Return of inactivated whole-virus vaccine for superior efficacy

Immunology and Cell Biology

Volumn 90, Issue 6, 2012, Pages 571-578

  Furuya, Yoichi ^a  

^a ALBANY MEDICAL COLLEGE   (United States)

Author keywords

inactivated virus vaccine; infectious disease; influenza virus

Indexed keywords

ALUMINUM POTASSIUM SULFATE; AS 03; CD8 ANTIGEN; EPITOPE; IMMUNOLOGICAL ADJUVANT; INACTIVATED VIRUS VACCINE; INFLUENZA VACCINE; MIFAMURTIDE; SQUALENE; TOLL LIKE RECEPTOR 7; UNCLASSIFIED DRUG;

ANTIBODY RESPONSE; CD8+ T LYMPHOCYTE; CELLULAR IMMUNITY; CROSS REACTION; CYTOTOXIC T LYMPHOCYTE; DRUG EFFICACY; DRUG FORMULATION; DRUG SAFETY; EPIDEMIC; GAMMA IRRADIATION; HUMAN; HUMORAL IMMUNITY; IMMUNE RESPONSE; IMMUNITY; IMMUNOGENICITY; IMMUNOSTIMULATION; INFLUENZA; INFLUENZA A (H1N1); INFLUENZA VACCINATION; INFLUENZA VIRUS A H1N1; INFLUENZA VIRUS A H2N2; INFLUENZA VIRUS A H3N2; INFLUENZA VIRUS A H5N1; MEMORY T LYMPHOCYTE; NONHUMAN; PANDEMIC; REVIEW; SWINE INFLUENZA; T LYMPHOCYTE ACTIVATION; TH1 CELL; TH1 TH2 BALANCE; ULTRAVIOLET IRRADIATION; VIRUS SHEDDING;

ANIMALS; ANTIBODIES, VIRAL; CROSS PROTECTION; EPITOPES; GAMMA RAYS; HUMANS; INFLUENZA A VIRUS; INFLUENZA A VIRUS, H1N1 SUBTYPE; INFLUENZA VACCINES; INFLUENZA, HUMAN; MICE; ORTHOMYXOVIRIDAE INFECTIONS; T-LYMPHOCYTES, CYTOTOXIC; VACCINES, INACTIVATED;

ANIMALIA; INFLUENZA A VIRUS; ORTHOMYXOVIRIDAE; SUIDAE;

EID: 84863721678     PISSN: 08189641     EISSN: 14401711     Source Type: Journal    
DOI: 10.1038/icb.2011.70     Document Type: Review

References (174)

1. Gerdil C. The annual production cycle for influenza vaccine. Vaccine 2003; 21: 1776-1779.
2. Renfrey S, Watts A. Morphological and biochemical characterization of influenza vaccines commercially available in the United Kingdom. Vaccine 1994; 12: 747-752.
3. Cox RJ, Brokstad KA. The postvaccination antibody response to influenza virus proteins. Apmis 1999; 107: 289-296.
4. Beyer WE, Palache AM, de Jong JC, Osterhaus AD. Cold-adapted live influenza vaccine versus inactivated vaccine: systemic vaccine reactions, local and systemic antibody response, and vaccine efficacy. A meta-analysis. Vaccine 2002; 20: 1340-1353.
5. Aymard M, Valette M, Lina B, Thouvenot D. Surveillance and impact of influenza in Europe. Groupe Regional d'Observation de la Grippe and European Influenza Surveillance Scheme. Vaccine 1999; 17(Suppl 1): S30-S41.
6. Klimov A, Simonsen L, Fukuda K, Cox N. Surveillance and impact of influenza in the United States. Vaccine 1999; 17(Suppl 1): S42-S46.
7. Floc'h F, Werner GH. Heterotypic protective immune reactions in mice infected with distinct serotypes of human influenza virus. Ann Microbiol (Paris) 1978; 129: 509-524.
8. Schulman JL, Kilbourne ED. Induction of partial specific heterotypic immunity in mice by a single infection with influenza a virus. J Bacteriol 1965; 89: 170-174.
9. Kreijtz JH, Bodewes R, van Amerongen G, Kuiken T, Fouchier RA, Osterhaus AD et al. Primary influenza A virus infection induces cross-protective immunity against a lethal infection with a heterosubtypic virus strain in mice. Vaccine 2007; 25: 612-620.
10. Sonoguchi T, Naito H, Hara M, Takeuchi Y, Fukumi H. Cross-subtype protection in humans during sequential, overlapping, and/or concurrent epidemics caused by H3N2 and H1N1 influenza viruses. J Infect Dis 1985; 151: 81-88.
11. McMichael AJ, Gotch FM, Noble GR, Beare PA. Cytotoxic T-cell immunity to influenza. N Engl J Med 1983; 309: 13-17.
12. Slepushkin AN. The effect of a previous attack of A1 influenza on susceptibility to A2 virus during the 1957 outbreak. Bull World Health Organ 1959; 20: 297-301.
13. Bodewes R, Kreijtz JH, Baas C, Geelhoed-Mieras MM, de Mutsert G, van Amerongen G et al. Vaccination against human influenza A/H3N2 virus prevents the induction of heterosubtypic immunity against lethal infection with avian influenza A/H5N1 virus. PLoS One 2009; 4: e5538.
14. Bodewes R, Kreijtz JH, Hillaire ML, Geelhoed-Mieras MM, Fouchier RA, Osterhaus AD et al. Vaccination with whole inactivated virus vaccine affects the induction of heterosubtypic immunity against influenza virus A/H5N1 and immunodominance of virus-specific CD8+ T-cell responses in mice. J Gen Virol 2010; 91: 1743-1753.
15. Bodewes R, Kreijtz JH, Geelhoed-Mieras MM, van Amerongen G, Verburgh RJ, van Trierum SE et al. Vaccination against seasonal influenza A/H3N2 virus reduces the induction of heterosubtypic immunity against influenza A/H5N1 virus infection in ferrets. J Virol 2011; 85: 2695-2702.
16. Webster RG. Immunity to influenza in the elderly. Vaccine 2000; 18: 1686-1689.
17. Provinciali M, Di Stefano G, Muzzioli M, Scarpazza P, Colombo D, Migliorino M et al. Impaired antibody response to influenza vaccine in institutionalized elderly. Ann NY Acad Sci 1994; 717: 307-314.
18. Huber VC, McKeon RM, Brackin MN, Miller LA, Keating R, Brown SA et al. Distinct contributions of vaccine-induced immunoglobulin G1 (IgG1) and IgG2a antibodies to protective immunity against influenza. Clin Vaccine Immunol 2006; 13: 981-990.
19. Hovden AO, Cox RJ, Madhun A, Haaheim LR. Two doses of parenterally administered split influenza virus vaccine elicited high serum IgG concentrations which effectively limited viral shedding upon challenge in mice. Scand J Immunol 2005; 62: 342-352.
20. Bungener L, Geeraedts F, Ter Veer W, Medema J,Wilschut J, Huckriede A. Alum boosts TH2-type antibody responses to whole-inactivated virus influenza vaccine in mice but does not confer superior protection. Vaccine 2008; 26: 2350-2359.
21. Geeraedts F, Bungener L, Pool J, ter Veer W, Wilschut J, Huckriede A. Whole inactivated virus influenza vaccine is superior to subunit vaccine in inducing immune responses and secretion of proinflammatory cytokines by DCs. Influenza Other Respi Viruses 2008; 2: 41-51.
22. Govaert TM, Thijs CT, Masurel N, Sprenger MJ, Dinant GJ, Knottnerus JA. The efficacy of influenza vaccination in elderly individuals. A randomized double-blind placebocontrolled trial. Jama 1994; 272: 1661-1665.
23. Muszkat M, Friedman G, Schein MH, Naveh P, Greenbaum E, Schlesinger M et al. Local SIgA response following administration of a novel intranasal inactivated influenza virus vaccine in community residing elderly. Vaccine 2000; 18: 1696-1699.
24. Thompson WW, Shay DK, Weintraub E, Brammer L, Cox N, Anderson LJ et al. Mortality associated with influenza and respiratory syncytial virus in the United States. Jama 2003; 289: 179-186.
25. Gavazzi G, Krause KH. Ageing and infection. Lancet Infect Dis 2002; 2: 659-666.
26. Brandriss MW, Betts RF, Mathur U, Douglas Jr. RG. Responses of elderly subjects to monovalent A/USSR/77 (H1N1) and trivalent A/USSR/77 (H1N1)-A/TEXAS/77 (H3N2)-B/Hong Kong/72 vaccines. Am Rev Respir Dis 1981; 124: 681-684.
27. Gross PA, Quinnan Jr. GV, Weksler ME, Setia U, Douglas Jr. RG. Relation of chronic disease and immune response to influenza vaccine in the elderly. Vaccine 1989; 7: 303-308.
28. Gravenstein S, Drinka P, Duthie EH, Miller BA, Brown CS, Hensley M et al. Efficacy of an influenza hemagglutinin-diphtheria toxoid conjugate vaccine in elderly nursing home subjects during an influenza outbreak. J Am Geriatr Soc 1994; 42: 245-251.
29. McElhaney JE, Xie D, Hager WD, Barry MB, Wang Y, Kleppinger A et al. T cell responses are better correlates of vaccine protection in the elderly. J Immunol 2006; 176: 6333-6339.
30. McElhaney JE, Ewen C, Zhou X, Kane KP, Xie D, Hager WD et al. Granzyme B: correlates with protection and enhanced CTL response to influenza vaccination in older adults. Vaccine 2009; 27: 2418-2425.
31. Kim JH, Skountzou I, Compans R, Jacob J. Original antigenic sin responses to influenza viruses. J Immunol 2009; 183: 3294-3301.
32. McElhaney JE, Meneilly GS, Lechelt KE, Beattie BL, Bleackley RC. Antibody response to whole-virus and split-virus influenza vaccines in successful ageing. Vaccine 1993; 11: 1055-1060.
33. Webster RG, Kasel JA, Couch RB, Laver WG. Influenza virus subunit vaccines. II. Immunogenicity and original antigenic sin in humans. J Infect Dis 1976; 134: 48-58.
34. Virelizier JL, Allison AC, Schild GC. Antibody responses to antigenic determinants of influenza virus hemagglutinin. II. Original antigenic sin: a bone marrow-derived lymphocyte memory phenomenon modulated by thymus-derived lymphocytes. J Exp Med 1974; 140: 1571-1578.
35. Grebe KM, Yewdell JW, Bennink JR. Heterosubtypic immunity to influenza A virus: where do we stand? Microbes Infect 2008; 10: 1024-1029.
36. Gotch F, McMichael A, Smith G, Moss B. Identification of viral molecules recognized by influenza-specific human cytotoxic T lymphocytes. J Exp Med 1987; 165: 408-416.
37. Yewdell JW, Bennink JR, Smith GL, Moss B. Influenza A virus nucleoprotein is a major target antigen for cross-reactive anti-influenza A virus cytotoxic T lymphocytes. Proc Natl Acad Sci USA 1985; 82: 1785-1789.
38. Zweerink HJ, Courtneidge SA, Skehel JJ, Crumpton MJ, Askonas BA. Cytotoxic T cells kill influenza virus infected cells but do not distinguish between serologically distinct type A viruses. Nature 1977; 267: 354-356.
39. Askonas BA, Taylor PM, Esquivel F. Cytotoxic T cells in influenza infection. Ann NY Acad Sci 1988; 532: 230-237.
40. Lee LY, Ha do LA, Simmons C, de Jong MD, Chau NV, Schumacher R et al. Memory T cells established by seasonal human influenza A infection cross-react with avian influenza A (H5N1) in healthy individuals. J Clin Invest 2008; 118: 3478-3490.
41. Kreijtz JH, de Mutsert G, van Baalen CA, Fouchier RA, Osterhaus AD, Rimmelzwaan GF. Cross-recognition of avian H5N1 influenza virus by human cytotoxic T-lymphocyte populations directed to human influenza A virus. J Virol 2008; 82: 5161-5166.
42. Alsharifi M, Furuya Y, Bowden TR, Lobigs M, Koskinen A, Regner M et al. Intranasal flu vaccine protective against seasonal and H5N1 avian influenza infections. PLoS One 2009; 4: e5336.
43. Furuya Y, Chan J, Regner M, Lobigs M, Koskinen A, Kok T et al. Cytotoxic T cells are the predominant players providing cross-protective immunity induced by {gamma}-irradiated influenza A viruses. J Virol 2010; 84: 4212-4221.
44. Furuya Y, Regner M, Lobigs M, Koskinen A, Mullbacher A, Alsharifi M. Effect of inactivation method on the cross-protective immunity induced by whole 'killed' influenza A viruses and commercial vaccine preparations. J Gen Virol 2010; 91: 1450-1460.
45. Epstein SL. Prior H1N1 influenza infection and susceptibility of Cleveland Family Study participants during the H2N2 pandemic of 1957: an experiment of nature. J Infect Dis 2006; 193: 49-53.
46. Pebody RG, McLean E, Zhao H, Cleary P, Bracebridge S, Foster K et al. Pandemic Influenza A (H1N1) 2009 and mortality in the United Kingdom: risk factors for death, April 2009 to March 2010. Euro Surveill 2010; 15: article 4.
47. Hancock K, Veguilla V, Lu X, Zhong W, Butler EN, Sun H et al. Cross-reactive antibody responses to the 2009 pandemic H1N1 influenza virus. N Engl J Med 2009; 361: 1945-1952.
48. Gras S, Kedzierski L, Valkenburg SA, Laurie K, Liu YC, Denholm JT et al. Crossreactive CD8+ T-cell immunity between the pandemic H1N1-2009 and H1N1-1918 influenza A viruses. Proc Natl Acad Sci USA 2010; 107: 12599-12604.
49. Berkhoff EG, Geelhoed-Mieras MM, Fouchier RA, Osterhaus AD, Rimmelzwaan GF. Assessment of the extent of variation in influenza A virus cytotoxic T-lymphocyte epitopes by using virus-specific CD8+ T-cell clones. J Gen Virol 2007; 88: 530-535.
50. Rimmelzwaan GF, Boon AC, Voeten JT, Berkhoff EG, Fouchier RA, Osterhaus AD. Sequence variation in the influenza A virus nucleoprotein associated with escape from cytotoxic T lymphocytes. Virus Res 2004; 103: 97-100.
51. Berkhoff EG, Boon AC, Nieuwkoop NJ, Fouchier RA, Sintnicolaas K, Osterhaus AD et al. A mutation in the HLA-B*2705-restricted NP383-391 epitope affects the human influenza A virus-specific cytotoxic T-lymphocyte response in vitro. J Virol 2004; 78: 5216-5222.
52. Rimmelzwaan GF, Berkhoff EG, Nieuwkoop NJ, Fouchier RA, Osterhaus AD. Functional compensation of a detrimental amino acid substitution in a cytotoxic-T-lymphocyte epitope of influenza a viruses by comutations. J Virol 2004; 78: 8946-8949.
53. Rimmelzwaan GF, Berkhoff EG, Nieuwkoop NJ, Smith DJ, Fouchier RA, Osterhaus AD. Full restoration of viral fitness by multiple compensatory co-mutations in the nucleoprotein of influenza A virus cytotoxic T-lymphocyte escape mutants. J Gen Virol 2005; 86: 1801-1805.
54. Bodewes R, Geelhoed-Mieras MM, Nieuwkoop NJ, Hanson JA, David CS, Fouchier RA et al. Redundancy of the influenza A virus-specific cytotoxic T lymphocyte response in HLA-B*2705 transgenic mice limits the impact of a mutation in the immunodominant NP(383-391) epitope on influenza pathogenesis. Virus Res 2011; 155: 123-130.
55. Beigel JH, Farrar J, Han AM, Hayden FG, Hyer R, de Jong MD et al. Avian influenza A (H5N1) infection in humans. N Engl J Med 2005; 353: 1374-1385.
56. Mullbacher A, Tha Hla R. In vivo administration of major histocompatibility complex class I-specific peptides from influenza virus induces specific cytotoxic T cell hyporesponsiveness. Eur J Immunol 1993; 23: 2526-2531.
57. Liao S, Li R, Li H, Yang J, Zeng X. [Long-term efficacy of plasma-derived hepatitis B vaccine among Chinese children-a 12-year follow-up]. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 1998; 20: 89-94.
58. Maruyama M, Lam KP, Rajewsky K. Memory B-cell persistence is independent of persisting immunizing antigen. Nature 2000; 407: 636-642.
59. Tuaillon E, Tabaa YA, Petitjean G, Huguet MF, Pajeaux G, Fondere JM et al. Detection of memory B lymphocytes specific to hepatitis B virus (HBV) surface antigen (HBsAg) from HBsAg-vaccinated or HBV-immunized subjects by ELISPOT assay. J Immunol Methods 2006; 315: 144-152.
60. McMichael AJ, Gotch FM, Dongworth DW, Clark A, Potter CW. Declining T-cell immunity to influenza, 1977-82. Lancet 1983; 2: 762-764.
61. Hammarlund E, Lewis MW, Hansen SG, Strelow LI, Nelson JA, Sexton GJ et al. Duration of antiviral immunity after smallpox vaccination. Nat Med 2003; 9: 1131-1137.
62. Takada A, Kuboki N, Okazaki K, Ninomiya A, Tanaka H, Ozaki H et al. Avirulent Avian influenza virus as a vaccine strain against a potential human pandemic. J Virol 1999; 73: 8303-8307.
63. Straetemans M, Buchholz U, Reiter S, Haas W, Krause G. Prioritization strategies for pandemic influenza vaccine in 27 countries of the European Union and the Global Health Security Action Group: a review. BMC Public Health 2007; 7: 236.
64. Livingston BD, Higgins D, Van Nest G. Evolving strategies for the prevention of influenza infection: potential for multistrain targeting. BioDrugs 2006; 20: 335-340.
65. Fiers W, De Filette M, Birkett A, Neirynck S, Min Jou W. A 'universal' human influenza A vaccine. Virus Res 2004; 103: 173-176.
66. Epstein SL, Kong WP, Misplon JA, Lo CY, Tumpey TM, Xu L et al. Protection against multiple influenza A subtypes by vaccination with highly conserved nucleoprotein. Vaccine 2005; 23: 5404-5410.
67. Ulmer JB, Fu TM, Deck RR, Friedman A, Guan L, DeWitt C et al. Protective CD4+ and CD8+ T cells against influenza virus induced by vaccination with nucleoprotein DNA. J Virol 1998; 72: 5648-5653.
68. Okuda K, Ihata A, Watabe S, Okada E, Yamakawa T, Hamajima K et al. Protective immunity against influenza A virus induced by immunization with DNA plasmid containing influenza M gene. Vaccine 2001; 19: 3681-3691.
69. Chen Z, Matsuo K, Asanuma H, Takahashi H, Iwasaki T, Suzuki Y et al. Enhanced protection against a lethal influenza virus challenge by immunization with both hemagglutinin-and neuraminidase-expressing DNAs. Vaccine 1999; 17: 653-659.
70. Mitchell JA, Green TD, Bright RA, Ross TM. Induction of heterosubtypic immunity to influenza A virus using a DNA vaccine expressing hemagglutinin-C3d fusion proteins. Vaccine 2003; 21: 902-914.
71. Zou P, Liu W, Chen YH. The epitope recognized by a monoclonal antibody in influenza A virus M2 protein is immunogenic and confers immune protection. Int Immunopharmacol 2005; 5: 631-635.
72. Frace AM, Klimov AI, Rowe T, Black RA, Katz JM. Modified M2 proteins produce heterotypic immunity against influenza A virus. Vaccine 1999; 17: 2237-2244.
73. Neirynck S, Deroo T, Saelens X, Vanlandschoot P, Jou WM, Fiers W. A universal influenza A vaccine based on the extracellular domain of the M2 protein. Nat Med 1999; 5: 1157-1163.
74. De Filette M, Min Jou W, Birkett A, Lyons K, Schultz B, Tonkyro A et al. Universal influenza A vaccine: optimization of M2-based constructs. Virology 2005; 337: 149-161.
75. Hovden AO, Cox RJ, Haaheim LR. Whole influenza virus vaccine is more immunogenic than split influenza virus vaccine and induces primarily an IgG2a response in BALB/c mice. Scand J Immunol 2005; 62: 36-44.
76. Beyer WE, Palache AM, Osterhaus AD. Comparison of serology and reactogenicity between influenza subunit vaccines and whole virus or split vaccines: a review and meta-analysis of the literature. Clin Drug Investig 1998; 15: 1-12.
77. Nicholson KG, Tyrrell DA, Harrison P, Potter CW, Jennings R, Clark A et al. Clinical studies of monovalent inactivated whole virus and subunit A/USSR/77 (H1N1) vaccine: serological responses and clinical reactions. J Biol Stand 1979; 7: 123-136.
78. Stephenson I, Nicholson KG, Gluck R, Mischler R, Newman RW, Palache AM et al. Safety and antigenicity of whole virus and subunit influenza A/Hong Kong/1073/99 (H9N2) vaccine in healthy adults: phase I randomised trial. Lancet 2003; 362: 1959-1966.
79. McLaren C, Verbonitz MW, Daniel S, Grubbs GE, Ennis FA. Effect of priming infection on serologic response to whole and subunit influenza virus vaccines in animals. J Infect Dis 1977; 136(Suppl): S706-S711.
80. Boyer KM, Cherry JD, Wright PF, Lerman SJ, Gross PA, Foy HM et al. Clinical reactions and serologic responses in healthy children aged six to 35 months after two-dose regimens of inactivated A/New Jersey/76 influenza virus vaccines. J Infect Dis 1977; 136(Suppl): S579-S583.
81. Geeraedts F, Goutagny N, Hornung V, Severa M, de Haan A, Pool J et al. Superior immunogenicity of inactivated whole virus H5N1 influenza vaccine is primarily controlled by Toll-like receptor signalling. PLoS Pathog 2008; 4: e1000138.
82. Quan FS, Compans RW, Nguyen HH, Kang SM. Induction of heterosubtypic immunity to influenza virus by intranasal immunization. J Virol 2008; 82: 1350-1359.
83. Takada A, Matsushita S, Ninomiya A, Kawaoka Y, Kida H. Intranasal immunization with formalin-inactivated virus vaccine induces a broad spectrum of heterosubtypic immunity against influenza A virus infection in mice. Vaccine 2003; 21: 3212-3218.
84. Tumpey TM, Renshaw M, Clements JD, Katz JM. Mucosal delivery of inactivated influenza vaccine induces B-cell-dependent heterosubtypic cross-protection against lethal influenza A H5N1 virus infection. J Virol 2001; 75: 5141-5150.
85. Ada G. Vaccines and vaccination. N Engl J Med 2001; 345: 1042-1053.
86. Stauffer F, El-Bacha T, Da Poian AT. Advances in the development of inactivated virus vaccines. Recent Pat Antiinfect Drug Discov 2006; 1: 291-296.
87. Howard-Flanders P. Factors affecting radiation injury to DNA in bacteria and bacterio-phage system. Brookhaven Symp Biol 1961; 14: 18-31.
88. Seah SK, Hucal G. The use of irradiated vaccine in immunization against experimental murine toxoplasmosis. Can J Microbiol 1975; 21: 1379-1385.
89. Jarrett WF, Jennings FW, Mc IW, Mulligan W, Urquhart GM. Immunological studies on Dictyocaulus viviparus infection; immunity produced by the administration of irradiated larvae. Immunology 1960; 3: 145-151.
90. Miller TA. Persistence of immunity following double vaccination of pups with x-irradiated Ancylostoma caninum larvae. J Parasitol 1965; 51: 705-711.
91. Hsu HF, Hsu SY, Osborne JW. Immunization against Schistosoma japonicum in rhesus monkeys produced by irradiated cercariae. Nature 1962; 194: 98-99.
92. Radke MG, Sadun EH. Resistance produced in mice by exposure to irradiated Schistosoma mansonicercariae. Exp Parasitol 1963; 13: 134-142.
93. Wellde BT, Sadun EH. Resistance produced in rats and mice by exposure to irradiated Plasmodium berghei. Exp Parasitol 1967; 21: 310-324.
94. Nussenzweig R, Vanderberg J, Most H. Protective immunity produced by the injection of x-irradiated sporozoites of Plasmodium berghei. IV. Dose response, specificity and humoral immunity. Mil Med 1969; 134: 1176-1182.
95. Duxbury RE, Anderson JS, Wellde BT, Sadun EH, Muriithi IE. Trypanosoma congolense: immunization of mice, dogs, and cattle with gamma-irradiated parasites. Exp Parasitol 1972; 32: 527-533.
96. Gordon M, Donaldson DM, Wright GG. Immunization of mice with irradiated Pasteurella tularensis. J Infect Dis 1964; 114: 435-440.
97. Landay ME, Wright GG, Pulliam JD, Finegold MJ. Toxicity of Pasteurella tularensis killed by ionizing radiation. J Bacteriol 1968; 96: 804-810.
98. Carpenter CM, Naylor-Foote AW, Taplin GV, Lawrence CA, Drake CL. Preliminary report on vaccines prepared from gamma-irradiated Mycobacterium tuberculosis and Brucella suis. Am Rev Tuberc 1959; 79: 374-377.
99. Datta SK, Okamoto S, Hayashi T, Shin SS, Mihajlov I, Fermin A et al. Vaccination with irradiated Listeria induces protective T cell immunity. Immunity 2006; 25: 143-152.
100. Campbell CH. Immunogenicity of bluetongue virus inactivated by gamma irradiation. Vaccine 1985; 3: 401-406.
101. Campbell CH, Barber TL, Knudsen RC, Swaney LM. Immune response of mice and sheep to bluetongue virus inactivated by gamma irradiation. Prog Clin Biol Res 1985; 178: 639-647.
102. Reitman M, Tonik EJ. Immunity to aerosol challenge in guinea pigs immunized with gamma-irradiated Venezuelan equine encephalitis vaccines. Appl Microbiol 1971; 21: 688-692.
103. Reitman M, Tribble Jr. HR, Green L. Gamma-irradiated Venezuelan equine encephalitis vaccines. Appl Microbiol 1970; 19: 763-767.
104. Wiktor TJ, Aaslestad HG, Kaplan MM. Immunogenicity of rabies virus inactivated by-propiolactone, acetylethyleneimine, and ionizing irradiation. Appl Microbiol 1972; 23: 914-918.
105. Marennikova SS, Macevic GR. Experimental study of the role of inactivated vaccine in two-step vaccination against smallpox. Bull World Health Organ 1975; 52: 51-56.
106. Matsevich GR, Svet-Moldavskaia IA. [Smallpox vaccine inactivated by gamma-rays: its antigenic and immunogenic properties]. Vopr Virusol 1970; 15: 316-322.
107. Polley JR. The use of gamma radiation for the preparation of virus vaccines. C J Microbiol (Canada) 1962; 8: 455-459.
108. Polley JR. Preparation of stable noninfective soluble influenza a antigen. II. Use of various reagents for neutralization of formaldehyde-treated antigens. Can J Med Sci 1952; 30: 194-198.
109. Sanakkayala N, Sokolovska A, Gulani J, Hogenesch H, Sriranganathan N, Boyle SM et al. Induction of antigen-specific Th1-type immune responses by gamma-irradiated recombinant Brucella abortus RB51. Clin Diagn Lab Immunol 2005; 12: 1429-1436.
110. Hiramoto RM, Galisteo AJ, do Nascimento N, de Andrade Jr. HF. 200 Gy sterilized Toxoplasma gondii tachyzoites maintain metabolic functions and mammalian cell invasion, eliciting cellular immunity and cytokine response similar to natural infection in mice. Vaccine 2002; 20: 2072-2081.
111. Müllbacher A, Ada GL, Hla RT. Gamma-irradiated influenza A virus can prime for a cross-reactive and cross-protective immune response against influenza A viruses. Immunol Cell Biol 1988; 66(Pt 2): 153-157.
112. Polley JR. Factors influencing inactivation of infectivity and hemagglutinin of influenza virus by gamma radiation. Can J Microbiol 1961; 7: 535-541.
113. Kulevich EE, Kosiakov PN. [Immunogenic properties of A2/Hongkong/1/68 influenza virus inactivated with gamma rays]. Vopr Virusol 1974; 6: 696-700.
114. Noack K, Tischner H, Brauniger S, Nordheim W, Pohl WD. [Long-term effect of oral immunization against influenza with a gamma ray-inactivated vaccine in mice]. Z Erkr Atmungsorgane 1986; 166: 286-289.
115. Braciale TJ, Yap KL. Role of viral infectivity in the induction of influenza virus-specific cytotoxic T cells. J Exp Med 1978; 147: 1236-1252.
116. Pang GT, Clancy RL, O'Reilly SE, Cripps AW. A novel particulate influenza vaccine induces long-term and broad-based immunity in mice after oral immunization. J Virol 1992; 66: 1162-1170.
117. Lidbury BA, Grissell TV, Sizer PJ, Pang GT, Clancy R, Cripps AW. Erythrocytes enhance the immunogenicity of oral vaccination with gamma irradiated influenza virus: increasing the dose of irradiation results in a significant diminution of lung IgA response. Vaccine 1997; 15: 1529-1537.
118. Bachmann MF, Kundig TM, Kalberer CP, Hengartner H, Zinkernagel RM. Formalin inactivation of vesicular stomatitis virus impairs T-cell-but not T-help-independent B-cell responses. J Virol 1993; 67: 3917-3922.
119. Ertl HCJ, Gerike RHW, Koszinowski UH. Virus-specific T-cell sensitization. Requirement for vaccinia virus-specific T-cell sensitization in vivo. Immunogenetics 1977; 4: 515.
120. Lamb RA, Choppin PW. The gene structure and replication of influenza virus. Annu Rev Biochem 1983; 52: 467-506.
121. Richardson JC, Akkina RK. NS2 protein of influenza virus is found in purified virus and phosphorylated in infected cells. Arch Virol 1991; 116: 69-80.
122. Yewdell J, Anton LC, Bacik I, Schubert U, Snyder HL, Bennink JR. Generating MHC class I ligands from viral gene products. Immunol Rev 1999; 172: 97-108.
123. Milzer A, Oppenheimer F, Levinson SO. A new method for the production of potent inactivated vaccines with ultraviolet irradiation: III. A completely inactivated poliomyelitis vaccine with the lansing strain in mice. J Immunol 1945; 50: 331-340.
124. Rep. PH. Public health weekly reports for May 30, 1947. Public Health Rep 1947; 62: 777-823.
125. Lowy RJ, Vavrina GA, LaBarre DD. Comparison of gamma and neutron radiation inactivation of influenza A virus. Antiviral Res 2001; 52: 261-273.
126. Jagger J, Pollard EC. Inactivation with fast charged particles of infectivity and hemagglutination in influenza A virus. Radiat Res 1956; 4: 1-19.
127. Goldblith SA. Manual on radiation sterilization of medical and biological materials, technical report series no. 149, International Atomic Energy Agency, Lancaster, Pa (1973). Radiat Bot 1975; 15: 309.
128. Migunov AI, Aron RA, Sirotkin AK, Chernina LF, Kuznetsov OK. [Physicochemical characteristics of an influenza virus population inactivated by gamma rays]. Radiobiologiia 1986; 26: 647-651.
129. Fridman AL, Ermolaev AI, Bichurina MA, Chubarova NI. [Effect of gamma radiation on the biological characteristics of purified influenza virus]. Tr Inst Im Pastera 1979; 52: 135-139.
130. De Flora S, Badolati G, Bernardi G. [On the inactivation of the A2 Hong-Kong influenza virus with gamma rays]. G Ig Med Prev 1969; 10: 403-410.
131. Frenzen PD, DeBess EE, Hechemy KE, Kassenborg H, Kennedy M, McCombs K et al. Consumer acceptance of irradiated meat and poultry in the United States. J Food Prot 2001; 64: 2020-2026.
132. Spaulding A, Wiegand BR, O'Rourke PD. Consumer knowledge and perceptions of food irradiation: ground beef study. J Food Distrib Res 2006; 37: 161-167.
133. Kaplan C. The antigenicity of gamma-irradiated vaccinia virus. J Hyg (Lond) 1960; 58: 391-398.
134. Jordan RT, Kempe LL. Inactivation of some animal viruses with gamma radiation from cobalt-60. Proc Soc Exp Biol Med 1956; 91: 212-215.
135. Smolko EE, Lombardo JH. Virus inactivation studies using ion beams, electron and gamma irradiation. Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms 2005; 236: 249-253.
136. Pollard E. Inactivation of viruses for vaccine purposes using ionizing radiation and heat. Yale J Biol Med 1957; 29: 436-443.
137. Elliott LH, McCormick JB, Johnson KM. Inactivation of Lassa, Marburg, and Ebola viruses by gamma irradiation. J Clin Microbiol 1982; 16: 704-708.
138. Lupton HW. Inactivation of Ebola virus with 60Co irradiation. J Infect Dis 1981; 143: 291.
139. Müllbacher A, Marshall ID, Blanden RV. Cross-reactive cytotoxic T cells to alphavirus infection. Scand J Immunol 1979; 10: 291-296.
140. Müllbacher A, Marshall ID, Ferris P. Classification of Barmah Forest virus as an alphavirus using cytotoxic T cell assays. J Gen Virol 1986; 67(Pt 2): 295-299.
141. Clemens R, Safary A, Hepburn A, Roche C, Stanbury WJ, Andre FE. Clinical experience with an inactivated hepatitis A vaccine. J Infect Dis 1995; 171(Suppl 1): S44-S49.
142. Cranage MP, Baskerville A, Ashworth LA, Dennis M, Cook N, Sharpe S et al. Intrarectal challenge of macaques vaccinated with formalin-inactivated simian immunodeficiency virus. Lancet 1992; 339: 273-274.
143. Shahzad A, Kohler G. Inactivated polio vaccine (IPV): a strong candidate vaccine for achieving global polio eradication program. Vaccine 2009; 27: 5293-5294.
144. Koch C, Jensen SS, Oster A, Houen G. A comparison of the immunogenicity of the native and denatured forms of a protein. Apmis 1996; 104: 115-125.
145. Ferguson M, Wood DJ, Minor PD. Antigenic structure of poliovirus in inactivated vaccines. J Gen Virol 1993; 74(Pt 4): 685-690.
146. Cranage MP, McBride BW, Rud EW. The simian immunodeficiency virus transmembrane protein is poorly immunogenic in inactivated virus vaccine. Vaccine 1995; 13: 895-900.
147. Rossio JL, Esser MT, Suryanarayana K, Schneider DK, Bess Jr. JW, Vasquez GM et al. Inactivation of human immunodeficiency virus type 1 infectivity with preservation of conformational and functional integrity of virion surface proteins. J Virol 1998; 72: 7992-8001.
148. Lupton HW, Lambert RD, Bumgardner DL, Moe JB, Eddy GA. Inactivated vaccine for Ebola virus efficacious in guineapig model. Lancet 1980; 2: 1294-1295.
149. Nair SP, Sen AK. A study on the immune response of sheep to foot and mouth disease virus vaccine type 'O' prepared with different inactivants and adjuvants. Acta Virol 1992; 36: 473-478.
150. Bachmann MF, Bast C, Hengartner H, Zinkernagel RM. Immunogenicity of a viral model vaccine after different inactivation procedures. Med Microbiol Immunol 1994; 183: 95-104.
151. Chin J, Magoffin RL, Shearer LA, Schieble JH, Lennette EH. Field evaluation of a respiratory syncytial virus vaccine and a trivalent parainfluenza virus vaccine in a pediatric population. Am J Epidemiol 1969; 89: 449-463.
152. Kim HW, Canchola JG, Brandt CD, Pyles G, Chanock RM, Jensen K et al. Respiratory syncytial virus disease in infants despite prior administration of antigenic inactivated vaccine. Am J Epidemiol 1969; 89: 422-434.
153. Ilyinskii PO, Gabai VL, Sunyaev SR, Thoidis G, Shneider AM. Toxicity of influenza A virus matrix protein 2 for mammalian cells is associated with its intrinsic proton-channeling activity. Cell Cycle 2007; 6: 2043-2047.
154. Previte JJ, Chang Y, el-Bisi HM. Detoxification of Salmonella typhimurium lipopolysaccharide by ionizing radiation. J Bacteriol 1967; 93: 1607-1614.
155. Waddington CS, Walker WT, Oeser C, Reiner A, John T, Wilkins S et al. Safety and immunogenicity of AS03B adjuvanted split virion versus non-adjuvanted whole virion H1N1 influenza vaccine in UK children aged 6 months-12 years: open label, randomised, parallel group, multicentre study. BMJ 2010; 340: c2649.
156. Nicholson KG, Abrams KR, Batham S, Clark TW, Hoschler K, Lim WS et al. Immunogenicity and safety of a two-dose schedule of whole-virion and AS03Aadjuvanted 2009 influenza A (H1N1) vaccines: a randomised, multicentre, age-stratified, head-to-head trial. Lancet Infect Dis 2011; 11: 91-101.
157. Keitel WA, Dekker CL, Mink C, Campbell JD, Edwards KM, Patel SM et al. Safety and immunogenicity of inactivated, Vero cell culture-derived whole virus influenza A/H5N1 vaccine given alone or with aluminum hydroxide adjuvant in healthy adults. Vaccine 2009; 27: 6642-6648.
158. Ehrlich HJ, Muller M, Oh HM, Tambyah PA, Joukhadar C, Montomoli E et al. A clinical trial of a whole-virus H5N1 vaccine derived from cell culture. N Engl J Med 2008; 358: 2573-2584.
159. Ehrlich HJ, Muller M, Fritsch S, Zeitlinger M, Berezuk G, Low-Baselli A et al. A cell culture (Vero)-derived H5N1 whole-virus vaccine induces cross-reactive memory responses. J Infect Dis 2009; 200: 1113-1118.
160. Leroux-Roels I, Borkowski A, Vanwolleghem T, Drame M, Clement F, Hons E et al. Antigen sparing and cross-reactive immunity with an adjuvanted rH5N1 prototype pandemic influenza vaccine: a randomised controlled trial. Lancet 2007; 370: 580-589.
161. Treanor JJ, Campbell JD, Zangwill KM, Rowe T, Wolff M. Safety and immunogenicity of an inactivated subvirion influenza A (H5N1) vaccine. N Engl J Med 2006; 354: 1343-1351.
162. Treanor JJ, Wilkinson BE, Masseoud F, Hu-Primmer J, Battaglia R, O'Brien D et al. Safety and immunogenicity of a recombinant hemagglutinin vaccine for H5 influenza in humans. Vaccine 2001; 19: 1732-1737.
163. Bresson JL, Perronne C, Launay O, Gerdil C, Saville M, Wood J et al. Safety and immunogenicity of an inactivated split-virion influenza A/Vietnam/1194/2004 (H5N1) vaccine: phase I randomised trial. Lancet 2006; 367: 1657-1664.
164. Nicholson KG, Colegate AE, Podda A, Stephenson I, Wood J, Ypma E et al. Safety and antigenicity of non-adjuvanted and MF59-adjuvanted influenza A/Duck/Singapore/97 (H5N3) vaccine: a randomised trial of two potential vaccines against H5N1 influenza. Lancet 2001; 357: 1937-1943.
165. Ichinohe T, Tamura S, Kawaguchi A, Ninomiya A, Imai M, Itamura S et al. Cross-protection against H5N1 influenza virus infection is afforded by intranasal inoculation with seasonal trivalent inactivated influenza vaccine. J Infect Dis 2007; 196: 1313-1320.
166. Wrigley NG. Electron microscopy of influenza virus. Br Med Bull 1979; 35: 35-38.
167. Compans RW, Klenk HD, Caliguiri LA, Choppin PW. Influenza virus proteins. I. Analysis of polypeptides of the virion and identification of spike glycoproteins. Virology 1970; 42: 880-889.
168. Inglis SC, Carroll AR, Lamb RA, Mahy BW. Polypeptides specified by the influenza virus genome I. Evidence for eight distinct gene products specified by fowl plague virus. Virology 1976; 74: 489-503.
169. Hutchinson EC, Curran MD, Read EK, Gog JR, Digard P. Mutational analysis of cis-acting RNA signals in segment 7 of influenza A virus. J Virol 2008; 82: 11869-11879.
170. Stephenson I, Gust I, Pervikov Y, Kieny MP. Development of vaccines against influenza H5. Lancet Infect Dis 2006; 6: 458-460.
171. Radosevic K, Rodriguez A, Mintardjo R, Tax D, Bengtsson KL, Thompson C et al. Antibody and T-cell responses to a virosomal adjuvanted H9N2 avian influenza vaccine: impact of distinct additional adjuvants. Vaccine 2008; 26: 3640-3646.
172. Podda A, Del Giudice G. MF59-adjuvanted vaccines: increased immunogenicity with an optimal safety profile. Expert Rev Vaccines 2003; 2: 197-203.
173. Simon JK, Edelman R. Clinical evaluation of adjuvants. In: Immunopotentiators in Modern Vaccines. Schijins, VEJC and O'Hagan, DT (eds). Academic Press: London, 2006, pp 319-342.
174. Lewis DJ, Huo Z, Barnett S, Kromann I, Giemza R, Galiza E et al. Transient facial nerve paralysis (Bell's palsy) following intranasal delivery of a genetically detoxified mutant of Escherichia coli heat labile toxin. PLoS One 2009; 4: e6999.