Adjuvanted vaccines against influenza in the elderly

Abstract

Influenza is an important public health issue, especially with the aging of the population, since the most serious consequences of the illness affect the elderly. Between 1979 and 2001, approximately 41000 annual deaths have been attributed to influenza in the United States (Dushoff, 2005). Annual vaccination is a key strategy employed to combat this illness, and while it is very effective in healthy young adults, it is much less successful in the elderly. The impaired immune system with aging may contribute to this diminished ability of the vaccine to afford protection. Strategies to improve vaccine efficacy, particularly for the aged population, are necessary. One potential strategy is the inclusion of adjuvants in the vaccine formulations to enhance the immune response. Adjuvants have been shown to improve antibody production, allow dose-sparing, and potentially increase cross-reactivity. These benefits are important in combating both seasonal influenza and pandemic influenza, as current seasonal vaccine effectiveness depends on close matching to the circulating virus, and fast production of pandemic vaccines are key to their effectiveness. While much is still unknown about adjuvants, especially their mechanisms of action, their potential at improving the efficacy of influenza vaccines has been well recognized, particularly in the elderly.

Key words： influenza vaccine; elderly; adjuvant

Acknowledgments

We thank Jack Ju for his assistance in preparing this manuscript.

References

1 Andrews N, Waight P, Yung C F, Miller E (2011). Age-specific effectiveness of an oil-in-water adjuvanted pandemic (H1N1) 2009 vaccine against confirmed infection in high risk groups in England. J Infect Dis, 203(1): 32–39

PMID

2 Banzhoff A, Gasparini R, Laghi-Pasini F, Staniscia T, Durando P, Montomoli E, Capecchi P L, di Giovanni P, Sticchi L, Gentile C, Hilbert A, Brauer V, Tilman S, Podda A (2009). MF59-adjuvanted H5N1 vaccine induces immunologic memory and heterotypic antibody responses in non-elderly and elderly adults. PLoS ONE, 4(2): e4384

PMID

3 Beigel J H, Voell J, Huang C Y, Burbelo P D, Lane H C (2009). Safety and immunogenicity of multiple and higher doses of an inactivated influenza A/H5N1 vaccine. J Infect Dis, 200(4): 501–508

PMID

4 Bernstein E, Kaye D, Abrutyn E, Gross P, Dorfman M, Murasko D M (1999). Immune response to influenza vaccination in a large healthy elderly population. Vaccine, 17(1): 82–94

PMID

5 Camilloni B, Neri M, Lepri E, Basileo M, Sigismondi N, Puzelli S, Donatelli I, Iorio A M (2010). An influenza B outbreak during the 2007/2008 winter among appropriately immunized elderly people living in a nursing home. Vaccine, 28(47): 7536–7541

PMID

6 Chan T C, Hung I F, Luk J K, Shea Y F, Chan F H, Woo P C, Chu L W (2011). Efficacy of dual vaccination of pandemic H1N1 2009 influenza and seasonal influenza on institutionalized elderly: a one-year prospective cohort study. Vaccine, 29(44): 7773–7778

PMID

7 Cheong H J, Song J Y, Heo J Y, Noh J Y, Choi W S, Park D W, Wie S H, Kim W J (2011). Immunogenicity and safety of the influenza A/H1N1 2009 inactivated split-virus vaccine in young and older adults: MF59-adjuvanted vaccine versus nonadjuvanted vaccine. Clin Vaccine Immunol, 18(8): 1358–1364

PMID

8 de Bruijn I A, Nauta J, Gerez L, Palache A M (2006). The virosomal influenza vaccine Invivac: immunogenicity and tolerability compared to an adjuvanted influenza vaccine (Fluad in elderly subjects. Vaccine, 24(44-46): 6629–6631

PMID

9 Deans G D, Stiver H G, McElhaney J E (2010). Influenza vaccines provide diminished protection but are cost-saving in older adults. J Intern Med, 267(2): 220–227

PMID

10 Dushoff J (2005). Assessing influenza-related mortality: comment on Zucs et al. Emerg Themes Epidemiol, 2(1): 7

PMID

11 Fragapane E, Gasparini R, Schioppa F, Laghi-Pasini F, Montomoli E, Banzhoff A (2010). A heterologous MF59-adjuvanted H5N1 prepandemic influenza booster vaccine induces a robust, cross-reactive immune response in adults and the elderly. Clin Vaccine Immunol, 17(11): 1817–1819

PMID

12 Gasparini R, Schioppa F, Lattanzi M, Barone M, Casula D, Pellegrini M, Veitch K, Gaitatzis N (2010). Impact of prior or concomitant seasonal influenza vaccination on MF59-adjuvanted H1N1v vaccine (Focetria) in adult and elderly subjects. Int J Clin Pract, 64(4): 432–438

PMID

13 Govaert T M, Thijs C T, Masurel N, Sprenger M J, Dinant G J, Knottnerus J A (1994). The efficacy of influenza vaccination in elderly individuals. A randomized double-blind placebo-controlled trial. JAMA, 272(21): 1661–1665

PMID

14 Khurana S, Verma N, Yewdell J W, Hilbert A K, Castellino F, Lattanzi M, Del Giudice G, Rappuoli R, Golding H (2011). MF59 adjuvant enhances diversity and affinity of antibody-mediated immune response to pandemic influenza vaccines. Sci Transl Med, 3(85): 85ra48

PMID

15 Langley J M, Risi G, Caldwell M, Gilderman L, Berwald B, Fogarty C, Poling T, Riff D, Baron M, Frenette L, Sheldon E, Collins H, Shepard M, Dionne M, Brune D, Ferguson L, Vaughn D, Li P, Fries L (2011). Dose-sparing H5N1 A/Indonesia/05/2005 pre-pandemic influenza vaccine in adults and elderly adults: a phase III, placebo-controlled, randomized study. J Infect Dis, 203(12): 1729–1738

PMID

16 Lee B Y, Ercius A K, Smith K J (2009). A predictive model of the economic effects of an influenza vaccine adjuvant for the older adult (age 65 and over) population. Vaccine, 27(16): 2251–2257

PMID

17 Madhun A S, Akselsen P E, Sjursen H, Pedersen G, Svindland S, Nøstbakken J K, Nilsen M, Mohn K, Jul-Larsen A, Smith I, Major D, Wood J, Cox R J (2010). An adjuvanted pandemic influenza H1N1 vaccine provides early and long term protection in health care workers. Vaccine, 29(2): 266–273

PMID

18 McElhaney J E, Dutz J P (2008). Better influenza vaccines for older people: what will it take? J Infect Dis, 198(5): 632–634

PMID

19 McElhaney J E, Effros R B (2009). Immunosenescence: what does it mean to health outcomes in older adults? Curr Opin Immunol, 21(4): 418–424

PMID

20 McKee A S, MacLeod M K, Kappler J W, Marrack P (2010). Immune mechanisms of protection: can adjuvants rise to the challenge? BMC Biol, 8(1): 37

PMID

21 McKee A S, Munks M W, Marrack P (2007). How do adjuvants work? Important considerations for new generation adjuvants. Immunity, 27(5): 687–690

PMID

22 Neafsey P J, Tyler C (2005). Efficacy of influenza vaccine in the elderly. Home Healthc Nurse, 23(10): 640–641

PMID

23 O’Hagan D T, Rappuoli R, De Gregorio E, Tsai T, Del Giudice G (2011). MF59 adjuvant: the best insurance against influenza strain diversity. Expert Rev Vaccines, 10(4): 447–462

PMID

24 Phillips C J, Matyas G R, Hansen C J, Alving C R, Smith T C, Ryan M A (2009). Antibodies to squalene in US Navy Persian Gulf War veterans with chronic multisymptom illness. Vaccine, 27(29): 3921–3926

PMID

25 Podda A (2001). The adjuvanted influenza vaccines with novel adjuvants: experience with the MF59-adjuvanted vaccine. Vaccine, 19(17-19): 2673–2680

PMID

26 Puig-Barberà J, Diez-Domingo J, Pérez Hoyos S, Belenguer Varea A, González Vidal D (2004). Effectiveness of the MF59-adjuvanted influenza vaccine in preventing emergency admissions for pneumonia in the elderly over 64 years of age. Vaccine, 23(3): 283–289

PMID

27 Roman F, Vaman T, Kafeja F, Hanon E, Van Damme P (2010). AS03(A)-Adjuvanted influenza A (H1N1) 2009 vaccine for adults up to 85 years of age. Clin Infect Dis, 51(6): 668–677

PMID

28 Ruf B R, Colberg K, Frick M, Preusche A (2004). Open, randomized study to compare the immunogenicity and reactogenicity of an influenza split vaccine with an MF59-adjuvanted subunit vaccine and a virosome-based subunit vaccine in elderly. Infection, 32(4): 191–198

PMID

29 Thompson W W, Moore M R, Weintraub E, Cheng P Y, Jin X, Bridges C B, Bresee J S, Shay D K (2009). Estimating influenza-associated deaths in the United States. Am J Public Health, 99(S2 Suppl 2): S225–S230

PMID

30 Treanor J J, Campbell J D, Zangwill K M, Rowe T, Wolff M (2006). Safety and immunogenicity of an inactivated subvirion influenza A (H5N1) vaccine. N Engl J Med, 354(13): 1343–1351

PMID

31 Vajo Z (2011). The seasonal influenza vaccine Agriflu(®). Expert Rev Vaccines, 10(11): 1513–1517

PMID

32 Vesikari T, Groth N, Karvonen A, Borkowski A, Pellegrini M (2009). MF59-adjuvanted influenza vaccine (FLUAD) in children: safety and immunogenicity following a second year seasonal vaccination. Vaccine, 27(45): 6291–6295

PMID