Preclinical evaluation of Vaxfectin®-adjuvanted Vero cell-derived seasonal split and pandemic whole virus influenza vaccines

Human Vaccines and Immunotherapeutics

Volumn 9, Issue 6, 2013, Pages 1333-1345

  Smith, Larry R ^a   Wodal, Walter ^b   Crowe, Brian A ^b   Kerschbaum, Astrid ^b   Bruehl, Peter ^b   Schwendinger, Michael G ^b   Savidis Dacho, Helga ^b   Sullivan, Sean M ^a   Shlapobersky, Mark ^a   Hartikka, Jukka ^a   Rolland, Alain ^a   Barrett, P Noel ^b   Kistner, Otfried ^b  

^a VICAL INC   (United States)

^b BAXTER BIOSCIENCE   (Austria)

Author keywords

Adjuvant; Cationic liposomes; H5N1; Influenza vaccine; Vaxfectin ; Vero cell culture

Indexed keywords

GAMMA INTERFERON; INFLUENZA VACCINE; INTERLEUKIN 4; UNCLASSIFIED DRUG; VAXFECTIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIBODY RESPONSE; ANTIBODY TITER; ARTICLE; CELLULAR IMMUNITY; CONTROLLED STUDY; DRUG POTENCY; DRUG SAFETY; DRUG STABILITY; ENZYME LINKED IMMUNOSPOT ASSAY; FEMALE; GUINEA PIG; HEMAGGLUTINATION INHIBITION; HUMORAL IMMUNITY; IMMUNOGENICITY; INFLUENZA VIRUS A H5N1; MOUSE; NONHUMAN; PANDEMIC INFLUENZA; SEASONAL INFLUENZA; T LYMPHOCYTE; VERO CELL;

ADJUVANT; CATIONIC LIPOSOMES; H5N1; INFLUENZA VACCINE; VAXFECTIN®; VERO CELL CULTURE;

ADJUVANTS, IMMUNOLOGIC; ANIMALS; ANTIBODIES, VIRAL; FEMALE; GUINEA PIGS; HEMAGGLUTINATION INHIBITION TESTS; INFLUENZA A VIRUS; INFLUENZA VACCINES; INTERFERON-GAMMA; MICE; MICE, INBRED BALB C; PHOSPHATIDYLETHANOLAMINES; T-LYMPHOCYTES; TREATMENT OUTCOME; VACCINES, SUBUNIT;

EID: 84880653197     PISSN: 21645515     EISSN: 2164554X     Source Type: Journal    
DOI: 10.4161/hv.24209     Document Type: Article

References (58)

1. Girard MP, Cherian T, Pervikov Y, Kieny MP. A review of vaccine research and development: human acute respiratory infections. Vaccine 2005; 23:5708-24; PMID:16154667; http://dx.doi.org/10.1016/j.vaccine. 2005.07.046.
2. Thompson MG. Estimates of Deaths Associated with Seasonal Influenza-United States, 1976-2007. Morb Mortal Wkly Rep 2010; 59:1057-62.
3. Molinari NA, Ortega-Sanchez IR, Messonnier ML, Thompson WW, Wortley PM, Weintraub E, et al. The annual impact of seasonal influenza in the US: measuring disease burden and costs. Vaccine 2007; 25:5086-96; PMID:17544181; http://dx.doi.org/10.1016/j.vaccine. 2007.03.046.
4. Imai M, Watanabe T, Hatta M, Das SC, Ozawa M, Shinya K, et al. Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets. Nature 2012; 486:420-8; PMID:22722205.
5. Ohmit SE, Petrie JG, Cross RT, Johnson E, Monto AS. Influenza hemagglutination-inhibition antibody titer as a correlate of vaccine-induced protection. J Infect Dis 2011; 204:1879-85; PMID:21998477; http://dx.doi.org/10. 1093/infdis/jir661.
6. Osterholm MT, Kelley NS, Sommer A, Belongia EA. Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis. Lancet Infect Dis 2012; 12:36-44; PMID:22032844; http://dx.doi.org/10.1016/ S1473-3099(11)70295-X.
7. Treanor JJ, Talbot HK, Ohmit SE, Coleman LA, Thompson MG, Cheng PY, et al.; US Flu-VE Network. Effectiveness of seasonal influenza vaccines in the United States during a season with circulation of all three vaccine strains. Clin Infect Dis 2012; 55:951-9; PMID:22843783; http://dx.doi.org/10.1093/cid/ cis574.
8. Jefferson T, Rivetti D, Rivetti A, Rudin M, Di Pietrantonj C, Demicheli V. Efficacy and effectiveness of influenza vaccines in elderly people: a systematic review. Lancet 2005; 366:1165-74; PMID:16198765; http://dx.doi.org/ 10.1016/S0140-6736(05)67339-4.
9. Simonsen L, Reichert TA, Viboud C, Blackwelder WC, Taylor RJ, Miller MA. Impact of influenza vaccination on seasonal mortality in the US elderly population. Arch Intern Med 2005; 165:265-72; PMID:15710788; http://dx.doi.org/10.1001/archinte.165.3.265.
10. Falsey AR, Treanor JJ, Tornieporth N, Capellan J, Gorse GJ. Randomized, double-blind controlled phase 3 trial comparing the immunogenicity of high-dose and standard-dose influenza vaccine in adults 65 years of age and older. J Infect Dis 2009; 200:172-80; PMID:19508159; http://dx.doi.org/10.1086/599790.
11. Holland D, Booy R, De Looze F, Eizenberg P, McDonald J, Karrasch J, et al. Intradermal influenza vaccine administered using a new microinjection system produces superior immunogenicity in elderly adults: a randomized controlled trial. J Infect Dis 2008; 198:650-8; PMID:18652550; http://dx.doi.org/10.1086/ 590434.
12. Guy B. The perfect mix: recent progress in adjuvant research. Nat Rev Microbiol 2007; 5:505-17; PMID:17558426; http://dx.doi.org/10.1038/nrmicro1681.
13. Dormitzer PR, Tsai TF, Del Giudice G. New technologies for influenza vaccines. Hum Vaccin Immunother 2012; 8:45-58; PMID:22251994.
14. Coffman RL, Sher A, Seder RA. Vaccine adjuvants: putting innate immunity to work. Immunity 2010; 33:492-503; PMID:21029960; http://dx.doi.org/10.1016/j. immuni.2010.10.002.
15. O'Hagan DT, De Gregorio E. The path to a successful vaccine adjuvant-'the long and winding road'. Drug Discov Today 2009; 14:541-51; PMID:19508916; http://dx.doi.org/10.1016/j.drudis.2009.02.009.
16. Ferguson M, Risi G, Davis M, Sheldon E, Baron M, Li P, et al. Safety and long-term humoral immune response in adults after vaccination with an H1N1 2009 pandemic influenza vaccine with or without AS03 adjuvant. J Infect Dis 2012; 205:733-44; PMID:22315336; http://dx.doi.org/10.1093/infdis/jir641.
17. Jackson LA, Chen WH, Stapleton JT, Dekker CL, Wald A, Brady RC, et al. Immunogenicity and safety of varying dosages of a monovalent 2009 H1N1 influenza vaccine given with and without AS03 adjuvant system in healthy adults and older persons. J Infect Dis 2012; 206:811-20; PMID:22782949; http://dx.doi.org/10. 1093/infdis/jis427.
18. Vesikari T, Knuf M, Wutzler P, Karvonen A, Kieninger-Baum D, Schmitt HJ, et al. Oil-in-water emulsion adjuvant with influenza vaccine in young children. N Engl J Med 2011; 365:1406-16; PMID:21995388; http://dx.doi.org/10.1056/ NEJMoa1010331.
19. McElhaney JE. The unmet need in the elderly: designing new influenza vaccines for older adults. Vaccine 2005; 23(Suppl 1):S10-25; PMID:15908062; http://dx.doi.org/10.1016/j.vaccine.2005.04.019.
20. Weinberger B, Herndler-Brandstetter D, Schwanninger A, Weiskopf D, Grubeck-Loebenstein B. Biology of immune responses to vaccines in elderly persons. Clin Infect Dis 2008; 46:1078-84; PMID:18444828; http://dx.doi.org/10. 1086/529197.
21. 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; 354:1343-51; PMID:16571878; http://dx.doi.org/10.1056/NEJMoa055778.
22. Leroux-Roels G. Unmet needs in modern vaccinology: adjuvants to improve the immune response. Vaccine 2010; 28(Suppl 3):C25-36; PMID:20713254; http://dx.doi.org/10.1016/j.vaccine.2010.07.021.
23. Lambert LC, Fauci AS. Influenza vaccines for the future. N Engl J Med 2010; 363:2036-44; PMID:21083388; http://dx.doi.org/10.1056/NEJMra1002842.
24. Barrett PN, Mundt W, Kistner O, Howard MK. Vero cell platform in vaccine production: moving towards cell culture-based viral vaccines. Expert Rev Vaccines 2009; 8:607-18; PMID:19397417; http://dx.doi.org/10.1586/erv.09.19.
25. Kistner O, Barrett PN, Mundt W, Reiter M, Schober-Bendixen S, Dorner F. Development of a mammalian cell (Vero) derived candidate influenza virus vaccine. Vaccine 1998; 16:960-8; PMID:9682344; http://dx.doi.org/10.1016/S0264- 410X(97)00301-0.
26. Kistner O, Barrett PN, Mundt W, Reiter M, Schober-Bendixen S, Eder G, et al. Development of a Vero cellderived influenza whole virus vaccine. Dev Biol Stand 1999; 98:101-10, discussion 111; PMID:10494963.
27. Hartikka J, Bozoukova V, Ferrari M, Sukhu L, Enas J, Sawdey M, et al. Vaxfectin enhances the humoral immune response to plasmid DNA-encoded antigens. Vaccine 2001; 19:1911-23; PMID:11228361; http://dx.doi.org/10.1016/S0264- 410X(00)00445-X.
28. Sullivan SM, Doukas J, Hartikka J, Smith L, Rolland A. Vaxfectin: a versatile adjuvant for plasmid DNAand protein-based vaccines. Expert Opin Drug Deliv 2010; 7:1433-46; PMID:21118032; http://dx.doi.org/10.1517/17425247.2010. 538047.
29. Smith LR, Wloch MK, Ye M, Reyes LR, Boutsaboualoy S, Dunne CE, et al. Phase 1 clinical trials of the safety and immunogenicity of adjuvanted plasmid DNA vaccines encoding influenza A virus H5 hemagglutinin. Vaccine 2010; 28:2565-72; PMID:20117262; http://dx.doi.org/10.1016/j.vaccine.2010.01.029.
30. Hartikka J, Bozoukova V, Yang CK, Ye M, Rusalov D, Shlapobersky M, et al. Vaxfectin, a cationic lipid-based adjuvant for protein-based influenza vaccines. Vaccine 2009; 27:6399-403; PMID:19552895; http://dx.doi.org/10.1016/j. vaccine.2009.06.014.
31. Wright PF. Vaccine preparedness-are we ready for the next influenza pandemic? N Engl J Med 2008; 358:2540-3; PMID:18550873; http://dx.doi.org/10. 1056/NEJMp0803650.
32. Barrett PN, Portsmouth D, Ehrlich HJ. Developing cell culture-derived pandemic vaccines. Curr Opin Mol Ther 2010; 12:21-30; PMID:20140813.
33. Barrett PN, Berezuk G, Fritsch S, Aichinger G, Hart MK, El-Amin W, et al. Efficacy, safety, and immunogenicity of a Vero-cell-culture-derived trivalent influenza vaccine: a multicentre, double-blind, randomised, placebo-controlled trial. Lancet 2011; 377:751-9; PMID:21329971; http://dx.doi.org/10.1016/S0140- 6736(10)62228-3.
34. Ehrlich HJ, Berezuk G, Fritsch S, Aichinger G, Singer J, Portsmouth D, et al. Clinical development of a Vero cell culture-derived seasonal influenza vaccine. Vaccine 2012; 30:4377-86; PMID:22172502; http://dx.doi.org/10.1016/j. vaccine.2011.11.114.
35. Ehrlich HJ, Singer J, Berezuk G, Fritsch S, Aichinger G, Hart MK, et al. A cell culture-derived influenza vaccine provides consistent protection against infection and reduces the duration and severity of disease in infected individuals. Clin Infect Dis 2012; 54:946-54; PMID:22267715; http://dx.doi.org/10.1093/cid/cir959.
36. Ehrlich HJ, Müller M, Oh HM, Tambyah PA, Joukhadar C, Montomoli E, et al.; Baxter H5N1 Pandemic Influenza Vaccine Clinical Study Team. A clinical trial of a whole-virus H5N1 vaccine derived from cell culture. N Engl J Med 2008; 358:2573-84; PMID:18550874; http://dx.doi.org/10.1056/NEJMoa073121.
37. Lorbetskie B, Wang J, Gravel C, Allen C, Walsh M, Rinfret A, et al. Optimization and qualification of a quantitative reversed-phase HPLC method for hemagglutinin in influenza preparations and its comparative evaluation with biochemical assays. Vaccine 2011; 29:3377-89; PMID:21397719; http://dx.doi.org/10.1016/j.vaccine.2011.02.090.
38. Rappuoli R, Dormitzer PR. Influenza: options to improve pandemic preparation. Science 2012; 336:1531-3; PMID:22723412; http://dx.doi.org/10.1126/ science.1221466.
39. Keitel WA, Atmar RL. Preparing for a possible pandemic: influenza A/H5N1 vaccine development. Curr Opin Pharmacol 2007; 7:484-90; PMID:17644429; http://dx.doi.org/10.1016/j.coph.2007.06.004.
40. Garçon N, Vaughn DW, Didierlaurent AM. Development and evaluation of AS03, an Adjuvant System containing a-tocopherol and squalene in an oilin-water emulsion. Expert Rev Vaccines 2012; 11:349-66; PMID:22380826; http://dx.doi.org/10.1586/erv.11.192.
41. Levie K, Leroux-Roels I, Hoppenbrouwers K, Kervyn AD, Vandermeulen C, Forgus S, et al. An adjuvanted, low-dose, pandemic influenza A (H5N1) vaccine candidate is safe, immunogenic, and induces cross-reactive immune responses in healthy adults. J Infect Dis 2008; 198:642-9; PMID:18576945; http://dx.doi.org/10.1086/590913.
42. O'Hagan DT. MF59 is a safe and potent vaccine adjuvant that enhances protection against influenza virus infection. Expert Rev Vaccines 2007; 6:699-710; PMID:17931151; http://dx.doi.org/10.1586/14760584.6.5.699.
43. Nohynek H, Jokinen J, Partinen M, Vaarala O, Kirjavainen T, Sundman J, et al. AS03 adjuvanted AH1N1 vaccine associated with an abrupt increase in the incidence of childhood narcolepsy in Finland. PLoS One 2012; 7:e33536; PMID:22470453; http://dx.doi.org/10.1371/journal.pone.0033536.
44. Barnier Quer C, Elsharkawy A, Romeijn S, Kros A, Jiskoot W. Cationic liposomes as adjuvants for influenza hemagglutinin: more than charge alone. Eur J Pharm Biopharm 2012; 81:294-302; PMID:22487055; http://dx.doi.org/10.1016/j. ejpb.2012.03.013.
45. Even-Or O, Samira S, Rochlin E, Balasingam S, Mann AJ, Lambkin-Williams R, et al. Immunogenicity, protective efficacy and mechanism of novel CCS adjuvanted influenza vaccine. Vaccine 2010; 28:6527-41; PMID:20412874; http://dx.doi.org/10.1016/j.vaccine.2010.04.011.
46. Rosenkrands I, Vingsbo-Lundberg C, Bundgaard TJ, Lindenstrøm T, Enouf V, van der Werf S, et al. Enhanced humoral and cell-mediated immune responses after immunization with trivalent influenza vaccine adjuvanted with cationic liposomes. Vaccine 2011; 29:6283-91; PMID:21722683; http://dx.doi.org/10.1016/j.vaccine.2011.06.040.
47. Wack A, Baudner BC, Hilbert AK, Manini I, Nuti S, Tavarini S, et al. Combination adjuvants for the induction of potent, long-lasting antibody and T-cell responses to influenza vaccine in mice. Vaccine 2008; 26:552-61; PMID:18162266; http://dx.doi.org/10.1016/j.vaccine.2007.11.054.
48. Mahnke YD, Saqr A, Hazenfeld S, Brady RC, Roederer M, Subbramanian RA. Age-related changes in durability and function of vaccine-elicited influenza-specific CD4(+) T-cell responses. Vaccine 2011; 29:8606-14; PMID:21939709; http://dx.doi.org/10.1016/j.vaccine.2011.09.019.
49. 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; 176:6333-9; PMID:16670345.
50. Pedersen GK, Madhun AS, Breakwell L, Hoschler K, Sjursen H, Pathirana RD, et al. T-helper 1 cells elicited by H5N1 vaccination predict seroprotection. J Infect Dis 2012; 206:158-66; PMID:22551811; http://dx.doi.org/10.1093/infdis/ jis330.
51. Wilkinson TM, Li CK, Chui CS, Huang AK, Perkins M, Liebner JC, et al. Preexisting influenza-specific CD4+ T cells correlate with disease protection against influenza challenge in humans. Nat Med 2012; 18:274-80; PMID:22286307; http://dx.doi.org/10.1038/nm.2612.
52. Doukas J, Morrow J, Bellinger D, Hilgert T, Martin T, Jones D, et al. Nonclinical biodistribution, integration, and toxicology evaluations of an H5N1 pandemic influenza plasmid DNA vaccine formulated with Vaxfectin®. Vaccine 2011; 29:5443-52; PMID:21641955; http://dx.doi.org/10.1016/j.vaccine.2011.05. 060.
53. Raviprakash K, Luke TC, Doukas J, Danko J, Porter K, Burgess T, et al. A dengue DNA vaccine formulated with Vaxfectin (®) is well tolerated, and elicits strong neutralizing antibody responses to all four dengue serotypes in New Zealand white rabbits. Hum Vaccin Immunother 2012; 8:8; PMID:23032166.
54. Shlapobersky M, Wei Q, Sullivan S, Vilalta A. Vaxfectin-adjuvanted seasonal influenza protein vaccine: correlation of systemic and local immunological markers with formulation parameters. Vaccine 2009; 27:6404-10; PMID:19607952; http://dx.doi.org/10.1016/j.vaccine.2009.06.087.
55. Kistner O, Howard MK, Spruth M, Wodal W, Brühl P, Gerencer M, et al. Cell culture (Vero) derived whole virus (H5N1) vaccine based on wild-type virus strain induces cross-protective immune responses. Vaccine 2007; 25:6028-36; PMID:17614165; http://dx.doi.org/10.1016/j.vaccine.2007.05.013.
56. Howard MK, Kistner O, Barrett PN. Pre-clinical development of cell culture (Vero)-derived H5N1 pandemic vaccines. Biol Chem 2008; 389:569-77; PMID:18953724; http://dx.doi.org/10.1515/BC.2008.060.
57. Wood JM, Schild GC, Newman RW, Seagroatt V. An improved single-radial-immunodiffusion technique for the assay of influenza haemagglutinin antigen: application for potency determinations of inactivated whole virus and subunit vaccines. J Biol Stand 1977; 5:237-47; PMID:408355; http://dx.doi.org/10.1016/S0092-1157(77)80008-5.
58. Stephenson I, Wood JM, Nicholson KG, Charlett A, Zambon MC. Detection of anti-H5 responses in human sera by HI using horse erythrocytes following MF59-adjuvanted influenza A/Duck/Singapore/97 vaccine. Virus Res 2004; 103:91-5; PMID:15163495; http://dx.doi.org/10.1016/j.virusres.2004.02.019.