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: 3.49). 12/2007; 25(44):7656-63. DOI: 10.1016/j.vaccine.2007.08.042
Source: PubMed

ABSTRACT 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, Aug 21, 2015
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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).
    Vaccine 10/2013; 32(21). DOI:10.1016/j.vaccine.2013.09.074 · 3.49 Impact Factor
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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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    ABSTRACT: With advances in global health care, ageing populations are expected to grow worldwide throughout the 21(st) century. Increased lifespan is a testament to modern medical and social practices, but also presents a growing challenge to a system with limited resources. Elderly populations present specific concerns related to preventative health practices, especially vaccination. Although the power of vaccination is unquestionable in controlling infectious disease, immunosenescence can lead to reduced immune responses following immunization in the elderly, and increased morbidity and mortality. Further complicating this issue, some vaccines themselves may pose a substantial safety risk in the elderly when compared to younger counterparts. Though any health care intervention must balance risk and reward, safety and immunogenicity are often poorly characterized in older populations. This review explores several domestic and travel vaccines, examining what is known concerning efficacy and safety in the elderly, and considers future alternatives.
    Open Longevity Science (Formerly The Open Aging Journal ) 06/2012; 6(2012):64-72. DOI:10.2174/1876326X01206010064
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    • "The current large multi-center study had sufficient power to reveal improvements in protective seroresponses to influenza vaccination among residents in longterm care facilities. Previous studies usually included smaller sample sizes of dissimilar subgroups (young, ambulatory elderly, residents of long-term care facilities with the exclusion of demented patients), and therefore type II errors may explain the divergence of results concerning the effects of high dose influenza vaccines [Arden et al., 1986; Gross et al., 1988; Peters et al., 1988; Sullivan et al., 1990; Remarque et al., 1993, 1999; Palache et al., 1993a,b; Keitel et al., 2006; Couch et al., 2007]. In this randomized trial, differences between the vaccination strategies were measured indirectly instead of by a direct test of efficacy. "
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    ABSTRACT: Increased vaccine doses and mid-season boosting may increase the proportion of residents with protective immunity from influenza in long-term care facilities. In a multi-center study (1997-1998), 815 residents from 14 long-term care facilities were assigned at random to receive 15 or 30 microg of inactivated influenza vaccine, followed by a 15 microg booster vaccine or a placebo vaccine at Day 84. Seroresponses were re-analyzed by hemagglutination-inhibition (> or =4-fold titer increases, protective titer > or =40, geometric mean titers. Forty percent of the participants had pre-vaccination titers > or =40. At Day 25 after vaccination, this increased to 66.3% after a 15 microg dose versus 73.3% after a dose of 30 microg (P = 0.049). Participants receiving a 30 microg dose followed by a 15 microg booster showed more > or =4-fold titer increases at Day 109 (43.6% vs. 35.4%, P = 0.003) and protective titers > or =40 (74.2% vs. 64.6%, P = 0.041), compared to those receiving only a 15 microg dose. Differences were most apparent in participants with low pre-vaccination titers. Booster vaccination after an initial 15 microg dose of the vaccine did not increase the protective rate (61.9% vs. 63.9% after placebo). The number of participants needed to vaccinate to protect one additional resident by a dose of 15 microg was 4, by a dose of 30 microg 3, and 15 when using a 30 microg dose instead of 15 microg. Doubling the dose of influenza vaccine increased protection-related responses among residents of long-term care facilities, especially in those with low pre-vaccination titers.
    Journal of Medical Virology 05/2009; 81(5):908-14. DOI:10.1002/jmv.21456 · 2.22 Impact Factor
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