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Non-specific effects of vaccines: plausible and potentially important, but implications uncertain
  1. Andrew J Pollard1,2,
  2. Adam Finn3,
  3. Nigel Curtis4
  1. 1 Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK
  2. 2 NIHR Oxford Biomedical Research Centre, Oxford, UK
  3. 3 Bristol Children’s Vaccine Centre, University of Bristol, Bristol, UK
  4. 4 Department of Paediatrics, The University of Melbourne and Murdoch Childrens Research Institute, Royal Children’s Hospital Melbourne, Parkville, Victoria, Australia
  1. Correspondence to Professor Andrew J Pollard, Children’s Hospital, Oxford OX3 9DU, UK; andrew.pollard{at}


Non-specific effects (NSE) or heterologous effects of vaccines are proposed to explain observations in some studies that certain vaccines have an impact beyond the direct protection against infection with the specific pathogen for which the vaccines were designed. The importance and implications of such effects remain controversial. There are several known immunological mechanisms which could lead to NSE, since it is widely recognised that the generation of specific immunity is initiated by non-specific innate immune mechanisms that may also have wider effects on adaptive immune function. However, there are no published studies that demonstrate a mechanistic link between such immunological phenomena and clinically relevant NSE in humans. While it is highly plausible that some vaccines do have NSE, their magnitude and duration, and thus importance, remain uncertain. Although the WHO recently concluded that current evidence does not justify changes to immunisation policy, further studies of sufficient size and quality are needed to assess the importance of NSE for all-cause mortality. This could provide insights into vaccine immunobiology with important implications for infant health and survival.

  • Tropical Paediatrics
  • Infectious Diseases
  • Immunisation

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  • Competing interests AJP leads academic trials or publicly funded research on vaccines. A grant to Oxford University from Okairos to study respiratory syncytial vaccines ended in 2016. His department received unrestricted educational grants from Pfizer/GSK/AstraZeneca in July 2016 for a course on Infection and Immunity in Children. Other investigators in the Department conduct research funded by vaccine manufacturers. AJP chairs the UK Department of Health’s Joint Committee on Vaccination an Immunisation and the scientific advisory group on vaccines for the European Medicines Agency and is a member of the WHO’s SAGE. He previously contributed to the WHO systematic review on non-specific immunological effects of vaccines. AF undertakes research studies and trials of vaccines funded by governments, charities and industry. He is a member of the UK Department of Health’s Joint Committee on Vaccination, Chair of the WHO European Technical Advisory Group of Experts in which capacity he attends SAGE and President of the European Society for Paediatric Infectious Diseases, which receives sponsorship for its annual meeting from vaccine manufacturers. NC is leading a large randomised controlled trial (RCT) of BCG in infants ( identifier NCT01906853). He is a member of the WHO SAGE Working Group on BCG vaccines. He is a board member of the European Society for Paediatric Infectious Diseases, which receives sponsorship for its annual meeting from vaccine manufacturers.

  • Provenance and peer review Commissioned; externally peer reviewed.

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