Differential requirements for T cells in viruslike particle- and rotavirus-induced protective immunity - PubMed (original) (raw)

Differential requirements for T cells in viruslike particle- and rotavirus-induced protective immunity

Sarah E Blutt et al. J Virol. 2008 Mar.

Abstract

Correlates of protection from rotavirus infection are controversial. We compared the roles of B and T lymphocytes in protective immunity induced either by intranasally administered nonreplicating viruslike particles or inactivated virus or by orally administered murine rotavirus. We found that protection induced by nonreplicating vaccines requires CD4(+) T cells and CD40/CD40L. In contrast, T cells were not required for short-term protective immunity induced by infection, but both T-cell-dependent and -independent mechanisms contributed to long-term maintenance of protection. Our findings indicate that more than one marker of protective immunity exists and that these markers depend on the vaccine that is administered.

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Figures

FIG. 1.

VLP-induced immunity against rotavirus infection is not maintained long-term. CD-1 mice were vaccinated intranasally with 2/6-VLPs (VLP) on days 0 and 14 or administered 105 50% infective doses (ID50) of ECwt (RV) on day 0. Mice were challenged on day 42 (short-term [ST]) or at 6 months (long-term [LT]) with 105 ID50 of ECwt, and the percentages of protection were assessed. The mean values for each group are indicated by the bars and the percentages (five mice per group). *, P < 0.05, compared to the results for the ST mice vaccinated with VLPs as determined by the Mann-Whitney U test; #, P < 0.05, compared to the results for the respective RV group as determined by the Mann-Whitney U test.

FIG. 2.

B cells contribute to the protective immunity induced by a live viral infection or by nonreplicating vaccines. (A) Wild-type BALB/c and B-cell-deficient JhD mice were vaccinated intranasally with 2/6-VLPs (VLP) or inactivated rotavirus (InV) on days 0 and 14 and challenged with 106 50% infective doses (ID50) of ECwt on day 42. Daily stool samples were analyzed by enzyme-linked immunosorbent assay for rotavirus antigen. The results are displayed as percentages of protection for the individual animals, and the mean values for each group are indicated by the bars and percentages (five mice per group). *, P < 0.05, compared to the results for the identically treated BALB/c mice as determined by the Mann-Whitney U test. (B) BALB/c and JhD mice were administered 106 ID50 of ECwt on day 0 and challenged with 106 ID50 of ECwt either on day 42 (short-term [ST]) or at 6 months (long-term [LT]). *, P < 0.05, compared to the results for the ST JhD mice as determined by the Mann-Whitney U test; #, P < 0.05, compared to the results shown in panel A for the VLP- or InV-vaccinated JhD−/− mice as determined by the Mann-Whitney U test.

FIG. 3.

T cells are essential for protection induced by nonreplicating vaccines but only contribute to protection induced by a live viral infection. (A) Wild-type C57BL/6 or TCRKO mice were vaccinated intranasally with 2/6-VLPs (VLP) or inactivated rotavirus (InV) on days 0 and 14 and challenged on day 42 with 103 50% infective doses (ID50) of ECwt. Daily stool samples were analyzed by enzyme-linked immunosorbent assay for rotavirus antigen. The results are displayed as percentages of protection for the individual animals, and the mean values for each group are indicated by the bars and percentages (five mice per group). *, P < 0.05, compared to the results for the identically treated C57BL/6 mice as determined by the Mann-Whitney U test. (B) C57BL/6 and TCRKO mice were administered 103 ID50 of ECwt on day 0 and challenged with 103 ID50 of ECwt either on day 42 (short-term [ST]) or at 6 months (long-term [LT]). *, P < 0.05, compared to the results for the ST TCRKO mice as determined by the Mann-Whitney U test.

FIG. 4.

T-cell-mediated protection induced by nonreplicating vaccines requires CD4 but not CD8 T cells. β2m−/−, CD4−/−, CD40−/−, and CD40L−/− mice were vaccinated with 2/6-VLPs (VLP) on days 0 and 14 or administered 103 50% infective doses (ID50) of ECwt (RV). The mice were challenged on day 42 with 103 ID50 of ECwt, and daily stool samples were analyzed by enzyme-linked immunosorbent assay for rotavirus antigen. The results are displayed as percentages of protection for the individual mice, and the bars and percentages indicate the means for each group (five mice per group). *, P < 0.05, compared to the results for the C57BL/6 mice shown in Fig. 3 as determined by the Mann-Whitney U test; #, P < 0.05, compared to the results for the respective strain administered ECwt as determined by the Mann-Whitney U test.

References

1. Bertolotti-Ciarlet, A., M. Ciarlet, S. E. Crawford, M. E. Conner, and M. K. Estes. 2003. Immunogenicity and protective efficacy of rotavirus 2/6-virus-like particles produced by a dual baculovirus expression vector and administered intramuscularly, intranasally, or orally to mice. Vaccine 213885-3900. -PubMed
1. Blutt, S. E., K. L. Warfield, D. E. Lewis, and M. E. Conner. 2002. Early response to rotavirus infection involves massive B cell activation. J. Immunol. 1685716-5721. -PubMed
1. Blutt, S. E., K. L. Warfield, C. M. O'Neal, M. K. Estes, and M. E. Conner. 2006. Host, viral, and vaccine factors that determine protective efficacy induced by rotavirus and virus-like particles (VLPs). Vaccine 241170-1179. -PubMed
1. Casola, A., M. K. Estes, S. E. Crawford, P. L. Ogra, P. B. Ernst, R. P. Garofalo, and S. E. Crowe. 1998. Rotavirus infection of cultured intestinal epithelial cells induces secretion of CXC and CC chemokines. Gastroenterology 114947-955. -PubMed
1. Choi, A. H.-C., M. Basu, M. M. McNeal, J. D. Clements, and R. L. Ward. 1999. Antibody-independent protection against rotavirus infection of mice stimulated by intranasal immunization with chimeric VP4 or VP6 protein. J. Virol. 737574-7581. -PMC -PubMed

Differential requirements for T cells in viruslike particle- and rotavirus-induced protective immunity - PubMed (original) (raw)