Two systematic reviews and meta-analyses published in The Lancet Infectious Diseases report a good immune response and protection when the measles vaccine is administered before 9 months of age, but not as good as when given later, and a first dose given before 9 months of age might affect how later doses perform.
Lower protection with earlier immunization
In the first meta-analysis, researchers from the Netherlands and the World Health Organization (WHO) looked at data from 56 studies on safety, immunogenicity, and efficacy/effectiveness of measles-containing vaccines (MCVs) administered to infants younger than 9 months. An initial dose (called MCV1) is currently recommended at 9 months of age in countries with ongoing measles transmission, and at 12 months in countries with low risk of measles, with a second dose administered at 4 to 6 years.
In infants who received a dose before 9 months, the vaccine was found to be safe and well-tolerated, according the pooled data. The pooled vaccine effectiveness of MCV1 in infants younger than 9 months against measles was 58% (95% confidence interval [CI], 9% to 80%). The pooled vaccine effectiveness estimate from within-study comparisons of infants younger than 9 months vaccinated with MCV1 was 51% (95% CI, −44% to 83%), and for those aged 9 months and older at vaccination, it was 83% (95% CI, 76% to 88%), the authors said.
The authors concluded, "A large proportion of infants receiving MCV1 before 9 months of age are protected and the vaccine is safe, although higher antibody titres and vaccine effectiveness are found when MCV1 is administered at older ages. Recommending MCV1 administration to infants younger than 9 months for those at high risk of measles is an important step towards reducing measles-related mortality and morbidity."
The results of this analysis were presented to the WHO in 2015, and they resulted in updated WHO recommendations on MCV administration at 6 months of age for infants at high risk of measles infection.
Possible effect on later doses
In the second analysis, the same group of researchers looked at the effect early vaccine dosing has on subsequent immune responses to the standard vaccine doses. In 13 studies, the pooled proportion of infants seropositive after two MCV doses, with MCV1 administered before 9 months of age, was 98% (95% CI, 96% to 99%)—not significantly different from seropositivity after a two-dose MCV schedule starting later (P = 0.087).
"We also found some evidence that MCV1 administered to infants younger than 9 months resulted in lower antibody titres after one or two subsequent doses of MCV than when measles vaccination is started at age 9 months or older," the authors said. "The clinical and public-health relevance of this immunity blunting effect are uncertain."
This uncertainty "suggests that an early dose might decrease long-term protection because further doses were associated with reduced antibody titres and avidity," write Nicola Principi, MD, and Susanna Esposito, MD, both with the University of Milan, in an accompanying commentary on the two studies.
"Compared with infants administered MCV at 9 months of age or later, seroconversion and antibody concentrations in those vaccinated before 9 months of age were significantly reduced. Vaccine effectiveness was 51% versus 83%, highlighting that a substantial proportion of infants younger than 9 months remained susceptible to measles, and that only further doses could ensure that all infants were protected," they said.
Ultimately, a three-dose vaccine schedule would be difficult and costly to implement, as the current two-dose schedule already sees poor adherences, Principi and Esposito conclude. A third dose of MCV administered in early infancy should be considered only in emergency situations, they add.
See also:
Sep 20 Lancet Infect Dis immunogenicity and effectiveness study
Sep 20 Lancet Infect Dis subsequent doses study
Sep 20 Lancet Infect Dis commentary
