Safety and immunogenicity of a high dosage trivalent influenza vaccine among elderly subjects

Baylor College of Medicine, One Baylor Plaza, MS: BCM280, Houston, TX 77030, United States.
Vaccine (Impact Factor: 3.62). 12/2007; 25(44):7656-63. DOI: 10.1016/j.vaccine.2007.08.042
Source: PubMed


To improve immune responses to influenza vaccine, a trivalent inactivated vaccine containing 60 microg of the HA of each component (A/H3N2, A/H1N1, B) was compared to a licensed vaccine containing 15 microg of the HA of each. More local and systemic reactions were reported by subjects given the high dosage but only local pain and myalgias were significantly increased. The high dosage vaccine induced a higher frequency of serum antibody increases (> or =4-fold) in both hemagglutination-inhibiting (HAI) and neutralization tests for all three vaccine viruses in the total group as well as subjects vaccinated and those not vaccinated the previous year. Mean titers of antibody attained, the magnitude of antibody increases and the frequencies of persons with final HAI antibody titers > or =1:32, > or =1:64, and > or =1:128 were all greater for the high dosage group in both serologic tests, for all groups, and for all vaccine viruses. These increased immune responses should provide increased protection against influenza in the elderly.

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Available from: Wilbur H Chen
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    • "No clinically relevant differences in reactions or AEs were detected between the ID and IM vaccines, and there were no obvious safety concerns for any of the vaccines. As expected and as described in previous studies [18] [25] [26], solicited injection-site and systemic reactions were more common in older adults receiving HD vaccine than in those receiving SD vaccine . Nevertheless, most of these reactions were self-limited and of short duration. "
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    ABSTRACT: We conducted a randomized, controlled, multicenter, phase II study to evaluate the immunogenicity and safety of an investigational intradermal (ID) trivalent influenza vaccine (TIV) and a high-dose (HD) intramuscular (IM) TIV in older adults (≥65 years of age). Older adult subjects were immunized with ID vaccine containing either 15μg hemagglutinin (HA)/strain (n=636) or 21μg HA/strain (n=634), with HD IM vaccine containing 60μg HA/strain (n=320), or with standard-dose (SD) IM vaccine (Fluzone(®); 15μg HA/strain; n=319). For comparison, younger adults (18-49 years of age) were immunized with SD IM vaccine. In older adults, post-vaccination geometric mean titers induced by the ID vaccines were superior to those induced by the SD IM vaccine for the A/H1N1 and A/H3N2 strains and non-inferior for the B strain. Seroconversion rates induced by the ID vaccines were superior to those induced by the SD IM vaccine in older adults for the A/H1N1 and B strains and non-inferior for the A/H3N2 strain. Results did not differ significantly for the two ID vaccine dosages. Post-vaccination geometric mean titers, seroconversion rates, and most seroprotection rates were significantly higher in HD vaccine recipients than in older adult recipients of the SD IM or ID vaccines and, for most measures, were comparable to those of younger adult SD IM vaccine recipients. Injection-site reactions, but not systemic reactions or unsolicited adverse events, were more common with the ID vaccines than with the IM vaccines. No treatment-related serious adverse events were reported. This study demonstrated that: (1) the ID and HD vaccines were well-tolerated and more immunogenic than the SD IM vaccine in older adults; (2) the HD vaccine was more immunogenic than the ID vaccines in older adults; and (3) the HD vaccine in older adults and the SD IM vaccine in younger adults elicited comparable antibody responses ( identifier no.: NCT00551031).
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    • "Currently, the relative efficacy of the high-dose formulation versus the standard dose is unknown, with a 3-year post-licensure study due for completion in 2012 [42]. However, initial studies examining immunogenicity show a clear advantage for higher doses in the elderly [45] [46] [47]. In one double-blinded placebo controlled study carried out in persons ≥65 years of age, the high dose formulation gave both higher seroconversion rates, as well as increasing antibody titers up to 80% when compared to the standard dose [45]. "
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    • "A variety of factors impact the heterogeneity and inter-individual variations in vaccine-induced immune responses. These include factors such as gender [10], age [11], ethnicity [12], vaccine dose [13], vaccine storage/cold chain [14], immune system function/integrity [15], size (body mass index [BMI]) [16], smoking [17], and others. Logically, genetics play an important—and defining—role in vaccine response. "
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