Safety and immunogenicity of modified vaccinia Ankara in hematopoietic stem cell transplant recipients: a randomized, controlled trial.

Abstract

BACKGROUND:

Modified vaccinia Ankara (MVA-BN, IMVAMUNE) is emerging as a primary immunogen and as a delivery system to treat or prevent a wide range of diseases. Defining the safety and immunogenicity of MVA-BN in key populations is therefore important.

METHODS:

We performed a dose-escalation study of MVA-BN administered subcutaneously in 2 doses, one on day 0 and another on day 28. Twenty-four hematopoietic stem cell transplant recipients were enrolled sequentially into the study, and vaccine or placebo was administered under a randomized, double-blind allocation. Ten subjects received vaccine containing 10(7) median tissue culture infective doses (TCID50) of MVA-BN, 10 subjects received vaccine containing 10(8) TCID50 of MVA-BN, and 4 subjects received placebo.

RESULTS:

MVA-BN was generally well tolerated at both doses. No vaccine-related serious adverse events were identified. Transient local reactogenicity was more frequently seen at the higher dose. Neutralizing antibodies (NAb) to Vaccinia virus (VACV) were elicited by both doses of MVA-BN and were greater for the higher dose. Median peak anti-VACV NAb titers were 1:49 in the lower-dose group and 1:118 in the higher-dose group. T-cell immune responses to VACV were detected by an interferon γ enzyme-linked immunosorbent spot assay and were higher in the higher-dose group.

CONCLUSIONS:

MVA-BN is safe, well tolerated, and immunogenic in HSCT recipients. These data support the use of 10(8) TCID50 of MVA-BN in this population.

CLINICAL TRIALS REGISTRATION:

NCT00565929.

• Authors: Stephen R Walsh, Marissa B Wilck, David J Dominguez, Elise Zablowsky, Shringkhala Bajimaya, Lisa S Gagne, Kelly A Verrill, Jane A Kleinjan, Alka Patel, Ying Zhang, Heather Hill, Aruna Acharyya, David C Fisher, Joseph H Antin, Michael S Seaman, Raphael Dolin, Lindsey R Baden
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 207 Issue 12 Pg. 1888-97 (Jun 15 2013) ISSN: 1537-6613 [Electronic] United States
• PMID: 23482644 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural)

Chemical References

• Antibodies, Neutralizing
• Antibodies, Viral
• Antigens, Viral
• Recombinant Proteins
• Smallpox Vaccine
• Vaccines, Attenuated
• imvamune

Topics

• Adult
• Antibodies, Neutralizing (biosynthesis)
• Antibodies, Viral (biosynthesis)
• Antigens, Viral (immunology)
• Cell Line
• Dose-Response Relationship, Immunologic
• Double-Blind Method
• Female
• Hematopoietic Stem Cell Transplantation (adverse effects)
• Humans
• Immunity, Cellular
• Immunocompromised Host
• Male
• Middle Aged
• Recombinant Proteins
• Smallpox Vaccine (administration & dosage, adverse effects, immunology)
• Vaccination
• Vaccines, Attenuated (administration & dosage, adverse effects, immunology)
• Vaccinia (immunology, prevention & control, virology)
• Vaccinia virus (genetics, immunology)
• Young Adult