Is It More Effective to Delay MMR Vaccination?

Recently, I asked the question is it safer to delay MMR vaccination?  Many of those who are opposed to the current schedule of vaccinations or have heard anti-vaccine claims and fear that vaccines somehow overwhelm an infant's immune system may put off getting their children immunized until well after the age recommended by the CDC and AAP. This decision not only leaves a child at risk of infection for a longer period, but, as I discussed in that post, new research on the MMR vaccine indicates that there is an increased risk of seizures and fever associated with delaying that vaccine. So delaying might not necessarily be safer, at least in terms of adverse reactions to the MMR vaccine. The authors of the recent paper speculated that one probable cause of this increased risk is due to a more robust immune reaction the older a child is when they receive their first dose of measles-containing vaccine.

Another recent study, Measles in Children Vaccinated With 2 Doses of MMR, by F. Defay, G. De Serres, D. M. Skowronski, N. Boulianne, M. Ouakki, M. Landry, N. Brousseau, and B. J. Ward and published online on October 21, 2013 in Pediatrics, asked a related question: does delaying the first dose of measles vaccine improve efficacy? Well, really, the question they asked was, "does age of first MMR vaccination affect vaccine efficacy in children who received 2 doses", but my paraphrase is close enough.

Back in 2011, a measles outbreak hit Quebec, Canada. The disease affected 776 individuals; 725 confirmed by lab testing and the remainder fitting the clinical case definition. It began after a high school employee (full study behind paywall) acquired the infection either in the Caribbean or at an airport in Montreal on his return to Canada. He had received 1 dose of measles vaccine in childhood, though at what age is unknown. Of the 725 confirmed cases, 86 (12%) were hospitalized, with most of those in children, including 4 infants. The majority of the cases (79%) were either unvaccinated or had unknown vaccination status. The remainder had received either one or two doses of vaccine and generally had milder illness. This raised a question: why were people who received two doses of vaccine getting infected?

Enter the new study. The authors set out to find a possible reason that those who had received two doses of the MMR still got sick. In particular, did the age when the first dose was administered have an effect on the effectiveness of the vaccine? There was a previous study involving 41 cases that found a statistically significant effect of age on efficacy. But because that study was so small, a larger study was needed to see if the results could be generalized to a larger population. Defay et al. looked at 102 cases and 510 controls, matched for date of birth (within 6 months) and school attended. Controls were drawn randomly from the provincial measles vaccination registry from all students meeting the matching criteria. All cases and controls had received two doses of MMR-II, produced by Merck.

Those who were immunized at 12-13 months of age were found to have a 5-fold greater risk of getting measles than those who got the MMR at 15 months of age or later. One possible explanation for this is the persistence of maternal antibodies against measles. Maternal antibodies can attack the vaccine-strain virus, rendering the vaccine less effective. The lowered efficacy in subjects immunized at 12-14 month old was more noticeable in those children who were born to mothers who had immunity from infection instead of vaccination. The results of this study could have implications for the Canadian vaccination schedule, since most provinces only recommend the MMR at 12 months.

Authorities should carefully weigh, however, whether or not to change the recommended vaccination age from 12 months for the first dose to 15 months (or even 12-15 months). As I mentioned recently, we've known for at least 40 years that the MMR vaccine is less effective if given before 12 months of age, and studies in the U.S. in the 1970s found, similar to the current Defay study, that MMR was less effective if the first dose was given at 12-14 months than at 15+ months of age. This resulted in the U.S. raising the recommended age of measles immunization to 15 months, possibly causing some unintended consequences:

Unfortunately, this change may have contributed to the epidemic of 1989 to 1991 by leaving the group of 12- to 14-month-old children unprotected; in 1990, it contributed 2,551 cases, or >11% of the cases in the epidemic (all cases, all ages) (24). More importantly,the delay in immunization from 12 to 15 months probably resulted in fewer preschool children receiving measles vaccine and resulted in a larger number of susceptible children in this age group who subsequently acquired measles.

So is the MMR vaccine more effective if we delay vaccination until 15 months of age? The results of Defay et al. add to the body of evidence suggesting that the vaccine is more effective if we delay until 15 months of age. On the other hand, delaying vaccination may increase the risk of febrile seizures and leave children vulnerable to infection for a longer period of time. It is a difficult and complex decision to make, and it plays a role not only in preventing the resurgence of measles in regions that have eliminated the virus from sustained, endemic transmission, such as in the Americas, but can also have a significant impact on global measles eradication efforts.