatric deaths globally. The work has predominantly been conducted in the UK and Nepal, where we run surveillance for invasive bacterial disease, funded by WHO and Gavi for 18 years, embedding intervention studies in the programme to assess vaccine impact, informing global policy.

Our work on interchangeability of different pneumococcal vaccines as a booster for toddlers is also cited in WHO guidance. Extensive international studies conducted by OVG have shown the impact of vaccines on nasopharyngeal carriage of pneumococci documenting changes in serotype distribution and informing vaccine programmes. Our work has contributed to an extensive series of host and bacterial genetic studies showing genes associated with meningitis and molecular epidemiology of S. pneumoniae. Furthermore, in an extensive series of laboratory studies, we investigated immunity to polysaccharide and conjugate vaccines and showed that antigen-specific B cells were depleted by plain polysaccharide vaccines but not conjugate vaccines, reducing responsiveness to subsequent vaccine doses.