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Journal of Virology, August 2003, p. 8322-8328, Vol. 77, No. 15
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.15.8322-8328.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Virus-Neutralizing Activity Mediated by the Fab Fragment of a Hemagglutinin-Specific Antibody Is Sufficient for the Resolution of Influenza Virus Infection in SCID Mice

Krystyna Mozdzanowska, Jingqi Feng, and Walter Gerhard*

The Wistar Institute, Philadelphia, Pennsylvania 19104

Received 26 February 2003/ Accepted 13 May 2003

Antibodies (Abs) contribute to the control of influenza virus infection in vivo by reducing progeny virus yield from infected cells (yield reduction [YR]) and by inhibiting progeny virus from spreading the infection to new host cells (virus neutralization [VN]). Previous studies showed that the infection could be resolved in severe combined immunodeficiency (SCID) mice by treatment with hemagglutinin (HA)-specific monoclonal antibodies (MAbs) that exhibit both VN and YR activities but not by MAbs that exhibited only YR activity. To determine whether virus clearance requires both activities, we measured the therapeutic activity of an HA-specific MAb (VN and YR) and its Fab fragment (VN) by intranasal (i.n.) administration to infected SCID mice. Immunoglobulin G (IgG) and Fab cleared the infection with i.n. 50% effective doses (ED50s) of 16 and 90 pmol, respectively. To resolve an established infection solely by VN activity, Fab must be present in the respiratory tract at an effective threshold concentration until all infected cells have died and production of virus has ceased. Because IgG and Fab had different half-lives in the respiratory tract (22 and 8 h, respectively) and assuming that both operated mainly or solely by VN, it could be estimated that clearance was achieved 24 h after Ab treatment when both reagents were present in the respiratory tract at ~10 pmol. This dose was ~200 times larger than the respiratory tract-associated Ab dose resulting from administration of the intraperitoneal ED50 (270 pmol) of IgG. This indicated that our procedure of i.n. administration of Ab did not make optimal use of the Ab's therapeutic activity.

* Corresponding author. Mailing address: The Wistar Institute, 3601 Spruce St., Philadelphia, PA 19104. Phone: (215) 898-3840. Fax: (215) 898-3868. E-mail: gerhard{at}wistar.upenn.edu.

Journal of Virology, August 2003, p. 8322-8328, Vol. 77, No. 15
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.15.8322-8328.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Jayasekera, J. P., Moseman, E. A., Carroll, M. C. (2007). Natural Antibody and Complement Mediate Neutralization of Influenza Virus in the Absence of Prior Immunity. J. Virol. 81: 3487-3494 [Abstract] [Full Text]  
  • Zharikova, D., Mozdzanowska, K., Feng, J., Zhang, M., Gerhard, W. (2005). Influenza Type A Virus Escape Mutants Emerge In Vivo in the Presence of Antibodies to the Ectodomain of Matrix Protein 2. J. Virol. 79: 6644-6654 [Abstract] [Full Text]  


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