Non-specific effects of vaccines: plausible and potentially important, but implications uncertain

Abstract

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.

The immunomodulatory effects of measles‐mumps‐rubella vaccination on persistence of heterologous vaccine responses

“…It is proposed that vaccines, particularly live‐vaccines such as Bacillus Calmette‐Guérin (BCG) and measles‐containing vaccines (MCV), have heterologous (“nonspecific”) immunomodulatory effects . These are effects induced by vaccines beyond protection against their targeted disease.…”

“…It is proposed that vaccines, particularly live-vaccines such as Bacillus Calmette-Gu erin (BCG) and measles-containing vaccines (MCV), have heterologous ("nonspecific") immunomodulatory effects. [1][2][3][4] These are effects induced by vaccines beyond protection against their targeted disease. The reduced mortality has been attributed to decreased deaths from respiratory illnesses, diarrhea and malnutrition.…”

Long-Term Reduction in Hyperglycemia in Advanced Type 1 Diabetes—The Value of Induced Aerobic Glycolysis by BCG Vaccinations

“…4 BCG vaccination confers a survival advantage in low birthweight infants against mortality from a diversity of infections unrelated to tuberculosis, and BCG vaccinations in healthy populations confer long term survival advantages. [13][14][15][16] Many autoimmune NOD (non-obese diabetic) murine studies have shown a beneficial effect of BCG or CFA (Complete Freund's Adjuvant) in preventing the onset of autoimmune diabetes and even reversing full blown established disease in mice. 17,18 The NOD mouse is a well-studied spontaneous model of autoimmune diabetes and mimics some but not all the features of human disease.…”

São Paulo School of Advanced Sciences on Vaccines: an overview

“…There is substantial evidence that these effects are generally stronger in females than in males [69]. Another idea is that the vaccine-mediated heterologous protection would be partly mediated by heterologous effects on the adaptive immunity and by potentiating innate immune responses through epigenetics [70]. Nevertheless, some vaccines present negative heterologous effects, which end up reinforcing anti-vaccine movements.…”