Phase II randomized, double-blinded comparison of a single high dose (5×108 TCID50) of modified vaccinia Ankara compared to a standard dose (1×108 TCID50) in healthy vaccinia-naïve individuals

Vaccine

Volumn 32, Issue 23, 2014, Pages 2732-2739

  Frey, Sharon E ^a   Winokur, Patricia L ^b   Hill, Heather ^c   Goll, Johannes B ^c   Chaplin, Paul ^d   Belshe, Robert B ^a  

^a SAINT LOUIS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF IOWA   (United States)

^c EMMES CORPORATION   (United States)

^d Bavarian Nordic GmbH   (Germany)

Author keywords

ELISA; IMVAMUNE; MVA; Plaque reduction neutralizing antibody; Smallpox; Vaccine; Variola

Indexed keywords

NEUTRALIZING ANTIBODY; SMALLPOX VACCINE;

ADULT; ANTIBODY TITER; ARTICLE; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; DRUG DOSE COMPARISON; DRUG MEGADOSE; DRUG SAFETY; DRUG TOLERABILITY; ENZYME LINKED IMMUNOSORBENT ASSAY; FATIGUE; FEMALE; FEVER; HEADACHE; HUMAN; IMMUNE RESPONSE; IMMUNOGENICITY; MALE; MULTICENTER STUDY; NORMAL HUMAN; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SEROCONVERSION; SINGLE DRUG DOSE; VACCINATION; VACCINATION REACTION; VACCINIA VIRUS;

ELISA; IMVAMUNE; MVA; PLAQUE REDUCTION NEUTRALIZING ANTIBODY; SMALLPOX; VACCINE; VARIOLA;

ADOLESCENT; ADULT; ANTIBODIES, NEUTRALIZING; ANTIBODIES, VIRAL; FEMALE; HUMANS; MALE; NEUTRALIZATION TESTS; SMALLPOX; SMALLPOX VACCINE; VIRAL PLAQUE ASSAY; YOUNG ADULT;

EID: 84899926008     PISSN: 0264410X     EISSN: 18732518     Source Type: Journal    
DOI: 10.1016/j.vaccine.2014.02.043     Document Type: Article

References (24)

1. Fenner F., Henderson D.A., Arita I., Jezek Z., Ladnyi I.D. Smallpox and its eradication 1988, 1-1460. World Health Organization, Geneva.
2. ACAM2000™ Smallpox Vaccine, Vaccines and Related Biological Products Advisory Committee (VRBPAC) Briefing Document; April 18, 2007 [Internet] [cited August 1, 2013], 70p. Available from:. http://www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4292b2-02.pdf.
3. Mayr A., Stickl H., Muller H.K., Danner K., Singer H. The smallpox vaccination strain MVA: marker, genetic structure, experience gained with the parenteral vaccination and behavior in organisms with a debilitated defence mechanism. Zentralbl Bakteriol 1978, 167:375-390.
4. Stickl H., Hochstein-Mintzel V., Mayr A., Huber H., Schäfer Ch., Holzner H.A. MVA vaccination against smallpox: clinical tests with an attenuated live vaccinia virus strain (MVA). Dtsch Med Wochenschr 1974, 99:2386-2392.
5. Antoine G., Scheiflinger F., Dorner F., Falkner F.G. The complete genomic sequence of the modified vaccinia Ankara strain: comparison with other orthopox viruses. Virology 1998, 244:365-366.
6. Rosel J.L., Earl P.L., Weir J.P., Moss B. Conserved TAAATG sequence at the transcriptional translational initiation sites of vaccinia virus late genes deduced by structural and functional analysis of the HindIII H genomic fragment. J Virol 1986, 6:436-449.
7. Meyer H., Sutter G., Mayr A. Mapping of deletions in the genome of the highly attenuated vaccinia virus MVA and their influence on virulence. J Gen Virol 1991, 72:1031-1038.
8. Sutter G., Moss B. Non-replicating vaccinia vector efficiently expresses recombinant genes. Proc Natl Acad Sci USA 1992, 89:10847-10851.
9. Carroll M.W., Moss B. Host range and cytopathogenicity of the highly attenuated MVA strain of vaccinia virus: propagation and generation of recombinant viruses in a non-human mammalian cell line. Virology 1997, 238:198-211.
10. Blanchard T.J., Alcami A., Andrea P., Smith G.L. Modified vaccinia virus Ankara undergoes limited replication in human cells and lacks several immunomodulatory proteins: implications for use as a human vaccine. J Gen Virol 1998, 79:1159-1167.
11. Drexler I., Heller K., Wahren B., Erfle V., Sutter G. Highly attenuated modified vaccinia virus Ankara replicates in baby hamster kidney cells, a potential host for virus propagation, but not in various human transformed and primary cells. Gen Virol 1998, 79:347-352.
12. Mayr A., Hochstein M., Mintzel V., Stickl H. Passage history, properties, and applicability of the attenuated vaccinia virus strain MVA. Infection 1975, 3:6-14.
13. Suter M., Meisinger-Henschel C., Tzatzaris M., Hulsemann V., Lukassen S., Wulff N.H., et al. Modified vaccinia Ankara strains with identical coding sequences actually represent complex mixtures of viruses that determine the biological properties of each strain. Vaccine 2009, 27:7442-7450.
14. Walsh S.R., Wilck M.B., Dominguez D.J., Zablowsky E., Bajimaya S., Gagne L.S., et al. Safety and immunogenicity of modified vaccinia Ankara in hematopoietic stem cell transplant recipients: a randomized controlled trial. J Infect Dis 2013, 207:1888-1897.
15. Greenberg R.N., Overton E.T., Haas D.W., Frank I., Goldman M., von Krempelhuber A., et al. Safety immunogenicity, and surrogate markers of clinical efficacy for modified vaccinia ankara as a smallpox vaccine in HIV-infected subjects. J Infect Dis 2013, 207:749-758.
16. Risk assessment tool for estimating your 10-year risk of having a heart attack. Available from: [accessed 19.12.13]. http://cvdrisk.nhlbi.nih.gov/calculator.asp.
17. ®. Vaccine 2010, 28:1209-1216.
18. Iacono-Connors L.C., Novak J., Rossi C., Mangiafico J., Ksiazek T. Enzyme-linked immunosorbent assay using a recombinant baculovirus-expressed Bacillus anthracis protective antigen (PA): measurement of human anti-PA antibodies. Clin Diagn Lab Immunol 1994, 1:78-82.
19. Hughes C., Newman F., Davidson W., Olson V., Smith S., Holman R., et al. Analysis of variola and vaccinia neutralization assays for smallpox vaccines. Clin Vaccine Immunol 2012, 19:1116-1118.
20. Pan W. Extending the iterative convex minorant algorithm to the cox model for interval-censored data. J Comput Graph Stat 1999, 8:109-120.
21. Efron B. Bootstrap methods: another look at the jackknife. Ann Stat 1979, 7:1-26.
22. Frey S.E., Newman F.K., Kennedy J.S., Sobek V., Ennis F.A., Hill H., et al. Clinical and immunologic responses to multiple doses of IMVAMUNE (R) (Modified Vaccinia Ankara) followed by Dryvax (R) challenge. Vaccine 2007, 25:8562-8573.
23. Seaman M.S., Wilck M.B., Baden L.R., Walsh S.R., Grandpre L.E., Devoy C., et al. Effect of vaccination with modified vaccinia Ankara (ACAM3000) on subsequent challenge with Dryvax. J Infect Dis 2010, 20:1353-1360.
24. Damon I.K., Davidson W.B., Hughes C.M., Olson V.A., Smith S.K., Holman R.C., et al. Evaluation of smallpox vaccines using variola neutralization. J Gen Virol 2009, 90:1962-1966.