Third Dose of Intramdermal H5N1 Vaccine Well-Tolerated but does Not Improve the Immune Response
Intradermal Flu Vaccine
Previous studies have suggested that lower dosages of seasonal flu vaccine given intradermally may work as well as higher dosages of the same vaccine given intramuscularly, enabling public health officials to "stretch" available doses of vaccine in a time of shortage. To test this principle with an H5N1 pandemic flu vaccine, NIAID initiated a vaccine trial to compare immune responses generated by an H5N1 vaccine given by the intradermal or the intramuscular route. The H5N1 vaccine formulations were produced for NIAID by sanofi pasteur.
Wendy Keitel, M.D., Shital M. Patel, M.D., and their Baylor College of Medicine colleagues conducted the trial. Results of their initial two-dose study among 100 participants indicated that antibody responses among volunteers given 3 or 9 micrograms of vaccine intradermally were similar to the antibody responses seen among volunteers given 15 micrograms intramuscularly: 4 percent, 5 percent, and 12 percent of volunteers, respectively, had a significant increase in antibody levels after two doses. Those given 45 micrograms by the intramuscular route, however, showed a significantly higher response rate: 56 percent of volunteers in this group responded.
In the current study, the Baylor team enrolled 77 healthy adults between the ages of 18 and 40 who had previously received two doses of the same vaccine one month apart and gave them a third dose of vaccine 6 months later to see if it boosted their antibody response. The participants, again divided into four groups, received either 3 or 9 micrograms intradermally or 15 or 45 micrograms intramuscularly. The dosages of vaccine were limited by the formulations available.
According to Dr. Patel, a quarter or less of the participants in the study groups given the vaccine intradermally or intramuscularly at 15 micrograms had a significant antibody response after the third dose, while nearly two-thirds of the volunteers in the group that received 45 micrograms intramuscularly had a similar response. For each dosage by either route of administration, the results show that giving a third dose of the vaccine 6 months later increased antibody titers to levels similar to those achieved after the first two doses.
"This small pilot study demonstrates that multiple doses of an inactivated H5N1 vaccine given by either the intradermal or the intramuscular route are safe and well tolerated," says Dr. Fauci. "It also provides a strong rationale for testing higher dosages of H5N1 vaccine given intradermally." Plans are under way to directly compare the immune responses generated by vaccinating either into the skin or into the muscle with an H5N1 vaccine containing higher levels of the same amount of antigen.