Should young children be vaccinated against influenza? How can the efficacy of a new influenza vaccine (a new vaccine must be formulated every year) be assessed for indication in young children?

On June 10, Dr. Steven Black, professor of pediatrics, Cincinnati Children's Hospital, Ohio, U.S., presented an analysis of clinical trial results on new influenza vaccines published in recent years1, which brought key evidence to answer these questions. The study which he spoke about at the 29th annual meeting of the European Society for Paediatrics Infectious Diseases (ESPID), in The Hague, demonstrated that: the standard measurement of protection for influenza vaccination may not be applicable for young children; and there is a need for pediatric influenza recommendations based on appropriate correlates of protection.


A Public Health Concern

Two reasons make pediatric influenza a major concern. First, influenza has a high morbidity rate in children. While the burden of pediatric influenza is currently under evaluation in Europe, the first results of the European Paediatric Influenza Analysis (EPIA) project show that during flu season, between 0.4 percent and 18 percent of children consult a physician for influenza-like illnesses, the majority of which are influenza2.

Second, children are identified as a major reservoir from which the virus can disseminate to the general population and, especially, to the number-one high-risk group, the elderly.

Unfortunately, until recently, influenza vaccines proved to have a lesser efficacy in young children than in adults, and the view was often taken that it was useless to vaccinate them. However, the potential availability of a new generation of adjuvanted vaccines for children has recently brought hope. Dr. Black cited a two-year clinical trial conducted in Germany and Finland by Timo Vesikari and Markus Knuf, which showed that the Fluad adjuvanted influenza vaccine protected 86 percent of children aged 6 months to 6 years, while a nonadjuvanted vaccine protected only 43 percent1.


Antibody Levels as Predictors

Working on the data collected during the above-mentioned trial, Dr. Black went further and looked for children’s correlates of protection. Correlates of protection are biological measurements, in this case antibody levels, associated with protection against a disease. His results offer both an explanation for the better protection offered by the adjuvanted vaccine and a means to predict the efficacy of newly developed vaccines in young children.

The key factor is the antibody levels induced by the vaccines, measured in titers. “In 1972, it was established that a titer of 1:40 had a correlate of protection of 50 percent of vaccinated people,” said Dr. Black. “This titer has been used as a criterion to register the influenza vaccine, even though 50 percent was not that high of a protection. I showed that this level of antibody is far from having the same efficacy in children as in adults.” The data presented by Dr. Black demonstrated that children between 6 months and 6 years old need an antibody titer almost three times greater (1:110) to benefit from the same protection as adults.

“The higher efficacy of adjuvanted vaccines is associated with the higher levels of antibodies they induce,” Dr. Black explained. The study showed that a nonadjuvanted vaccine induced antibody titers higher than 1:40 in 65.2 percent of vaccinated children and had a clinical efficacy of 45 percent, while these figures were, respectively, 98.7 percent and 89 percent with an adjuvanted vaccine.

Practices Must Change

“These results show standard measurement of protection for influenza vaccination in adults is not suitable for young children whose immune systems are still maturing and therefore need more help to fight off infections,” said Dr. Black. “This calls for a rethink of how we protect against these infections in the first years of life and ultimately pediatric influenza vaccination recommendations based on appropriate correlates of protection.”