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Journal of Virology, August 2008, p. 8022-8029, Vol. 82, No. 16
0022-538X/08/$08.00+0     doi:10.1128/JVI.00568-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Disparity between Levels of In Vitro Neutralization of Vaccinia Virus by Antibody to the A27 Protein and Protection of Mice against Intranasal Challenge{triangledown}

Christiana N. Fogg ,1,§,{dagger} Jeffrey L. Americo,1,§ Patricia L. Earl,1 Wolfgang Resch,1,{ddagger} Lydia Aldaz-Carroll,2 Roselyn J. Eisenberg,2 Gary H. Cohen,2 and Bernard Moss1*

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

Received 13 March 2008/ Accepted 23 May 2008

Immunization with recombinant proteins may provide a safer alternative to live vaccinia virus for prophylaxis of poxvirus infections. Although antibody protects against vaccinia virus infection, the mechanism is not understood and the selection of immunogens is daunting as there are dozens of surface proteins and two infectious forms known as the mature virion (MV) and the enveloped virion (EV). Our previous studies showed that mice immunized with soluble forms of EV membrane proteins A33 and B5 and MV membrane protein L1 or passively immunized with antibodies to these proteins survived an intranasal challenge with vaccinia virus. The present study compared MV protein A27, which has a role in virus attachment to glycosaminoglycans on the cell surface, to L1 with respect to immunogenicity and protection. Although mice developed similar levels of neutralizing antibody after immunizations with A27 or L1, A27-immunized mice exhibited more severe disease upon an intranasal challenge with vaccinia virus. In addition, mice immunized with A27 and A33 were not as well protected as mice receiving L1 and A33. Polyclonal rabbit anti-A27 and anti-L1 IgG had equivalent MV-neutralizing activities when measured by the prevention of infection of human or mouse cells or cells deficient in glycosaminoglycans or by adding antibody prior to or after virus adsorption. Nevertheless, the passive administration of antibody to A27 was poorly protective compared to the antibody to L1. These studies raise questions regarding the basis for antibody protection against poxvirus disease and highlight the importance of animal models for the early evaluation of vaccine candidates.

* Corresponding author. Mailing address: 33 North Drive MSC3210, Building 33, Room 1E13C.1, NIAID, NIH, Bethesda, MD 20892-3210. Phone: (301) 496-9869. Fax: (301) 480-1535. E-mail: bmoss{at}nih.gov

{triangledown} Published ahead of print on 4 June 2008.

§ Contributed equally to the study.

{dagger} Present address: Laboratory of Malaria and Vector Research, NIAID, NIH, 12735 Twinbrook Parkway, Twinbrook 3, Rockville, MD 20852.

{ddagger} Present address: National Center for Biotechnology Information, National Library of Medicine, NIH, 45 Center Drive, Bethesda, MD 20892-6510.

Journal of Virology, August 2008, p. 8022-8029, Vol. 82, No. 16
0022-538X/08/$08.00+0     doi:10.1128/JVI.00568-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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  • Howard, A. R., Senkevich, T. G., Moss, B. (2008). Vaccinia Virus A26 and A27 Proteins Form a Stable Complex Tethered to Mature Virions by Association with the A17 Transmembrane Protein. J. Virol. 82: 12384-12391 [Abstract] [Full Text]  


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