The impact of vaccines on heterologous adaptive immunity

Vaccines induce antigen-specific memory in adaptive immune cells that enables long-lived protection against the target pathogen. In addition to this, several vaccines have beneficial effects greater than protection against their target pathogen. These non-specific effects are proposed to be the result of vaccine-induced immunomodulation. In the case of bacille Calmette-Guérin (BCG) vaccine, this involves induction of innate immune memory, termed 'trained immunity', in monocytes and natural killer cells.

This review discusses current evidence for vaccine-induced immunomodulation of adaptive immune cells and heterologous adaptive immune responses.

The three vaccines that have been associated with changes in all-cause infant mortality: BCG, diphtheria-tetanus-pertussis (DTP) and measles-containing vaccines (MCV) alter T-cell and B-cell immunity. The majority of studies that investigated non-specific effects of these vaccines on the adaptive immune system report changes in numbers or proportions of adaptive immune cell populations. However, there is also evidence for effects of these vaccines on adaptive immune cell function and responses to heterologous stimuli. There is some evidence that, in addition to BCG, DTP and MCV, other vaccines (that have not been associated with changes in all-cause mortality) may alter adaptive immune responses to unrelated stimuli.

This review concludes that vaccines alter adaptive immune cell populations and heterologous immune responses. The non-specific effects differ between various vaccines and their effects on heterologous adaptive immune responses may also involve bystander activation, cross-reactivity and other as yet undefined mechanisms. This has major implications for future vaccine design and vaccination scheduling.