Non-specific immunological effects of selected routine childhood immunisations: systematic review.

Wednesday, 2nd of November 2016

BMJ. 2016 Oct 13;355:i5225. doi: 10.1136/bmj.i5225.

Non-specific immunological effects of selected routine childhood immunisations: systematic review.

Kandasamy R¹ Voysey M² McQuaid F³ de Nie K³ Ryan R³ Orr O³ Uhlig U⁴ Sande C³ OConnor D³ Pollard AJ³.

Author information

Abstract

OBJECTIVE:

 To identify and characterise non-specific immunological effects after routine childhood vaccines against BCG measles diphtheria pertussis and tetanus.

DESIGN:

 Systematic review of randomised controlled trials cohort studies and case-control studies.

DATA SOURCES:

 Embase PubMed Cochrane library and Trip searched between 1947 and January 2014. Publications submitted by a panel of experts in the specialty were also included.

ELIGIBILITY CRITERIA FOR SELECTING STUDIES:

 All human studies reporting non-specific immunological effects after vaccination with standard childhood immunisations. Studies using recombinant vaccines no vaccine at all or reporting only vaccine specific outcomes were excluded. The primary aim was to systematically identify assemble and review all available studies and data on the possible non-specific or heterologous immunological effects of BCG; measles; mumps measles and rubella (MMR); diphtheria; tetanus; and pertussis vaccines.

RESULTS:

 The initial search yielded 11 168 references; 77 manuscripts met the inclusion criteria for data analysis. In most included studies (48%) BCG was the vaccine intervention. The final time point of outcome measurement was primarily performed (70%) between one and 12 months after vaccination. There was a high risk of bias in the included studies with no single study rated low risk across all assessment criteria. A total of 143 different immunological variables were reported which in conjunction with differences in measurement units and summary statistics created a high number of combinations thus precluding any meta-analysis. Studies that compared BCG vaccinated with unvaccinated groups showed a trend towards increased IFN-γ production in vitro in the vaccinated groups. Increases were also observed for IFN-γ measured after BCG vaccination in response to in vitro stimulation with microbial antigens from Candida albicans tetanus toxoid Staphylococcus aureas lipopolysaccharide and hepatitis B. Cohort studies of measles vaccination showed an increase in lymphoproliferation to microbial antigens from tetanus toxoid and C albicans Increases in immunogenicity to heterologous antigens were noted after diphtheria-tetanus (herpes simplex virus and polio antibody titres) and diphtheria-tetanus-pertussis (pneumococcus serotype 14 and polio neutralising responses) vaccination.

CONCLUSIONS:

 The papers reporting non-specific immunological effects had heterogeneous study designs and could not be conventionally meta-analysed providing a low level of evidence quality. Some studies such as BCG vaccine studies examining in vitro IFN-γ responses and measles vaccine studies examining lymphoproliferation to microbial antigen stimulation showed a consistent direction of effect suggestive of non-specific immunological effects. The quality of the evidence however does not provide confidence in the nature magnitude or timing of non-specific immunological effects after vaccination with BCG diphtheria pertussis tetanus or measles containing vaccines nor the clinical importance of the findings.

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