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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

Mice immunized with vGK5 are protected from a lethal challenge with VACV-WR.Mice were infected with 104.5, 106 PFU of vGK5 (n = 3/group) by the intranasal route. 1 month later immunized mice and age matched naïve controls were challenged with a lethal dose of VACV-WR (106 PFU) by the i.n. route. (A) Weights of mice were monitored over 5 days. Viral titers were measured in the (B) lungs and (C) ovaries and expressed as viral titers/gm lung tissue or ovaries. Each symbol represents the titer obtained in target organs of individual mice.
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pone-0003323-g006: Mice immunized with vGK5 are protected from a lethal challenge with VACV-WR.Mice were infected with 104.5, 106 PFU of vGK5 (n = 3/group) by the intranasal route. 1 month later immunized mice and age matched naïve controls were challenged with a lethal dose of VACV-WR (106 PFU) by the i.n. route. (A) Weights of mice were monitored over 5 days. Viral titers were measured in the (B) lungs and (C) ovaries and expressed as viral titers/gm lung tissue or ovaries. Each symbol represents the titer obtained in target organs of individual mice.

Mentions: Finally, to determine whether vGK5 infected mice were protected from a lethal challenge with the neurovirulent VACV-WR, mice that were immunized with 104.5 and 106 PFU of vGK5 intranasally 1 month earlier were challenged with 106 PFU of VACV-WR by the i.n. route. Mice were monitored for weight loss for 5 days and organs were isolated to measure viral load in naïve and immunized mice. While naïve mice rapidly lost weight and appeared moribund on d5, mice immunized with both doses of vGK5 did not lose significant weight (Fig. 6A). Viral titers at day 5 post challenge were significantly reduced in the lungs (Fig. 6B) and ovaries (Fig. 6C) of mice immunized with 106 and 104.5 of vGK5 compared to unimmunized groups.


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)

Mice immunized with vGK5 are protected from a lethal challenge with VACV-WR.Mice were infected with 104.5, 106 PFU of vGK5 (n = 3/group) by the intranasal route. 1 month later immunized mice and age matched naïve controls were challenged with a lethal dose of VACV-WR (106 PFU) by the i.n. route. (A) Weights of mice were monitored over 5 days. Viral titers were measured in the (B) lungs and (C) ovaries and expressed as viral titers/gm lung tissue or ovaries. Each symbol represents the titer obtained in target organs of individual mice.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2553181&req=5

pone-0003323-g006: Mice immunized with vGK5 are protected from a lethal challenge with VACV-WR.Mice were infected with 104.5, 106 PFU of vGK5 (n = 3/group) by the intranasal route. 1 month later immunized mice and age matched naïve controls were challenged with a lethal dose of VACV-WR (106 PFU) by the i.n. route. (A) Weights of mice were monitored over 5 days. Viral titers were measured in the (B) lungs and (C) ovaries and expressed as viral titers/gm lung tissue or ovaries. Each symbol represents the titer obtained in target organs of individual mice.
Mentions: Finally, to determine whether vGK5 infected mice were protected from a lethal challenge with the neurovirulent VACV-WR, mice that were immunized with 104.5 and 106 PFU of vGK5 intranasally 1 month earlier were challenged with 106 PFU of VACV-WR by the i.n. route. Mice were monitored for weight loss for 5 days and organs were isolated to measure viral load in naïve and immunized mice. While naïve mice rapidly lost weight and appeared moribund on d5, mice immunized with both doses of vGK5 did not lose significant weight (Fig. 6A). Viral titers at day 5 post challenge were significantly reduced in the lungs (Fig. 6B) and ovaries (Fig. 6C) of mice immunized with 106 and 104.5 of vGK5 compared to unimmunized groups.

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