Table 4.

Possible modifiers of the effect of early measles vaccination on mortality

Epidemiological observations	Comparable biological data
Early OPV enhances the beneficial effect of early MV at 4–5 months of age (this paper)	Cross-stimulation has been shown to enhance immunological responses, eg, early BCG primes for a stronger specific immune response to hepatitis B vaccine (HBV) and OPV vaccinations.6 7 On the other hand, we have also observed that OPV given with BCG at birth reduces the specific immune response to BCG. Effect of cross-stimulation on mortality has not been studied.
Campaign-OPV-before-early MV reduces the beneficial effect of early MV (this paper). Campaign-OPV may have both reduced the mortality level in the 1-dose group and increased the mortality rate slightly in the 2-dose MV group, resulting in an overall elimination of the differential (beneficial) effect of early MV (this paper).	The sequence or combination of early life vaccines, including BCG, OPV, DTP, and HBV, often have an impact on subsequent mortality.19 28 29 The underlying biological mechanisms have not been studied.
Campaign-OPV-after-early MV (and usually after a second dose of MV) following previous OPV before early MV reduces the benefit of early MV by reducing mortality more strongly in the 1-dose MV group or by increasing mortality in the 2-dose group (this paper).	Several studies have shown that re-exposure to the same antigen enhances the beneficial effect, eg, BCG, MV and Vaccinia. Such beneficial boosting effects of OPV could be more pronounced in the 1-dose group which had more to gain. The underlying biological mechanisms have not been studied.
Presence of maternal measles antibodies enhances the beneficial effect of early MV at 4.5 months of age20	This has been shown in animal studies but has not been studied for other human pathogens.30
Neonatal vitamin A (NVAS) reduced the beneficial effect of early MV at 4.5 months of age3. As with campaign-OPV, NVAS may have both reduced the mortality level in the one-dose group and increased the mortality rate slightly in the 2-dose MV group, resulting in an overall elimination of the differential (beneficial) effect of early MV.11	In vitro studies have shown that vitamin A induces innate immune tolerance. Providing vitamin A can abrogate the innate immune training induced by BCG.31
DTP after early MV associated with increased mortality for females19	Numerous studies have shown that DTP and other inactivated vaccines administered after MV reduced or removed the beneficial non-specific effects of MV.19 29 The underlying biological mechanisms have not been studied.

DTP, diphtheria-tetanus-pertussis; MV, measles vaccine; NVAS, neonatal vitamin A supplementation; OPV, oral polio vaccine.