Abstract
Three-hundred and eight outpatient elderly subjects (≥ 65 years) were randomly assigned to receive the MF59-adjuvanted influenza vaccine (FLUAD; n = 204) or a conventional subunit influenza vaccine (AGRIPPAL S1; n = 104) in order to compare the safety and immunogenicity of the two vaccines. Although mild pain at the injection site was reported more frequently by subjects immunised with the adjuvanted vaccine, both vaccines were shown to be safe and well tolerated. The adjuvanted vaccine was more immunogenic as indicated by higher post-immunisation geometric mean titres (GMTs) and by higher proportions of subjects with post-immunisation ≥ four fold increases of antibody titres or subjects with ≥ 1/160 post-immunisation HI titres. These differences, statistically significant for all three strains after immunisation, indicated that, by addition of the MF59 adjuvant emulsion, conventional subunit influenza antigens acquire an enhanced immunogenicity without any clinically significant increase of their reactogenicity.
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Barker WH, Mullooly JP. Influenza vaccination of elderly persons: Reduction in pneumonia and influenza hospitalizations and deaths. JAMA 1980; 244(22): 2547–2549.
Barker WH. Excess pneumonia and influenza associated hospitalization during influenza epidemics in the United States, 1970–78. AJPH 1986; 76: 761–765.
Glezen WP, Six HR, Frank AL, et al. Impact of epidemics upon communities and families. In: Kendal AP, Patriarca PA (eds), Options for the Control of Influenza II, New York: Alan R. Liss, Inc., 1986: 63–73.
Sprengel MJW, Beyer WEP, Kempen BM, et al. Risk factors for Influenza mortality? In: Hannoun C, Kendal AP, Klenk HD, Ruben FL (eds), Options for the Control of Influenza II, New York: Exerpta Medica, 1993: 15–23.
Sullivan KM. Health impact of influenza in the United States. Pharmacoeconomics 1996; (Suppl 3): 26–33; discussion 50–53.
Alling DW, Blackwelder WC, Stuart-Harris ChH. A study of excess mortality during influenza epidemics in the United States, 1968–1976. Am J Epidemiol 1981; 113(1): 30–43.
Hall WN, Goodman RA, Noble GR, et al. An outbreak of influenza B in an elderly population. J Infect Dis 1981; 144(4): 297–302.
Reece SM. Preventing influenza and its complications: A public health initiative for the year 2000. Nurse Pract 1995; 20(9): 32–36, 44.
Ahmed AE, Nicholson KG, Nguyen-Van-Tam JS. Reduction in mortality associated with influenza vaccine during 1989–90 epidemic. Lancet 1995; 346(8975): 591–595.
Wijma G, Ligthart GJ. Influenza vaccination for all elderly. Gerontol 1996; 42(5): 270–273.
Ikematsu H, Kashiwagi S. Efficacy and adverse reactions of influenza vaccine in the elderly. Nippon Rinsho 1997; 55(10): 2751–2157.
Nichol KL, Margolis KL, Wouremma J, et al. Effectiveness of influenza vaccine in the elderly. Gerontol 1996; 42(5): 274–279.
Mullooly JP, Bennet MD, Hornbrook MC, et al. Influenza vaccination programs for elderly persons: Cost-effectiveness in a health maintenance organization. Ann Intern Med 1994; 121(12): 947–952.
Fedson DS, Wadja A, Nicol JP, et al. Clinical effectiveness of influenza vaccination in Manitoba. JAMA 1993; 270(16): 1956–1961.
Van Hoecke C, Prikazsky V, Uto I, et al. Immunogenicity of an inactivated split influenza vaccine in institutionalized elderly patients. Gerontol 1996; 42(4): 190–198.
Patriarca PA, Weber JA, Parker RA, et al. Efficacy of Influenza vaccine in nursing homes: Reduction in illness and complications during an influenza A(H3N2) epidemic. JAMA 1985; 253(8): 1136–1139.
Strassburg MA, Greenland S, Sorvillo FJ, et al. Influenza in the elderly: Report of an outbreak and a review of vaccine effectiveness reports. Vaccine 1986; 4(1): 38–44.
Tannock GA. Alternatives in the control of influenza. Med J Aust 1991; 154(10): 692–695.
Giglio E, Roggi L, Bonanni P, et al. Influenza vaccination in subjects of the local health unit Arezzo (Tuscany-Italy) during the winter 1990/91. J Prev Med Hyg 1994; 35(3/4): 125–130.
Glathe H, Lange W. Influenza vaccination in older patients. Immunogenicity, epidemiology and available agents. Drugs Aging 1995; 6(5): 368–387.
Monto AS. The clinical efficacy of influenza vaccination. Pharmacoeconomics. 1996; 9(Suppl 3): 16–22; discussion 23–25.
Palache B. Influenza Vaccination — The effect of dose and age on the antibody response — A methodological evaluation of serological vaccination studies. Woensdag, 27 November 1991, OM 15.45 UUR.
Palache AM. Dose-comparative serological studies: Critical evaluation of the parameters to assess the antibody response to Influenza vaccination. In: Palache AM (ed), Influenza Vaccination. The Effect of Dose and Age on the Antibody Response, Amsterdam, Netherlands: Broos Amsterdam BV, 1991; Chap. 4: 83–119.
Tamura A, Nasal Cholera Toxin-B combined Influenza Vaccine. Abstract book — International Scientific Conference on “Options for the control of Influenza” II — Courchevel, France — 26 Sep.–2 Oct. 1992; 54.
Katz J. Evaluation of heat labile enterotoxin (LT) from Escherichia coli as an adjuvant for oral immunization with inactivated Influenza virus vaccine. Abstract book — International Scientific Conference on “Options for the control of Influenza” II — Courchevel, France — 26 Sep.–2 Oct. 1992; 56.
Nerome K, Yoshioka Y, Ishida M, et al. Development of a new type of influenza subunit vaccine made by muramyldipeptide-liposome: Enhancement of humoral and cellular immune responses. Vaccine 1990; 8(5): 503–509.
Wilschut J, De Haan A, Geerligs HJ, et al. “Liposomal vaccines and mucosal immunity” Abstract book — International Scientific Conference on “Options for the control of Influenza” II — Courchevel, France — 26 Sep.–2 Oct. 1992; 56.
Provinciali M, Di Stefano G, Colombo M, et al. Adjuvant effect of low-dose interleukin-2 on antibody response to influenza virus vaccination in healthy elderly subjects. Mech Ageing Dev 1994; 77(2): 75–82.
McElhancy JE, Meneilly GS, Pinkoski MJ, et al. Vaccine-related determinants of the interleukin-2 response to influenza vaccination in healthy young and elderly adults. Vaccine 1995; 13(1): 6–10.
Hsia J, Tang T, Parrott M, et al. Augmentation of the immune response to influenza vaccine by acetylsalicylic acid: A clinical trial in a geriatric population. Meth Find Exp Clin Pharmacol 1994; 16(9): 677–683.
Biselli R, Fagiolo U, Nisini R, et al. Humoral response to influenza hemagglutinin: Oligoclonal spectrotype and failure of thymopentin as immunoadjuvant. Gerontol 1995; 41(1): 3–10.
Degelau J, Guay D, Hallgren H. The effect of DHEAS on influenza vaccination in ageing adults. J Am Geriatr Soc 1997; 45(6): 747–751.
Powell MF, Newman MJ. Vaccine design: The subunit and adjuvant approach. New York: Plenum Publishing Corporation, 1995: 277–295.
Ott G, Barchfeld GL, Chernoff D, et al. MF59. Design and evaluation of a safe and potent adjuvant for human vaccines. Pharm Biotechnol 1995; 6: 277–296.
Gupta RK, Siber GR. Adjuvants for human vaccines-current status, problems and future prospects. Vaccine 1995; 13(14): 1263–1276.
Higgins DA, Carlson JR, Van Nest G. MF59 adjuvant enhances the immunogenicity of influenza vaccine in both young and old mice. Vaccine 1996; 14(6): 478–484.
Martin JT. Development of an adjuvant to enhance the immune response to influenza vaccine in the elderly. Biologicals 1997; 25(2): 209–213.
Minutello M, Senatore F, Cecchinelli G, et al. Safety and immunogenicity of an inactivated subunit influenza virus vaccine combined with MF59 adjuvant emulsion in elderly subjects, immunized for three consecutive influenza seasons. Vaccine 1999; 17(2): 99–104.
De Donato S, Granoff D, Minutello M, et al. Safety and immunogenicity of MF59-adjuvanted influenza vaccine in the elderly. Vaccine 1999; 17 (23, 24): 3094–3101.
Menegon T, Baldo V, Bonello C, et al. Influenza vaccines: Antibody responses to split virus and MF59-adjuvanted subunit virus in an adult population. Eur J Epidemiol 1999; 15(6): 573–576.
WHO. Recommended composition of influenza virus vaccines for use in the 1994–1995 season. Wkly Epidemiol Rec 1994; 69(8): 53–56.
Dowdle WA, Kendal AP, Noble GR. Influenza viruses. In: Lennette E, Schmidt N (eds), Diagnostic Procedures for Viral, Rickettsial and Chlamydial Infection. 5th ed. Washington: American Public Health Association Inc. 1979: 603–605.
Carrat F, Valleron AJ. Influenza mortality among the elderly in France, 1980–90: How many deaths may have been avoided through vaccination? J Epidemiol Commun Health 1995; 49(4): 419–425.
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Gasparini, R., pozzi, T., Montomoli, E. et al. Increased immunogenicity of the MF59-adjuvanted influenza vaccine compared to a conventional subunit vaccine in elderly subjects. Eur J Epidemiol 17, 135–140 (2001). https://doi.org/10.1023/A:1017919305501
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DOI: https://doi.org/10.1023/A:1017919305501