May-Lill Garly

Garly 1999
Garly, May-Lill. 1999. Specific and non-specific effects of standard-titre measles vaccine and the BCG vaccine. Bandim Health Project, Statens Serum Institut. University of Copenhagen.


The aims of the study was to investigate the feasibility of implementing an early two-dose measles vaccination schedule in a West African setting in terms of participation rate, measles vaccination coverage, vaccine efficacy, humoral and cell­mediated immune responses.

Children of 6 months of age were randomised to receive either two doses of standard-titre measles vaccine at 6 and 9 months of age or an inactivated polio vaccine at 6 months, and a standard­titre measles vaccine at 9 months of age. Blood samples were drawn at 6, 9 and 18 months of age, skin prick testing and testing of delayed-type hypersensitivity was performed on a sub-cohort at 7,5 months of age.

The participation rates within the study were high, at both 6 and 9 months of age around 86%, and the return rate was 93%. There was a 50% reduction in the risk of not being vaccinated by belonging to the two-dose group.

Among the two different strains of standard-titre measles vaccine used, the Edmonton-Zagreb (EZ) and the Schwarz (SW) measles vaccine, the EZ measles vaccine was shown to be more immunogenic in the presence of maternal antibodies than the SW vaccine. In contrast, the SW vaccine induced a higher level of antibodies than the EZ vaccine in the absence of maternal antibodies. Thus, the SW vaccine was found to be subject to the phenomenon blunting, where the first vaccination did not induce a satisfactory antibody response, and subsequent doses could not boost the antibodies to a higher level.

An early two-dose schedule was found to provide good protection against measles among infants below the normal age of vaccination (9 months). After 9 months of age there was no difference between having received one or two doses of measles vaccine. Preliminary data showed a significant interaction between number of doses and vaccine strain, i.e. two doses of EZ vaccine provided better protection against measles than one dose of EZ vaccine, and than one or two doses of SW vaccine. 

In terms of skin-prick testing, small children of 7,5 months of age were found not to be sensitized to common allergens yet.

In the study of delayed-type hypersensitivity, risk factors for allergy were defined. Data showed the BCG vaccine to be associated with less energy lo all the vaccine-related antigens studied. Within groups of antigen, which included the tuberculin reaction, children vaccinated with BCG after 1 month of age were less anergic than children vaccinated earlier. The DTP/OPV vaccine was associated with fewer allergies to vaccine-related antigens, which included diphtheria and tetanus. Furthermore, there was a higher prevalence of anergy in the rainy season and among sick children. Thus, the BCG vaccine was shown to have a non-specific effect towards less energy, which included other vaccine-related antigens than tuberculin per se.

Conclusion and future perspectives
The study showed that an early two-dose measles vaccination schedule was very well accepted, that participation and return rates were high, that vaccination coverage was higher with a two-dose than with a one-dose schedule, and that a two-dose schedule was more protective against measles than a one-dose schedule among infants below the normal age of vaccination.

A difference in immunogenicity between the standard-titre SW vaccine and the standard-titre EZ vaccine was demonstrated; the SW vaccine induced the highest measles antibody levels in the absence of maternal antibodies, whereas the EZ vaccine induced higher measles antibody levels in the presence of maternal antibodies.

Although the EZ vaccine could thus seem the best choice for an early two-dose Schedule, it is too early to draw such a conclusion, since cellular immunity and long-tem mortality will have to be taken into consideration. Such data will in the future be available from the Two-dose study of the standard-titre measles vaccine in Bissau.
The BCG vaccine was shown to have a non-specific effect towards less anergy, suggesting a stimulatory effect of the BCG vaccine on the cellular immune system among infants.

In conclusion, much remains to be learned about vaccines, also about the vaccines, which have already been used for decades. Although vaccinations in general are preventing millions of deaths worldwide every year, many questions still remain to be answered. Further studies should be perfumed in the field of specific and non-specific effects of vaccines, since this could have important implications for lowering childhood morbidity and mortality in developing countries.