Chapter 3 - Non-specific Effects of Vaccines

Abstract

This chapter addresses the broader effects of vaccines [that have an immunological and clinical impact] beyond protection against their target pathogen. Evidence from clinical studies is reviewed, focusing on how different vaccines influence all-cause mortality rates, prevent or treat infections other than those for which they are intended, prevent allergic and atopic diseases, influence the clinical course of autoimmune and immune-mediated diseases, prevent or treat malignancies, and influence other conditions, such as neurodegenerative diseases. Factors that might influence the non-specific effects of vaccines are also discussed. These include: the differences observed following live-attenuated vaccines compared with non-live vaccines; the importance of the sequence of administration of vaccines, whether it is a live-attenuated vaccine or a non-live vaccine that is given last, and whether they are given simultaneously or separately; and sex, age at vaccination, pre-existing immunity, predisposition and clinical setting. The time to onset and duration of non-specific effects reported after vaccination are also discussed, as well as some of the methodological issues and limitations of clinical trials, focusing on BCG studies. The immunological and molecular mechanisms that may underlie the non-specific effects of vaccines are outlined, in particular heterologous lymphocyte responses that occur through cross-reactive adaptive memory, and the innate immune memory that occur through reprogramming of innate immune responses (trained immunity). Finally, future perspectives and key unanswered questions are addressed, including challenges for future studies, implications that non-specific effects may have for vaccine trials and policy, and how non-specific effects could be exploited further to optimise the benefits of vaccination.