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Journal of Virology, May 2006, p. 4949-4961, Vol. 80, No. 10
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.10.4949-4961.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Mice Develop Effective but Delayed Protective Immune Responses When Immunized as Neonates either Intranasally with Nonliving VP6/LT(R192G) or Orally with Live Rhesus Rotavirus Vaccine Candidates

John L. VanCott,1 Anne E. Prada,1 Monica M. McNeal,1 Susan C. Stone,1 Mitali Basu,1 Bert Huffer Jr.,1 Kristi L. Smiley,1 Mingyuan Shao,2 Judy A. Bean,2 John D. Clements,3 Anthony H.-C. Choi,1 and Richard L. Ward1*

Divisions of Infectious Diseases,1 Biostatistics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229,2 Tulane University Medical Center, New Orleans, Louisiana 701123

Received 17 November 2005/ Accepted 25 February 2006

Rotavirus vaccines are delivered early in life, when the immune system is immature. To determine the effects of immaturity on responses to candidate vaccines, neonatal (7 days old) and adult mice were immunized with single doses of either Escherichia coli-expressed rotavirus VP6 protein and the adjuvant LT(R192G) or live rhesus rotavirus (RRV), and protection against fecal rotavirus shedding following challenge with the murine rotavirus strain EDIM was determined. Neonatal mice immunized intranasally with VP6/LT(R192G) were unprotected at 10 days postimmunization (dpi) and had no detectable rotavirus B-cell (antibody) or CD4+ CD8+ T-cell (rotavirus-inducible, Th1 [gamma interferon and interleukin-2 {IL-2}]-, Th2 [IL-5 and IL-4]-, or ThIL-17 [IL-17]-producing spleen cells) responses. However, by 28 and 42 dpi, these mice were significantly (P ≥ 0.003) protected and contained memory rotavirus-specific T cells but produced no rotavirus antibody. In contrast, adult mice were nearly fully protected by 10 dpi and contained both rotavirus immunoglobulin G and memory T cells. Neonates immunized orally with RRV were also less protected (P = 0.01) than adult mice by 10 dpi and produced correspondingly less rotavirus antibody. Both groups contained few rotavirus-specific memory T cells. Protection levels by 28 dpi for neonates or adults were equal, as were rotavirus antibody levels. This report introduces a neonatal mouse model for active protection studies with rotavirus vaccines. It indicates that, with time, neonatal mice develop full protection after intranasal immunization with VP6/LT(R192G) or oral immunization with a live heterologous rotavirus and supports reports that protection depends on CD4+ T cells or antibody, respectively.

* Corresponding author. Mailing address: Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH 45229. Phone: (513) 636-7628. Fax: (513) 636-7682. E-mail: dick.ward{at}cchmc.org.

Journal of Virology, May 2006, p. 4949-4961, Vol. 80, No. 10
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.10.4949-4961.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Jiang, J. Q., He, X.-S., Feng, N., Greenberg, H. B. (2008). Qualitative and Quantitative Characteristics of Rotavirus-Specific CD8 T Cells Vary Depending on the Route of Infection. J. Virol. 82: 6812-6819 [Abstract] [Full Text]  
  • Smiley, K. L., McNeal, M. M., Basu, M., Choi, A. H.-C., Clements, J. D., Ward, R. L. (2007). Association of Gamma Interferon and Interleukin-17 Production in Intestinal CD4+ T Cells with Protection against Rotavirus Shedding in Mice Intranasally Immunized with VP6 and the Adjuvant LT(R192G). J. Virol. 81: 3740-3748 [Abstract] [Full Text]  


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