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Science 5 April 1996:
Vol. 272. no. 5258, pp. 104 - 107
DOI: 10.1126/science.272.5258.104
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Reports

Protective Effect of Rotavirus VP6-Specific IgA Monoclonal Antibodies That Lack Neutralizing Activity

John W. Burns, Majid Siadat-Pajouh, Ajit A. Krishnaney, Harry B. Greenberg

Rotaviruses are the leading cause of severe gastroenteritis and dehydrating diarrhea in young children and animals worldwide. A murine model and ``backpack tumor'' transplantation were used to determine the protective effect of antibodies against VP4 (an outer capsid viral protein) and VP6 (a major inner capsid viral protein). Only two non-neutralizing immunoglobulin A (IgA) antibodies to VP6 were capable of preventing primary and resolving chronic murine rotavirus infections. These antibodies were not active, however, when presented directly to the luminal side of the intestinal tract. These findings support the hypothesis that in vivo intracellular viral inactivation by secretory IgA during transcytosis is a mechanism of host defense against rotavirus infection.

Departments of Medicine and Microbiology and Immunology, Medical School Lab Surge Building, Room P304, Stanford University School of Medicine, Stanford, CA 94305, and the Veterans Administration (VA), Palo Alto Health Care System, 3801 Miranda Avenue (154-C), Palo Alto, CA 94304, USA.


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A. Coste, J.-C. Sirard, K. Johansen, J. Cohen, and J.-P. Kraehenbuhl (2000)
J. Virol. 74, 8966-8971
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Protective Immunity to Rotavirus Shedding in the Absence of Interleukin-6: Th1 Cells and Immunoglobulin A Develop Normally.
J. L. VanCott, M. A. Franco, H. B. Greenberg, S. Sabbaj, B. Tang, R. Murray, and J. R. McGhee (2000)
J. Virol. 74, 5250-5256
   Abstract »    Full Text »    PDF »
VP7 and VP4 Genotyping of Human Group A Rotavirus in Buenos Aires, Argentina.
M. H. Arguelles, G. A. Villegas, A. Castello, A. Abrami, P. D. Ghiringhelli, L. Semorile, and G. Glikmann (2000)
J. Clin. Microbiol. 38, 252-259
   Abstract »    Full Text »    PDF »
Absence of Epithelial Immunoglobulin a Transport, with Increased Mucosal Leakiness, in Polymeric Immunoglobulin Receptor/Secretory Component-Deficient Mice.
F.-E. Johansen, M. Pekna, I. N. Norderhaug, B. Haneberg, M. A. Hietala, P. Krajci, C. Betsholtz, and P. Brandtzaeg (1999)
J. Exp. Med. 190, 915-922
   Abstract »    Full Text »    PDF »
Antibody-Independent Protection against Rotavirus Infection of Mice Stimulated by Intranasal Immunization with Chimeric VP4 or VP6 Protein.
A. H.-C. Choi, M. Basu, M. M. McNeal, J. D. Clements, and R. L. Ward (1999)
J. Virol. 73, 7574-7581
   Abstract »    Full Text »    PDF »
Gut as the Largest Immunologic Tissue.
I. Takahashi and H. Kiyono (1999)
JPEN J Parenter Enteral Nutr 23, S7-S12
   Abstract »    PDF »
Intranasal Antibody Prophylaxis for Protection against Viral Disease.
R. Weltzin and T. P. Monath (1999)
Clin. Microbiol. Rev. 12, 383-393
   Abstract »    Full Text »    PDF »
Targeted Deletion of the IgA Constant Region in Mice Leads to IgA Deficiency with Alterations in Expression of Other Ig Isotypes.
G. R. Harriman, M. Bogue, P. Rogers, M. Finegold, S. Pacheco, A. Bradley, Y. Zhang, and I. N. Mbawuike (1999)
J. Immunol. 162, 2521-2529
   Abstract »    Full Text »    PDF »
Mucosal Immunity to Influenza Without IgA: An IgA Knockout Mouse Model.
I. N. Mbawuike, S. Pacheco, C. L. Acuna, K. C. Switzer, Y. Zhang, and G. R. Harriman (1999)
J. Immunol. 162, 2530-2537
   Abstract »    Full Text »    PDF »
Serum Antitoxin Antibodies Mediate Systemic and Mucosal Protection from Clostridium difficile Disease in Hamsters.
P. J. Giannasca, Z.-x. Zhang, W.-d. Lei, J. A. Boden, M. A. Giel, T. P. Monath, and W. D. Thomas Jr. (1999)
Infect. Immun. 67, 527-538
   Abstract »    Full Text »    PDF »
The Memory B Cell Subset Responsible for the Secretory IgA Response and Protective Humoral Immunity to Rotavirus Expresses the Intestinal Homing Receptor, {alpha}4{beta}7.
M. B. Williams, J. R. Rose, L. S. Rott, M. A. Franco, H. B. Greenberg, and E. C. Butcher (1998)
J. Immunol. 161, 4227-4235
   Abstract »    Full Text »    PDF »
Role of Immunoglobulin A Monoclonal Antibodies against P23 in Controlling Murine Cryptosporidium parvum Infection.
F. J. Enriquez and M. W. Riggs (1998)
Infect. Immun. 66, 4469-4473
   Abstract »    Full Text »    PDF »
Crystallization and Preliminary X-Ray Analysis of Rotavirus Protein VP6.
I. Petitpas, J. Lepault, P. Vachette, A. Charpilienne, M. Mathieu, E. Kohli, P. Pothier, J. Cohen, and F. A. Rey (1998)
J. Virol. 72, 7615-7619
   Abstract »    Full Text »    PDF »
Protective Immunity Induced by Oral Immunization with a Rotavirus DNA Vaccine Encapsulated in Microparticles.
S. C. Chen, D. H. Jones, E. F. Fynan, G. H. Farrar, J. C. S. Clegg, H. B. Greenberg, and J. E. Herrmann (1998)
J. Virol. 72, 5757-5761
   Abstract »    Full Text »    PDF »
Antirotavirus Immunoglobulin A Neutralizes Virus In Vitro after Transcytosis through Epithelial Cells and Protects Infant Mice from Diarrhea.
F. M. Ruggeri, K. Johansen, G. Basile, J.-P. Kraehenbuhl, and L. Svensson (1998)
J. Virol. 72, 2708-2714
   Abstract »    Full Text »    PDF »
IV. How epithelial transport of IgA antibodies relates to host defense.
M. E. Lamm (1998)
Am J Physiol Gastrointest Liver Physiol 274, G614-G617
   Abstract »    Full Text »    PDF »
HIV-1 Neutralizing Antibodies in the Genital and Respiratory Tracts of Mice Intranasally Immunized with Oligomeric gp160.
T. C. VanCott, R. W. Kaminski, J. R. Mascola, V. S. Kalyanaraman, N. M. Wassef, C. R. Alving, J.T. Ulrich, G. H. Lowell, and D. L. Birx (1998)
J. Immunol. 160, 2000-2012
   Abstract »    Full Text »    PDF »
Antibody-Secreting Cell Responses and Protective Immunity Assessed in Gnotobiotic Pigs Inoculated Orally or Intramuscularly with Inactivated Human Rotavirus.
L. Yuan, S.-Y. Kang, L. A. Ward, T. L. To, and L. J. Saif (1998)
J. Virol. 72, 330-338
   Abstract »    Full Text »    PDF »


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