Non-specific effects of vaccination in England

Application Number
Lay Summary

Some research suggests that vaccination not only protects against the disease that the vaccine targets, but may also have broader 'non-specific effects'. The hypotheses are that live vaccines (containing a weakened form of the virus, e.g. measles-mumps-rubella (MMR) vaccine or BCG) could provide wider protection against other infections, but this potential extra benefit is diminished by also giving inactivated (non-live) vaccines such as diphtheria, tetanus and pertussis (DTP). However, evidence for non-specific effects of vaccines is unclear. This study will investigate whether the frequency of infections is reduced in young children who receive live vaccines, and whether this effect is modified by giving inactivated vaccines. We will look at the effects of two live vaccines (BCG, given near birth, and MMR, given to toddlers) and the inactivated vaccines given to infants and toddlers (the 5-in-1 DTP-polio-Hib vaccine, Meningitis C and pneumococcal vaccines). Frequency of infections will be investigated a) in infancy, comparing individuals' risk of infection after receiving BCG with their risk after additionally receiving inactivated vaccines, and b) in the second year of life before and after receiving MMR, for two time periods: up to August 2006 (MMR given alone), and September 2006 onwards (MMR given alongside inactivated vaccines).

Technical Summary

This project will investigate aspects of 'non-specific effects' of vaccination; the hypothesised associations between live vaccines and a reduction in the number of infections, and between inactivated vaccines and an increase in the number of infections. Investigations will, in part, take advantage of change in vaccine schedules over time, and thus changes in the order in which live and inactivated vaccines are given. We will use the self-controlled case series method to compare the within-person relative incidence of a range of infections after receipt of inactivated vaccines compared to incidence after live vaccines. First, among infants given BCG (live) vaccine shortly after birth, we will investigate the relative incidence of infections in the first year of life, comparing incidence before and after receipt of the primary schedule of inactivated vaccines. Second, we will analyse the relative incidence of infections in the second year of life before and after receipt of MMR (live) vaccine, and we will compare whether this effect varies between two time periods; up to August 2006 when only MMR vaccine was given, and September 2006 onwards when MMR (live), pneumococcal conjugate vaccine (inactivated) and Meningitis C/Hib (inactivated) vaccines were given at the same time.

Health Outcomes to be Measured

We will examine a range of infection groups, recorded in either CPRD or in HES. These will include upper and lower respiratory tract infections, urinary tract infections, acute gastroenteritis, joint and bone infections, skin infections, neurological infections, eye infections, other bacterial and viral infections, and sepsis. These will be defined using Read and ICD10 code lists, updating the existing code lists we have used in previous ISAC approved studies of infections (for example, ISAC protocols 09-061RA, 11_033A, 15_146). The primary outcome will be any infection; we will then look at individual infection groups (study power permitting).


Helen McDonald - Chief Investigator - London School of Hygiene & Tropical Medicine ( LSHTM )
Jemma Walker - Corresponding Applicant - London School of Hygiene & Tropical Medicine ( LSHTM )
Anthony Scott - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Elizabeth Miller - Collaborator - Health Protection Agency - HPA
Heather Whitaker - Collaborator - Public Health England
Julia Stowe - Collaborator - Public Health England
Liam Smeeth - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Nick Andrews - Collaborator - Public Health England


HES Admitted Patient Care;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation