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This study is now complete.


This study aims to combine data from randomised controlled trials of vaccines administered to infants and young children to assess factors which influence the immune response to vaccination. Optimising the infant immunisation programme will provide better protection against disease, without increasing costs for the NHS.

Why is this important?

Vaccination is a key area of NHS policy and one of the most cost-effective public health interventions for protecting the population from disease. There are many factors which can impact the way a child’s immune system responds to vaccination, such as the age at which the first vaccine is delivered, the sex of the child and the spacing between doses. Variation in these and other factors leads to better immunity in some children than others. Infants are provided with a degree of protection against disease in the first few months of life due to an inherited antibody from their mother. This maternally-derived antibody wanes over time but whilst still circulating can interfere with the way the infant’s immune system responds to vaccination. The current programme to immunise mothers in the third trimester of pregnancy is one way to enhance protection for infants, however this may also have negative impacts on the infant’s response to their vaccines.

A clearer understanding of these influences on vaccine induced immunity may enable further optimisation of vaccination programmes to enhance the degree of protection afforded by the routine infant immunisation schedule.


Individual participant data from approximately 170 randomised controlled trials assessing the immunogenicity, safety and efficacy of vaccines in infants and healthy young children will be used for these investigations. Trials will be included which administered the following vaccines as either the randomised intervention or as a co-administered routine vaccine: diphtheria toxoid; tetanus toxoid; pertussis (acellular or whole-cell); polio (inactivated or oral); hepatitis B; Haemophilus influenzae type b; meningococcal; pneumococcal; rotavirus; measles; mumps; rubella; varicella.


Sex-dependent immune responses to infant vaccination: an individual participant data meta-analysis of antibody and memory B cells.
Voysey M, Barker CIS, Snape MD, Kelly DF, Truck J, Pollard AJ
Vaccine 2016; doi: 10.1016/j.vaccine.2016.02.036 (In Press)

Prevalence and decay of maternal pneumococcal and meningococcal antibodies: a meta-analysis of type-specific decay rates. 
Voysey M, Pollard AJ, Sadarangani M, Fanshawe TR.
Vaccine 2017; 35(43): 5850-5857.

The influence of maternal antibody and age at vaccination on infant vaccine responses: an analysis of immunity from 7630 children.
Voysey M, Kelly DF, Fanshawe TR, Perera R, Pollard AJ.
JAMA Pediatrics 2017: 171(7):637-646.

Computing threshold antibody levels of protection in vaccine clinical trials: an assessment of methodological bias.
Voysey M, Sadarangani M, Pollard AJ, Thorson S, Fanshawe TR.
PLoS ONE 2018; 13(9): e0202517.

Use of weighted multivariate estimates in trials of multi-serotype vaccines to simplify interpretation of treatment differences.
Voysey M, Pollard AJ, Perera R, Shrestha S, Ansari I, Thorson S, Fanshawe TR.
PLoS ONE 2018; 13(4): e0196200.

Further information:

Full project title:
Assessing sex-differences and the effect of timing of vaccination on immunogenicity, reactogenicity and efficacy of vaccines in young children: an individual participant data meta-analysis of randomised controlled trials.

Length of project:
4 years



NIHR Doctoral Research Fellowship