Are two doses of measles vaccine better than one?
Measles still kills half a million children each year. Many of these are young infants below the age of 9 months, which is the age at which vaccination is recommended. Previous studies have shown that the Edmonston-Zagreb (E-Z) vaccine is superior to other standard measles vaccines in evading neutralization by maternal antibody, which is the reason why measles vaccination is delayed to 9 months of age. We have conducted randomized immunogenicity and efficacy trials of two standard doses of E-Z vaccine given to infants at 4 and 9 months of age. The control groups were given a standard dose of E-Z vaccine at 9 months of age.
Immunogenicity studies
In a study performed in Sukuta, The Gambia we showed that the E-Z vaccine given at 4 months raised both antibody concentrations and cell mediated immunity, as judged by interferon gamma ELISpot counts following stimulation of peripheral blood mononuclear cells with measles peptides or measles virus. Two weeks after a booster dose of vaccine at 9 months of age antibody rose rapidly resulting in protective levels in all but two subjects. At 18 months of age cell mediated immunity, conferred mainly by CD4+ cells, was similar in the two groups. However, antibody concentrations were lower in the two dose group. In order to measure duration of immunity we are currently repeating these tests at 3 years of age before and after another boost with E-Z vaccine. We predict that both groups will respond similarly and quickly, suggesting protection following natural exposure.
The field trial
Our collaborators in Guinea Bissau have convincingly shown that the early dose of E-Z vaccine is very efficacious in protecting against measles and against death from measles in the 5 month period before the routine dose of vaccine at 9 months of age.
Children in this study will now be followed until 5 years of age to test whether protection and antibody persists similarly in the two groups. If this proves true the early two dose measles vaccine schedule can be recommended for routine use in countries where measles is endemic.
