Abstract
Isolation of the causative virus of influenza in 1933, followed by the discovery of embryonated hen eggs as a substrate, quickly led to the formulation of vaccines. Virus-containing allantoic fluid was inactivated with formalin. The phenomenon of antigenic drift of the virus HA was soon recognized and, as WHO began to coordinate the world influenza surveillance, it became easier for manufacturers to select an up-to-date virus. Influenza vaccines remain unique in that the virus strain composition is reviewed yearly but modern attempts are being made to free manufacturers from this yolk by investigating internal virus proteins including M2e and NP as “universal” vaccines covering all virus sub types. Recent technical innovations have been the use of Vero and MDCK cells as the virus cell substrate, the testing of two new adjuvants and the exploration of new presentations to the nose or epidermal layers as DNA or antigen mixtures. The international investment into public health measures for a global human outbreak of avian H5N1 influenza is leading to enhanced production of conventional vaccine and to a new research searchlight on T cell epitope vaccines, viral live attenuated carriers of influenza proteins and even more innovative substrates to cultivate virus, including plant cells.
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References
Phillips H, Killingray D (2002) The Spanish influenza pandemic of 1918-1919: New perspectives. Routledge Social History of Medicine Series
Churchill WS (1993) The Great War, Vols 1 and 2. George Newnes Ltd, London
Crosby AW (1918) America’s Forgotten Pandemic. Cambridge University Press, New York
Medical Research Committee (1919) Special Report Series No 36. Studies of influenza in Hospitals of the British Armies in France, 1918. HM Stationery Office, London, 112
Reports on the Pandemic of Influenza 1918-1919 (1920) Reports on Public Health and Medical subjects, No 4. Stationery Office, London
Oxford JS (2000) Influenza A Pandemics of the 20th century with special reference to 1918: Virology, pathology and epidemiology. Rev Med Virol 10: 119–133
Macpherson WG, Herringham WP, Elliott TR, Balfour A (1927) Medical Services Diseases of the War. Vol. 2. Medical Aspects of Aviation and Gas Warfare and Gas Poisoning. HMSO, London
Collier L, Oxford JS (2007) Human Virology: A Text for Students of Medicine. Oxford University Press, Oxford
Stuart-Harris CH, Schild GC, Oxford JS (1983) Influenza: The Viruses and the Disease. Edward Arnold, London
Ferguson NM, Cummings DA, Cauchemez S, Fraser C, Riley S, Meeyai A, Iamsirithaworn S, Burke DS (2005) Strategies for containing an emerging influenza pandemic in Southeast Asia. Nature 437: 209–214
Barry JM (2004) The Great Influenza, the epic story of the deadliest plague in history. Viking, New York
Oxford JS (2005) Preparing for the first influenza pandemic of the 21st century. Lancet Infect Dis 5: 129–132
Oxford JS, Lambkin-Williams R, Sefton A, Daniels R, Elliot A, Brown R Gill D (2005) A hypothesis: The conjunction of soldiers, gas, pigs, ducks, geese and horses in Northern France during the Great War provided the conditions for the emergence of the “Spanish” influenza pandemic of 1918-1919. Vaccine 23: 940–945
Miller GL, Stanley WM (1944) Quantative aspects of the red blood cell agglutination test for influenza virus. J Exp Med 79: 185
Burnet FM (1941) Growth of influenza virus in the allantoic cavity of the chick embryo. Aus J Exp Biol Med Sci 19: 291
Hobson D, Curry RL, Beare AS, Word-Gardner A (1972) The role of serum HI antibody in protein against challenge infection with influenza A and B viruses. J Hyg 70: 767–777
Schild GC, Wood TM, Newman RW (1975) A single radial immunodiffusion technique for the assay of haemagglutinin antigen. WHO Bull 52: 223–231
Palese P, Schulman JL (1976) Mapping of the influenza virus genome: Identification of the haemagglutinin and neuraminidase genes. Proc Natl Acad Sci USA 73: 2142–2146
Hoffman E, Neumann G, Kawaoka Y, Hoborn G, Webster RG (2000) A DNA transfection system for generation of influenza A virus from eight plasmids. Proc Natl Acad Sci USA 97: 6108–6113
Schickli JH, Flandorfer A, Nakaya T, Martinez-Sobrido L, Garcia-Sastre A, Palese P (2001) Plasmid-only rescue of influenza A virus vaccine candidates. Philos Trans R Soc London B 356: 1965–1973
Kistner O, Barrett PN, Mundt W, Reiter M, Schober-Bendixen S, Dorner F (1998) Development of a mammalian cell (Vero) derived candidate influenza virus vaccine. Vaccine 16: 960–968
Palache AM, Brands R, van Scharrenburg G (1997) Immunogenicity and reactogenicity of influenza subunit vaccines produced in MDCK cells or fertilised chicken eggs. J Infect Dis (Suppl 1): S20–S23
Francis T Jr, Nagill TP (1935) Immunological studies with the virus of influenza. J Exp Med 62: 505
Andrewes CH, Smith W (1937) Influenza: Further experiments on the active immunisation of mice. Br J Exp Pathol 18: 43
Commission on Influenza, Board of Influenza and other epidemic diseases in the Army (1944) A clinical evaluation of vaccination against influenza. J Am Med Assoc 124: 982
Davenport FM, Hennessy AV, Brandon FM, Webster RG, Barrett CD Jr, Lease GO (1964) Comparisons of serological and febrile responses in humans to vaccination with influenza viruses or their haemagglutinins. J Lab Clin Med 63: 5–13
Brandon FB, Cox F, Lease GO, Timm EA, Quinn E, McLean IW Jr (1967) Respiratory virus vaccines. III. Some biological properties of sephadex-purified ether-extracted influenza virus antigens. J Immunol 98: 800–805
Duxbury AE, Hampson AW, Sievers JGM (1968) Antibody response in humans to deoxycholate-treated influenza virus vaccines. J Immunol 101: 62–67
Francis T Jr, Salk JE, Quilligan JJ Jr (1947) Experience with vaccination against influenza in the Spring of 1947. Am J Public Health 37: 1013–1016
Loosli CG, Schoenberger J, Barnett G (1948) Results of vaccination against influenza during the epidemic of 1947. J Lab Clin Med 33: 789
Kilbourne ED (1969) Future influenza vaccines and use of genetic recombinants. Bull World Health Organ 41: 643–645
Reimer CB, Baker RS, van Frank RM, Newlin TE, Cline GB, Anderson NG (1967) Purification of large quantities of influenza virus by density-gradient centrifugation. J Virol 1:1207–1216
Glezen WP, Loda FA, Denny FW (1969) A field evaluation of inactivated, zonal-centrifuged influenza vaccines in children in Chapel Hill, North Carolina, 1968-1969. Bull World Health Organ 41: 566–569
Salk JE (1948) Reactions to concentrated influenza vaccines. J Immunol 58: 369
Potter CW, Jennings R, Clark A (1977) The antibody response and immunity to challenge infection induced by whole inactivated and Tween-Ether split influenza vaccines. Dev Biol Stand 39: 323–328
Ennis FA, Mayner RE, Barry DW, Manischewitz JE, Dunlap RC, Verbonitz MW, Bozeman RM, Schild GC (1977) Correlation of laboratory studies with clinical responses to A/New Jersey influenza vaccines. J Infect Dis (Suppl) 136: S397–406
Wood JM, Schild GC, Newman RW Seagroatt V (1977) Application of an improved single-radial-immunodiffusion technique for the assay of influenza haemagglutinin antigen content of whole virus and subunit vaccines. Dev Biol Stand 39: 193–200
Holland WW, Isaacs A, Clarke SKR, Heath RB (1958) A serological trial of Asian influenza vaccine after the Autumn epidemic. Lancet I: 820–822
Nicholson KG, Tyrrell DAJ, Harrison P, Potter CW, Jennings R, Clark A (1979) Clinical studies of monovalent inactivated whole virus and subunit A/USSR/77 (H1N1) vaccine; serological responses and clinical reactions. J Biol Stand 7: 123–136
Mostow SR, Schoenbaum SC, Dowdle WR, Coleman MT, Kaye HS, Hierholzer JC (1970) Studies on inactivated influenza vaccines. II. Effect of increasing dosage on antibody with resistance to influenza in man. Am J Med 92: 248–256
Potter CW, Jennings R, Nicholson K, Tyrrell DAJ, Dickinson KG (1977) Immunity to attenuated influenza virus WRL 105 infection induced by heterologous, inactivated influenza A virus vaccines. J Hyg (Camb) 79: 321–332
Brady MI, Furminger IGS (1976) A surface antigen influenza vaccine 1. Purification of haemagglutinin and neuraminidase proteins. 2. Pyrogenicity and antigenicity. J Hyg (Camb) 77: 161–172
Pandemic Working Group of Medical Research Council’s Committee on Influenza and other respiratory virus vaccines (1977) Antibody responses and reactogenicity of graded doses of inactivated influenza A/New Jersey/76 wholevirus vaccine in humans. J Infect Dis 136: S475
Medical Research Council Committee on Influenza Vaccine (1953) Clinical trials of influenza vaccine. Br Med J 2: 1173–1173
Medical Research Council Committee on Influenza Vaccine (1957) Clinical trials of influenza vaccine Br Med J 2: 1–7
Medical Research Council Committee on Influenza Vaccine (1958) Trials of an Asian influenza vaccine. Br Med J 1: 415–418
Medical Research Council Committee on Influenza Vaccine (1964) Clinical trials of oil-adjuvant influenza vaccine, 1960-3. Br Med J 2: 267–271
Potter CW, Jennings R, Phair JP, Clarke A, Stuart-Harris CH (1977) Doseresponse relationship after immunisation of volunteers with a new surfaceantigenadsorbed influenza virus vaccine. J Infect Dis 135: 423–431
Kendal AP, Bozeman FM, Ennis FA (1980) Further studies of the neuraminidase content of inactivated influenza vaccines and the neuraminidase antibody responses after vaccination of immunologically primed and unprimed populations. Infect Immun 29: 966–971
Webster RG, Kasel JA, Couch RB, Laver WG (1976) Influenza virus subunit vaccines. II. Immunogenicity and original antigenic sin in humans. J Infect Dis 134: 48–58
Oxford JS, Schild GC, Potter C, Jennings R (1979) The specificity of the antihaemagluttinin antibody response induced in man by inactivated vaccines and by natural infection. J Hyg (Camb) 82: 51–56
Oxford JS, Haaheim LR, Slepushkin A, Werner J, Kuwert E, Schild GC (1981) Strain specificity of serum antibody to the haemagglutinin of influenza A (H3N2) viruses in children following immunisation or natural infection. J Hyg (Camb) 86: 17–26
Appleby JC, Himmelweit F, Stuart-Harris CH (1951) Influenza virus A vaccines. Comparison of intradermal and subcutaneous routes. Lancet 1: 1384–1387
McCarroll JR, Kilbourne ED (1958) Immunisation with Asian strain influenza vaccine-Equivalence of the subcutaneous and intradermal routes. N Engl J Med 259: 618–621
Tauraso NM, Gleckman R, Pedreira FA, Sabbaj J, Yahwak R, Madoff MA (1969) Effect of dosage and route of inoculation upon antigenicity of inactivated influenza virus vaccine (Hong Kong strain) in man. Bull World Health Organ 41: 507–516
Waldman RH, Case JA, Fulk RV, Togo Y, Hornick RB, Heiner GG, Dawkin Jun AT, Mann JJ (1968) Influenza antibody in human respiratory secretions after subcutaneous or respiratory immunisation with inactivated virus. Nature 218: 594–595
Waldman RH, Wigley FM, Small PA Jr (1970) Specificity of respiratory secretion antibody against influenza virus. J Immunol 105: 1477–1483
Phillips CA, Forsythe BR, Christmas WA, Gump DW, Whorton EB, Rogers I, Rudin A (1970) Purified influenza vaccine; clinical and serological response to varying doses and different routes of immunisation. J Infect Dis 122: 26–32
Potter CW, Stuart-Harris CH, McClaren C (1972) Antibody in respiratory secretions following immunisation with influenza virus vaccines. In, FT Perkins, RHS Regamey (eds): International Symposium Series Immunological standardisation 20. Karger, Basel, 198
Ruben FL, Potter CW, Stuart-Harris CH (1975) Humoral and secretory antibody responses to immunisation with low and high dosage split influenza virus vaccines. Arch Virol 47: 157–166
Downie JC, Stuart-Harris CH (1970) The production of neutralising activity in serum and nasal secretions following immunisation with influenza B virus. J Hyg (Camb) 68: 233–244
Ennis FA, Dowdle WR, Barry DW, Hochstein HD, Wright PF, Karzon DT, Marine WM, Meyer HM Jr (1977) Endotoxin content and clinical reactivity to influenza vaccines. J Biol Stand 5: 165–167
Wells CEC (1971) A neurological note on vaccinations against influenza. Br Med J 3: 755–756
Langmuir AD (1979) Guillain-Barré syndrome: The swine influenza virus vaccine incident in the United States of America, 1976-77. JR Soc Med 72: 660–669
Hurwitz ES, Schonberger LB, Nelson DB, Holman RC (1981) Guillain-Barré syndrome and the 1978-1979 influenza vaccine. N Engl J Med 304: 1557–1561
Mogabgab WJ, Liederman E (1970) Immunogenicity of 1967 polyvent and 1968 Hong Kong influenza vaccines. J Am Med Assoc 211: 1672–1676
Knight V, Couch RB, Douglas RG, Tauraso NM (1971) Serological responses and results of natural infectious challenge of recipients of zonal ultracentrifuged influenza.A2/AICHI/2/68 vaccine. Bull World Health Organ 45: 767–771
Mawson J, Swan C (1943) Intranasal vaccination of humans with living attenuated influenza virus strains. Med J Aust 1: 394
Stuart-Harris CH (1980) Present status of live influenza virus vaccine. J Infect Dis 142: 784
Kendal AP, Maasab H.F, Alexandrova GI, Ghendon YZ (1981) Development of cold-adapted recombinant live attenuated influenza A vaccines in the USA and USSR. Antiviral Res 1: 339
Beare AS, Bynoe ML, Tyrrell DAJ (1968) Investigation into attenuation of influenza viruses by serial passage. Br Med J 4: 482–484
Huygelen C, Petermans J, Vascoboinic E, Berge E, Colinet G (1973) Live attenuated influenza virus vaccine in vitro and in vivo properties. In: FT Perkins, RHS Regamey (eds): International Symposium on Influenza Vaccines for Man and Horses. Series Immunobiological Standards, vol 20. Karger, Basel, 152
Florent G, Lobmann M, Beare AS, Zygraich N (1977) RNA’s of influenza virus recombinants derived from parents of known virulence for man. Arch Virol 54: 19–28
Florent G (1980) Gene constellation of live influenza A vaccines. Arch Virol 64: 171–173
Beare AS, Hall TS (1971) Recombinant influenza A viruses as live vaccine for man. Lancet II: 1271–1271
Beare AS, Reed S (1977) The study of antiviral compounds in volunteers. In: JS Oxford (ed): Chemoprophylaxis and Viral Infections of the Respiratory Tract, vol 2. CRC Press, Cleveland, 27
Oxford JS, McGeoch DJ, Schild GC, Beare AS (1978) Analysis of virion RNA segments and polypeptides of influenza A virus recombinants of defined virulence. Nature 273:778–779
Jennings R, Potter CW, Teh CZ, Mahmud MI (1980) The replication of Type A influenza viruses in the infant rat: A marker for virus attenuation. J Gen Virol 49: 343–354
Murphy BR, Clements ML, Maasab HF, Buckler-White AJ, Tian S-F, London WT, Chanock RM (1984) The basis of attenuation of virulence of influenza virus for man. In: CH Stuart-Harris, CW Potter (eds): Molecular Virology and Epidemiology of Influenza. Academic Press, London, 211
Chanock RM, Murphy BR (1979) Genetic approaches to control of influenza. Perspect Biol Med 22: S37
Richman DD, Murphy BR, Chanock RM, Gwaltney JM Jr, Douglas RG, Betts RF, Blacklow NR, Rose FB, Parrino TA, Levine MM, Caplan ES (1976) Temperature-sensitive mutants of influenza A virus XII. Safety, antigenicity, transmissibility and efficacy of influenza A/Udorn/72-ts-1[E] recombinant viruses in human adults. J Infect Dis 134: 585–594
Maassab HF (1967) Adaptation and growth characteristics of influenza virus at 25 °C. Nature 213: 612–614
Maassab HF (1969) Biological and immunologic characteristics of cold-adapted influenza virus. J Immunol 102: 728–732
Spring SB, Maassab HF, Kendal AP, Murphy BR, Chanock RM (1977) Cold adapted variants of influenza A. II. Comparison of the genetic and biological properties of ts mutants and recombinants of the cold-adapted A/Ann Arbor/6/60 strain. Arch Virol 55: 233–246
Wright PF, Okabe N, McKee KT Jr, Maasab HF, Karzon DT (1982) Cold-adapted recombinant influenza A virus vaccines in young seronegative children. J Infect Dis 146: 71–79
Murphy BR, Tierney EL, Barbour BA, Yolken RH, Alling DW, Holley HP Jr, Mayner RE, Chanock RM (1980) Use of the enzyme-linked immunosorbent assay to detect serum antibody responses of volunteers who received attenuated influenza A virus vaccine. Infect Immun 29: 342–347
Alexandrova GI, Smorodintsev AA (1965) Obtaining of an additionally attenuated vaccinating cryophilic influenza strain. Roum Rev Inframicrobiol 2: 179
Alexieva RB, Petrova SM, Janceva BN (1971) Studies on some biological properties of vaccinal influenza strains cultivated at low temperatures. In: B Gusic (ed): Proceedings of the Symposium on Live Influenza Vaccine. Yugoslav Academy of science and Arts, Zagreb, 43
Zhilova GP, Alexandrova GI, Zykov MP, Smorodintsev AA (1977) Some problems with modern influenza prophylaxis with live vaccine. J Infect Dis 135: 681–686
Morris CA, Freestone DS, Stealey VM, Oliver PR (1975) Recombinant WRL 105 strain live attenuated influenza vaccine. Immunogenicity, reactivity and transmissibility. Lancet II: 196–199
Schild GC, Oxford JS, de Jong JC (1983) Evidence for host-cell selection of influenza virus antigenic variants. Nature 303: 706–709
Neiryncks S, Deroot T, Saelens X, Vanland Schoot P, Tou WM, Friers W (1999) A universal influenza A vaccine based on the extra cellular domain of the M2 protein. Nat Med 5: 1157–1163
Rimmelzwaan GF, Baars M, van Beek R, van Amerongen G, Lövgren-Bengtsson K, Claas EC, Osterhaus AD (1997) Induction of protective immunity against influenza virus in a macaque model: Comparison of conventional and ISCOM vaccines. J Gen Virol 78: 757–765
Britain V (1989) Testament of Youth: An Autobiographical Study of the Years 1900-1925. Penguin, New York
Gibson HG, Bowman FB, Connor JI (1919) The etiology of influenza: A filterable virus as the cause (with some notes on the culture of the virus by the method of Noguchi). In: Studies of Influenza in Hospitals of the British armies in France, 1918. HMSO, London, 36, 19–36
Henle W, Henle G, Stokes J Jr (1943) Demonstration of the efficacy of vaccination against influenza type A by experimental infection of human beings. J Immunol 46: 163
Bell JA, Ward TG, Kapikian AZ, Shelokov A, Reichelderfer TE, Huebner RJ (1957) Artificially induced Asian influenza in vaccinated and unvaccinated volunteers. J Am Med Assoc 165: 1366–1373
Couch RB (1975) Assessment of immunity to influenza virus using artificial challenge of normal volunteers with influenza virus. Dev Biol Stand 28: 295–306
Greenberg SB, Couch RB, Kasel JA (1973) Duration of immunity to type A influenza. Clin Res 21: 600
Schulman JL, Khakpour M, Kilbourne ED (1968) Protective effects of specific immunity to viral neuraminidase on influenza virus infection of mice. J Virol 2: 778–786
Beutner KR, Chow T, Rubi U, Strussenberg J, Clement J, Ogra PL (1979) Evaluation of a neuraminidase-specific influenza A virus vaccine in children. Antibody responses and effects on two successive outbreaks of natural infection. J Infect Dis 140: 844–850
Slepushkin AN, Schild GC, Beare AS, Chinn S, Tyrrell DAJ (1971) Neuraminidase and resistance to vaccination with live influenza A2 Hong Kong vaccine. J Hyg (Camb) 69: 571–578
Monto AS, Kendal AP (1973) Effect of neuraminidase antibody on Hong Kong influenza. Lancet I: 623–625
Larson HE, Tyrrell DAJ, Bowker CH, Potter CW, Schild GC (1978) Immunity to challenge in volunteers vaccinated with an inactivated current or earlier strain of influenza A (H3N2). J Hyg (Camb) 80: 243–248
Fazekas de St. Groth S, Hannoun C (1973) Sélection par pression immunologique de mutants dominants du virus de la grippe A (Hong Kong). C R Acad Sci de Paris D 276: 1917
Tyrrell D, Fielder M (2002) Cold Wars; The Fight Against the Common Cold. Oxford University Press, Oxford
Fries L, Lambkin-Williams R, Gelder C, White G, Burt D, Lowell G, Oxford J (2004) FluInsureTM, an inactivated trivalent influenza vaccine for intranasal administration, is protective in human challenge with A/Panama/2007/99 (H3N2) virus. In: Y Kawaoka (ed): Options for the Control of Influenza, V. International Congress Series. Elsevier, London, 1263, 661–665
Treanor JJ, Hayden FG (1998) Volunteer challenge studies. In: KG Nicholson, RG Webster, AJ Hay (eds): Textbook of Influenza. Blackwell Science, Oxford
Jones S, Evans K, McElwaine-John H, Sharpe M, Oxford J, Lambkin-Williams R, Mant T, Nolan A, Zambon M (2008) DNA vaccination protects against an influenza challenge in a phase 1b double blind randomised placebo controlled clinical trial (submitted)
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Oxford, J., Lambkin-Williams, R., Gilbert, A. (2008). Influenza vaccines have a short but illustrious history. In: Rappuoli, R., Del Giudice, G. (eds) Influenza Vaccines for the Future. Birkhäuser Advances in Infectious Diseases. Birkhäuser Basel. https://doi.org/10.1007/978-3-7643-8371-8_3
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