Revaccination with Live Attenuated Vaccines Confer Additional Beneficial Nonspecific Effects on Overall Survival: A Review

• Live vaccines may have beneficial nonspecific effect protecting against more than the target disease.
• Revaccination with vaccines against measles, tuberculosis, polio and smallpox should have limited effect on survival.
• Nonetheless, revaccination with these vaccines indicate major reductions in all-cause mortality.Live vaccines against measles, tuberculosis, polio, and smallpox reduce mortality more than explained by prevention of the target-disease. Hence, these vaccines train the immune system to protection against unrelated infections. The beneficial nonspecific effect is enhanced when vaccination takes place in presence of maternal immunity. We therefore examined whether revaccination with the live vaccines against measles, tuberculosis, polio and smallpox boosted their beneficial nonspecific effects. Though limited, existing scientific literature supports that revaccination enhances the beneficial nonspecific effects of these four vaccines. The implications are potentially major; overall mortality could be reduced significantly with increasing use of revaccination with live vaccines.

BackgroundLive vaccines against measles (MV), tuberculosis (BCG), polio (OPV) and smallpox reduce mortality more than explained by target-disease prevention. The beneficial nonspecific effects (NSEs) of MV are strongest when MV is given in presence of maternal antibodies. We therefore hypothesised that revaccination in presence of prior immunity enhances beneficial NSEs.MethodsLiterature search for studies of revaccination and mortality.FindingsIn two randomised trials (RCTs), two doses versus one dose of MV reduced all-cause mortality by 63% (95% CI: 23–83%) from 9 to 18 months of age. In a quasi-experimental study two doses before and after 9 months compared with one dose of MV after 9 months of age reduced mortality by 59% (25–81%). BCG-revaccination significantly enhanced BCG's effect against overall child mortality in two RCTs. In a natural experiment study of OPV campaigns over a 13-year-period in Guinea-Bissau, each additional dose of OPV was associated with a 13% (4–21%) reduction in mortality rate. The beneficial NSEs of smallpox vaccination for survival increased significantly with the number of smallpox vaccination scars.InterpretationRevaccination with live vaccines led to substantial reductions in overall mortality. These findings challenge current understanding of vaccines and may explain the beneficial effects of campaigns with live vaccines.