Several factors, including timing of vaccination, the interval between vaccines, immune response, and maternal antibody, influence vaccine efficacy.
The annual mortality rate in children who are less than five years old is 8.8 million world-wide; two-thirds of those children die from infectious disease. Notably, 3.6 million (41%) of those deaths occur in the neonatal period. "The diseases strike before we have the ability to vaccinate at a later age," said Kathryn M. Edwards, MD, Vanderbilt University School of Medicine, Nashville, TN, during the 48th annual meeting of the ISDA in Vancouver.
Consequently it is critical to try to ensure that the timing of vaccination and the intervals between vaccines provide optimal disease prevention. That said, there are obstacles to vaccination in infants, such as the occult or late diagnosis of congenital immunodeficiency with live vaccines in neonates. Increased risk of intussusception with gut inflammation is also a factor, as is an increased risk of wheezing.
Additionally, immunity in younger children is not as good as it is in older children. "Data from work done at Vanderbilt University in infants with rotavirus show that their antibodies lack the ability to make somatic mutations," Edwards said. There is also a cytokine (th2) bias in response to infection. "And we also know that maternal antibody plays an important role in suppressing immune responses in infants in terms of their ultimate response to vaccine," she said.
In addressing immune responses seen with early and delayed vaccination schedules, Edwards cited data on hepatitis B vaccination given in the neonatal period. "The vaccine has been effective in disease prevention," she said. "However, if we look at immunization schedules and corresponding immune responses, we see greater immune responses with the longer periods between the vaccines, allowing the B cells to mature somewhat. That said, good immune responses are mounted with the short-interval vaccine schedule, as well."
Neonatal influenza vaccine data on trivalent (TIV) vaccination administered at 2 and 3 months of age show good safety compared with placebo, with no difference in the rates of fever, tenderness, redness, and swelling between the two groups. However, while the immune responses were significantly better than placebo, they could have been better, Edwards said. "Geometric mean titres are about 1:32 for H1N1 and about 1:90 for H3N2, but if the correlate of protection would be an HAI of 1:40, that certainly isn't the highest immune response."
Edwards cited another study of infants who received TIV at 10 and 22 weeks, done at her institution. The results also showed good tolerability and immune responses, but like the earlier study, they could have been higher. Additionally, the study showed the impact of maternal antibody on immune responses in neonates. "If there was little maternal antibody, then the vaccine was quite immunogenic. In contrast, if the maternal antibody titre was greater than 1:8, only 12% of the children had a four-fold serologic increase. Very much the same thing was seen in HIN1." Edwards emphasized that even with the complicating factors that affect immune response in neonates, vaccination should be pursued given the early onset of many diseases.