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Journal of Virology, November 2005, p. 13454-13462, Vol. 79, No. 21
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.21.13454-13462.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Combinations of Polyclonal or Monoclonal Antibodies to Proteins of the Outer Membranes of the Two Infectious Forms of Vaccinia Virus Protect Mice against a Lethal Respiratory Challenge

Shlomo Lustig ,1,{dagger},{ddagger} Christiana Fogg,1,{dagger} J. Charles Whitbeck,2 Roselyn J. Eisenberg,2 Gary H. Cohen,2 and Bernard Moss1*

Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland,1 Schools of Dental and Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania2

Received 6 July 2005/ Accepted 2 August 2005

Previous studies demonstrated that antibodies to live vaccinia virus infection are needed for optimal protection against orthopoxvirus infection. The present report is the first to compare the protective abilities of individual and combinations of specific polyclonal and monoclonal antibodies that target proteins of the intracellular (IMV) and extracellular (EV) forms of vaccinia virus. The antibodies were directed to one IMV membrane protein, L1, and to two outer EV membrane proteins, A33 and B5. In vitro studies showed that the antibodies to L1 neutralized IMV and that the antibodies to A33 and B5 prevented the spread of EV in liquid medium. Prophylactic administration of individual antibodies to BALB/c mice partially protected them against disease following intranasal challenge with lethal doses of vaccinia virus. Combinations of antibodies, particularly anti-L1 and -A33 or -L1 and -B5, provided enhanced protection when administered 1 day before or 2 days after challenge. Furthermore, the protection was superior to that achieved with pooled immune gamma globulin from human volunteers inoculated with live vaccinia virus. In addition, single injections of anti-L1 plus anti-A33 antibodies greatly delayed the deaths of severe combined immunodeficiency mice challenged with vaccinia virus. These studies suggest that antibodies to two or three viral membrane proteins optimally derived from the outer membranes of IMV and EV, may be beneficial for prophylaxis or therapy of orthopoxvirus infections.

* Corresponding author. Mailing address: Laboratory of Viral Diseases, National Institutes of Health, 4 Memorial Dr., MSC 0445, Bethesda, MD 20892-0445. Phone: (301) 496-9869. Fax: (301) 480-1147. E-mail: bmoss{at}nih.gov.

{dagger} S.L. and C.F. contributed equally to this work.

{ddagger} Present address: Department of Infectious Diseases, Israel Institute for Biological Research, P.O. Box 19, 74100 Ness-Ziona, Israel.

Journal of Virology, November 2005, p. 13454-13462, Vol. 79, No. 21
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.21.13454-13462.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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