Development of VAX128, a recombinant hemagglutinin (HA) influenza-flagellin fusion vaccine with improved safety and immune response

Vaccine

Volumn 30, Issue 39, 2012, Pages 5761-5769

  Taylor, David N ^a   Treanor, John J ^b   Sheldon, Eric A ^c   Johnson, Casey ^d   Umlauf, Scott ^a   Song, Langzhou ^a   Kavita, Uma ^a   Liu, Ge ^a   Tussey, Lynda ^a   Ozer, Karen ^e   Hofstaetter, Thomas ^a   Shaw, Alan ^a  

^a VaxInnate Corporation   (United States)

^b UNIVERSITY OF ROCHESTER SCHOOL OF MEDICINE AND DENTISTRY   (United States)

^c MIAMI RESEARCH ASSOCIATES   (United States)

^d Johnson County Clin Trials   (United States)

^e Cytel Incorporated   (United States)

Author keywords

Flagellin adjuvant; Influenza prevention; Influenza vaccine; Recombinant vaccine; Vaccine

Indexed keywords

C REACTIVE PROTEIN; FLAGELLIN; INFLUENZA VACCINE; INFLUENZA VIRUS HEMAGGLUTININ; INTERLEUKIN 6; PLACEBO; RECOMBINANT VACCINE; TOLL LIKE RECEPTOR 5; UNCLASSIFIED DRUG; VAX 128A; VAX 128B; VAX 128C;

ADULT; AGED; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ANIMAL EXPERIMENT; ANTIBODY TITER; ARM PAIN; ARTHRALGIA; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; CARBOXY TERMINAL SEQUENCE; CHILL; CONFIDENCE INTERVAL; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; DRUG DESIGN; DRUG DOSE ESCALATION; DRUG FEVER; DRUG INDUCED HEADACHE; DRUG RESPONSE; DRUG SAFETY; DRUG TOLERABILITY; ECCHYMOSIS; FATIGUE; HEMAGGLUTINATION INHIBITION TEST; HUMAN; HUMAN EXPERIMENT; IMMUNE RESPONSE; IMMUNOGENICITY; INJECTION SITE INDURATION; INJECTION SITE PAIN; INJECTION SITE SWELLING; LEUKOCYTE COUNT; MULTICENTER STUDY; MYALGIA; NONHUMAN; NORMAL HUMAN; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; PROTEIN DOMAIN; RANDOMIZED CONTROLLED TRIAL; SEROCONVERSION; SERUM; SHIVERING; SIDE EFFECT; SINGLE DRUG DOSE; SWEATING;

ADJUVANTS, IMMUNOLOGIC; ADOLESCENT; ADULT; AGED; ANIMALS; ANTIBODIES, VIRAL; C-REACTIVE PROTEIN; DOUBLE-BLIND METHOD; FEMALE; FLAGELLIN; HEMAGGLUTINATION INHIBITION TESTS; HEMAGGLUTININ GLYCOPROTEINS, INFLUENZA VIRUS; HUMANS; INFLUENZA VACCINES; INFLUENZA, HUMAN; INTERLEUKIN-6; MALE; MIDDLE AGED; RABBITS; VACCINES, SYNTHETIC; YOUNG ADULT;

EID: 84864945063     PISSN: 0264410X     EISSN: 18732518     Source Type: Journal    
DOI: 10.1016/j.vaccine.2012.06.086     Document Type: Article

References (12)

1. Lambert L.C., Fauci A.S. Influenza vaccines for the future. N Engl J Med 2010, 363:2036-2044.
2. Song L., Nakaar V., Kavita U., Price A., Huleatt J., Tang J., et al. Efficacious recombinant influenza vaccines produced by high yield bacterial expression: a solution to global pandemic and seasonal needs. PLoS One 2008, 3:e2257.
3. Liu G., Tarbet B., Song L., Reiserova L., Weaver B., Chen Y., et al. Immunogenicity and efficacy of flagellin-fused vaccine candidates targeting 2009 pandemic H1N1 influenza in mice. PLoS One. 2011, 6:e20928.
4. Treanor J.J., Taylor D.N., Tussey L., Hay C., Nolan C., Fitzgerald T., et al. Safety and immunogenicity of a recombinant hemagglutinin influenza-flagellin fusion vaccine (VAX125) in healthy young adults. Vaccine 2010, 28:8268-8274.
5. Taylor D.N., Treanor J.J., Strout C., Johnson C., Fitzgerald T., Kavita U., et al. Induction of a potent immune response in the elderly using the TLR-5 agonist, flagellin, with a recombinant hemagglutinin influenza-flagellin fusion vaccine (VAX125, STF2.HA1 SI). Vaccine 2011, 29:4897-4902.
6. Song L., Zhang Y., Yun N.E., et al. Superior efficacy of a recombinant flagellin: H5N1 HA globular head vaccine is determined by the placement of the globular head within flagellin. Vaccine 2009, 27:5875-5884.
7. Dowdle W.N., Kendal A.P., Noble G.R. Influenza viruses. Diagnostic procedures for viral, rickettsial, and chlamydial infections 1979, 603-605. American Public Health Association, Washington, DC. 5th ed. E.H. Lenette, N.J. Schmidt (Eds.).
8. Black S., Kushner I., Samols D. C-reactive protein. J Biol Chem 2004, 279:48487-48490.
9. Smith K.D., Andersen-Nissen E., Hayashi F., Strobe K., Bergman M.A., Barrett S.L., et al. Toll-like receptor 5 recognizes a conserved site on flagellin required for protofilament formation and bacterial motility. Nat Immunol 2003, 4:1247-1253.
10. Andersen-Nissen E., Smith K.D., Strobe K.L., Barrett S.L., Cookson B.T., Logan S.M., et al. Evasion of toll-like receptor 5 by flagellated bacteria. Proc Natl Acad Sci USA 2005, 102:9247-9252.
11. Podolsky D.K. Inflammatory bowel disease. N Engl J Med 2002, 347:417-429.
12. Lodes M.J., Cong Y., Elson C.O., Mohamath R., Landers C.J., Targan S.R., et al. Bacterial flagellin is a dominant antigen in Crohn disease. J Clin Invest 2004, 113:1296-1306.