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

Abstract

To improve immune responses to influenza vaccine, a trivalent inactivated vaccine containing 60 µg of the HA of each component (A/H3N2, A/H1N1, B) was compared to a licensed vaccine containing 15 µg 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 (≥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 ≥1:32, ≥1:64, and ≥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. KeywordsInfluenza; vaccines; elderly IntroductionTrivalent inactivated influenza vaccines (TIV) are effective for prevention of influenza and its complications among the elderly. However, there is a need to improve these vaccines because the degree of protection is variable and sometimes low [1,2]. One option for improving TIV is to increase vaccine dosage so as to increase serum antibody responses to the hemagglutinin (HA) as measured in hemagglutination-inhibiting (HAI) and neutralization (neut) tests. Increasing antibody to the HA in serum correlates with increasing protection against infection and illness after exposure to influenza and available information indicates that this antibody is the primary mediator of immunity to infection [3,5].A number of studies have shown that increasing the dosage of TIV will induce an increase in the serum antibody response [6][7][8][9][10][11][12][13][14][15][16][17][18]. Dosages as high as 135 µg of each HA in TIV (containing an A/H3N2, A/H1N1 and B virus strain) have been shown to be safe in elderly subjects and to induce significantly greater serum antibody responses as dosage was increased [15,17]. In a recent study, we tested the 2000-2001 formulation of licensed trivalent vaccine containing the standard 15 µg of the HA of each component as well as unlicensed concentrations of the same vaccine containing 30 ug and 60 ug of each HA; the increased dosage was well tolerated and induced an increased antibody response [16]. To confirm this finding and to evaluate a high dosage vaccine designed for clinical development, a larger number of elderly subjects were given a new 60 µg per HA TIV. The gelatin and thimerosal components in licensed vaccine were removed and only the three viral components used in [2004][2005] Materials and Methods Study DesignThis was a multi-site, phase II, randomized, double-blind, stratified study. The primary hypothesis was that the new TIV containing 60 µg of each antigen would be well tolerated and induce a significantly greater serum HAI ...

Sex differences in injection site reactions with human vaccines

“…Inactivated, split trivalent Prospective, randomized, double-blind study with high dose Injection site pain, influenza vaccine and standard dose vaccine, n = 414; 212 M, 202 F, F > M. Couch et al 56 Age range 65-95 yrs. 59 …”

A dose-ranging study in older adults to compare the safety and immunogenicity profiles of MF59®-adjuvanted and non-adjuvanted seasonal influenza vaccines following intradermal and intramuscular administration

“…Strategies to optimize responses to vaccination in older adults include the use of adjuvants, 8,36 higher antigen doses, 11,12 ID delivery, 14,25,33,34,37 and addition of a second B strain (quadrivalent influenza vaccine, QIV). Here we report the findings of a study which compared the immunogenicity and safety profiles of low-dose non-adjuvanted ID TIV (containing either 6 µg or 12 µg of A/H3N2 antigen), full-dose non-adjuvanted IM TIV, and full-dose MF59-adjuvanted IM TIV (both IM groups containing either 15 µg or 30 µg of A/H3N2 antigen).…”

“…Overall, while MF59 adjuvantation increased pain at the site of injection, and intradermal delivery increased unsolicited adverse events, erythema, induration, and swelling at the injection site, both strategies of vaccination strongly enhanced the immunogenicity of seasonal influenza vaccine in older adults compared with conventional non-adjuvanted intramuscular delivery. adjuvanted trivalent influenza vaccines (aTIVs), [8][9][10] increasing the dose of antigens, [11][12][13] , intradermal (ID) vaccine delivery, 14,15 and virosomal subunit vaccines. 16 …”

Practical review of immunizations in adult patients with cancer

“…24 The authors also reported no difference in adverse reactions between the regular-dose and high-dose groups, 24 although others have reported that the high-dose vaccine is associated with increased local pain and myalgia. 25 The second novel method of delivering the influenza vaccine is the 2-shot influenza vaccine. Lo et al found that the vaccine response rate of patients who received 2 doses (71%) was significantly higher than that of patients who received one dose (42%; p D 0.006).…”