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Clinical and Vaccine Immunology, September 2009, p. 1261-1271, Vol. 16, No. 9
1071-412X/09/$08.00+0     doi:10.1128/CVI.00040-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Comparative Evaluation of the Immune Responses and Protection Engendered by LC16m8 and Dryvax Smallpox Vaccines in a Mouse Model{triangledown}

Clement A. Meseda,1* Anne E. Mayer,1 Arunima Kumar,1 Alonzo D. Garcia,1 Joseph Campbell,1 Paul Listrani,1 Jody Manischewitz,2 Lisa R. King,2 Hana Golding,2 Michael Merchlinsky,1 and Jerry P. Weir1

Laboratory of DNA Viruses, Division of Viral Products, HFM-457, Center for Biologics Evaluation and Research, Food and Drug Administration, 1401 Rockville Pike, Rockville, Maryland 20852,1 Laboratory of Retrovirus Research, Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 208922

Received 29 January 2009/ Returned for modification 25 February 2009/ Accepted 29 June 2009

The immune response elicited by LC16m8, a candidate smallpox vaccine that was developed in Japan by cold selection during serial passage of the Lister vaccine virus in primary rabbit kidney cells, was compared to Dryvax in a mouse model. LC16m8 carries a mutation resulting in the truncation of the B5 protein, an important neutralizing target of the extracellular envelope form of vaccinia virus (EV). LC16m8 elicited a broad-spectrum immunoglobulin G (IgG) response that neutralized both EV and the intracellular mature form of vaccinia virus and provoked cell-mediated immune responses, including the activation of CD4+ and CD8+ cells, similarly to Dryvax. Mice inoculated with LC16m8 had detectable but low levels of anti-B5 IgG compared to Dryvax, but both Dryvax and LC16m8 sera neutralized vaccinia virus EV in vitro. A truncated B5 protein (~8 kDa) was expressed abundantly in LC16m8-infected cells, and both murine immune sera and human vaccinia virus immunoglobulin recognized the truncated recombinant B5 protein in antigen-specific enzyme-linked immunosorbent assays. At a high-dose intranasal challenge (100 or 250 50% lethal doses), LC16m8 and Dryvax conferred similar levels of protection against vaccinia virus strain WR postvaccination. Taken together, the results extend our current understanding of the protective immune responses elicited by LC16m8 and indicate that the relative efficacy in a mouse model rivals that of previously licensed smallpox vaccines.

* Corresponding author. Mailing address: Division of Viral Products, HFM-457, Center for Biologics Evaluation and Research, 1401 Rockville Pike, Rockville, MD 20852. Phone: (301) 827-2936. Fax: (301) 496-1810. E-mail: clement.meseda{at}fda.hhs.gov

{triangledown} Published ahead of print on 15 July 2009.

Clinical and Vaccine Immunology, September 2009, p. 1261-1271, Vol. 16, No. 9
1071-412X/09/$08.00+0     doi:10.1128/CVI.00040-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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