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Robust intrapulmonary CD8 T cell responses and protection with an attenuated N1L deleted vaccinia virus.

Mathew A, O'Bryan J, Marshall W, Kotwal GJ, Terajima M, Green S, Rothman AL, Ennis FA - PLoS ONE (2008)

Bottom Line: Vaccinia viruses have been used as a model for viral disease and as a protective live vaccine.Infection by the intranasal, intraperitoneal, and tail scarification routes resulted in the robust induction of cytolytic virus-specific CD8 T cells in the spleens and the lungs.These results indicate that the attenuated vGK5 virus protects against subsequent infection and suggest that the N1L protein limits the strength of the early antiviral CD8 T cell response following respiratory infection.

View Article: PubMed Central - PubMed

Affiliation: Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, Massachusetts, USA. anuja.mathew@umassmed.edu

ABSTRACT

Background: Vaccinia viruses have been used as a model for viral disease and as a protective live vaccine.

Methodology and principal findings: We investigated the immunogenicity of an attenuated strain of vaccinia virus engineered to inactivate the N1L gene (vGK5). Using the intranasal route, this recombinant virus was 2 logs less virulent compared to the wildtype VACV-WR. Infection by the intranasal, intraperitoneal, and tail scarification routes resulted in the robust induction of cytolytic virus-specific CD8 T cells in the spleens and the lungs. VACV-specific antibodies were also detected in the sera of mice infected 3-5 months prior with the attenuated vGK5 virus. Finally, mice immunized with vGK5 were significantly protected when challenged with a lethal dose of VACV-WR.

Conclusions: These results indicate that the attenuated vGK5 virus protects against subsequent infection and suggest that the N1L protein limits the strength of the early antiviral CD8 T cell response following respiratory infection.

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Related in: MedlinePlus

Viral titers following i.n. infections.(A) Spleens and (B) lungs (n = 4–8 per group) were harvested on day 7 from mice infected with VACV-WR and vGK5 by the i.n. route. VACV titers were determined and expressed as log10 PFU per gram of lung and spleen tissue. – represents median values of titers in respective organs. N.S. = not significant. Each symbol represents the titer obtained in target organs of individual mice; median values are denoted by horizontal lines. P values were determined by Student's t test.
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pone-0003323-g005: Viral titers following i.n. infections.(A) Spleens and (B) lungs (n = 4–8 per group) were harvested on day 7 from mice infected with VACV-WR and vGK5 by the i.n. route. VACV titers were determined and expressed as log10 PFU per gram of lung and spleen tissue. – represents median values of titers in respective organs. N.S. = not significant. Each symbol represents the titer obtained in target organs of individual mice; median values are denoted by horizontal lines. P values were determined by Student's t test.

Mentions: Since the timing of antigen exposure has been shown to influence the magnitude and quality of the CD8+ T cell response, we examined viral replication in multiple organs including the spleens, lungs and ovaries of mice infected by the i.n. and i.p. route. 7 days post infection, viral titers were low but detectible in the spleens of mice infected with 106, 104.5 and 103.5 vGK5 by the i.n. route (Fig. 5A) and titers were several logs higher in the lungs of these mice at the same time point (Fig. 5B). Viral titers were 3–4 logs higher in the lungs of mice administered 103.5 VACV-WR compared to lungs of mice administered 103.5 vGK5 (Fig. 5B). Equivalent viral loads were achieved in the lungs of mice infected with 104.5 PFU of vGK5 and 103.5 VACV-WR 7 days post infection. On day 5, mice that were infected via the i.p. route with both viruses had similar titers of virus in the ovaries, lungs and spleens (Fig. 4D). By day 7, virus was cleared from both the lungs and spleens of mice infected by the i.p. route while titers in the ovaries were detectible but at similar levels (data not shown).


Robust intrapulmonary CD8 T cell responses and protection with an attenuated N1L deleted vaccinia virus.

Mathew A, O'Bryan J, Marshall W, Kotwal GJ, Terajima M, Green S, Rothman AL, Ennis FA - PLoS ONE (2008)

Viral titers following i.n. infections.(A) Spleens and (B) lungs (n = 4–8 per group) were harvested on day 7 from mice infected with VACV-WR and vGK5 by the i.n. route. VACV titers were determined and expressed as log10 PFU per gram of lung and spleen tissue. – represents median values of titers in respective organs. N.S. = not significant. Each symbol represents the titer obtained in target organs of individual mice; median values are denoted by horizontal lines. P values were determined by Student's t test.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2553181&req=5

pone-0003323-g005: Viral titers following i.n. infections.(A) Spleens and (B) lungs (n = 4–8 per group) were harvested on day 7 from mice infected with VACV-WR and vGK5 by the i.n. route. VACV titers were determined and expressed as log10 PFU per gram of lung and spleen tissue. – represents median values of titers in respective organs. N.S. = not significant. Each symbol represents the titer obtained in target organs of individual mice; median values are denoted by horizontal lines. P values were determined by Student's t test.
Mentions: Since the timing of antigen exposure has been shown to influence the magnitude and quality of the CD8+ T cell response, we examined viral replication in multiple organs including the spleens, lungs and ovaries of mice infected by the i.n. and i.p. route. 7 days post infection, viral titers were low but detectible in the spleens of mice infected with 106, 104.5 and 103.5 vGK5 by the i.n. route (Fig. 5A) and titers were several logs higher in the lungs of these mice at the same time point (Fig. 5B). Viral titers were 3–4 logs higher in the lungs of mice administered 103.5 VACV-WR compared to lungs of mice administered 103.5 vGK5 (Fig. 5B). Equivalent viral loads were achieved in the lungs of mice infected with 104.5 PFU of vGK5 and 103.5 VACV-WR 7 days post infection. On day 5, mice that were infected via the i.p. route with both viruses had similar titers of virus in the ovaries, lungs and spleens (Fig. 4D). By day 7, virus was cleared from both the lungs and spleens of mice infected by the i.p. route while titers in the ovaries were detectible but at similar levels (data not shown).

Bottom Line: Vaccinia viruses have been used as a model for viral disease and as a protective live vaccine.Infection by the intranasal, intraperitoneal, and tail scarification routes resulted in the robust induction of cytolytic virus-specific CD8 T cells in the spleens and the lungs.These results indicate that the attenuated vGK5 virus protects against subsequent infection and suggest that the N1L protein limits the strength of the early antiviral CD8 T cell response following respiratory infection.

View Article: PubMed Central - PubMed

Affiliation: Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, Massachusetts, USA. anuja.mathew@umassmed.edu

ABSTRACT

Background: Vaccinia viruses have been used as a model for viral disease and as a protective live vaccine.

Methodology and principal findings: We investigated the immunogenicity of an attenuated strain of vaccinia virus engineered to inactivate the N1L gene (vGK5). Using the intranasal route, this recombinant virus was 2 logs less virulent compared to the wildtype VACV-WR. Infection by the intranasal, intraperitoneal, and tail scarification routes resulted in the robust induction of cytolytic virus-specific CD8 T cells in the spleens and the lungs. VACV-specific antibodies were also detected in the sera of mice infected 3-5 months prior with the attenuated vGK5 virus. Finally, mice immunized with vGK5 were significantly protected when challenged with a lethal dose of VACV-WR.

Conclusions: These results indicate that the attenuated vGK5 virus protects against subsequent infection and suggest that the N1L protein limits the strength of the early antiviral CD8 T cell response following respiratory infection.

Show MeSH
Related in: MedlinePlus