Introduction.LC16m8 is an attenuated cell culture-adapted Lister vaccinia smallpox vaccine missing the B5R protein and licensed for use in Japan.Methods.We conducted a phase I/II clinical trial that compared the safety and immunogenicity of LC16m8 with Dryvax in vaccinia-naive participants. Adverse events were assessed, as were electrocardiography and laboratory testing for cardiotoxicity and viral culturing of the vaccination sites. Neutralization titers to vaccinia, monkeypox, and variola major were assessed and cell-mediated immune responses were measured by interferon (IFN)-γ enzyme-linked immunosorbent spot and lymphoproliferation assays.Results.Local and systemic reactions after vaccination with LC16m8 were similar to those reported after Dryvax. No clinically significant abnormalities consistent with cardiac toxicity were seen for either vaccine. Both vaccines achieved antivaccinia, antivariola, and antimonkeypox neutralizing antibody titers >1:40, although the mean plaque reduction neutralization titer of LC16m8 at day 30 after vaccination was significantly lower than Dryvax for anti-NYCBH vaccinia (P <. 01), antimonkeypox (P <. 001), and antivariola (P <. 001). LC16m8 produced robust cellular immune responses that trended higher than Dryvax for lymphoproliferation (P =. 06), but lower for IFN-γ ELISPOT (P =. 02).Conclusions.LC16m8 generates neutralizing antibody titers to multiple poxviruses, including vaccinia, monkeypox, and variola major, and broad T-cell responses, indicating that LC16m8 may have efficacy in protecting individuals from smallpox.Clinical Trials Registration.
|Number of pages||8|
|Journal||Journal of Infectious Diseases|
|State||Published - Nov 1 2011|
Bibliographical noteFunding Information:
Acknowledgments. The site clinical research teams included Beth Plummer, Ester Cook, Dana Hargis, Connie Geradeau, Nancy Johnson, Heather Vaughn, Steven Siztler, Susan Philips, Debbie Plummer, Stacy Plummer, Malissia Van Hook, and David Rudy (University of Kentucky); Sharon Irby-Moore and the staff of the Saint Louis University Center for Vaccine Development; Deborah Hunter (Vanderbilt University); Peter T. Rogge, MD (Solano Clinical Research); and Jose Montoya, Dora Ho, Eileen Cordoba Tongson, Ameth Aguirre, and Nancy Bouvier (Stanford University). J. S. K. performed the cellular immune assays with the assistance of Frank Ennis, MD, Laura Orphin, and John Cruz at the University of Massachusetts Medical School, and the authors acknowledge their support and assistance with ELISPOT and lymphoproliferation assays. VaxGen, Inc was the sponsor and created the protocol, obtained sites, and was responsible for the Investigational New Drug application and all reporting to the Food and Drug Administration. Each site had available board-certified cardiologists as well as other board-certified specialists to assist with any ocular, cutaneous, or neurological AEs; the authors appreciate their assistance. Financial support. This work was supported by VaxGen, Inc.
Potential conflicts of interest. R. N. G. was a principal site investigator for clinical trials sponsored by DynPort Vaccine Company LLC, Acambis PLC, VaxGen, Inc, and Bavarian-Nordic A/S. J. S. K. received funding from VaxGen, Inc and the National Institutes of Health (NIH; AI057319) for this study. K. M. E. received research funding from the NIH, CDC, and Novartis. C. L. S. received research funding from the NIH, CDC, and Sanofi Pasteur. At the time of the trial, M. G., J. K., C. E., and M. L. were employed by VaxGen, Inc. All other authors report no potential conflicts of interest.
ASJC Scopus subject areas
- Immunology and Allergy
- Infectious Diseases