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Tattoo Delivery of a Semliki Forest Virus-Based Vaccine Encoding Human Papillomavirus E6 and E7.

van de Wall S, Walczak M, van Rooij N, Hoogeboom BN, Meijerhof T, Nijman HW, Daemen T - Vaccines (Basel) (2015)

Bottom Line: Tattoo injection of rSFV particles resulted in antigen expression in both the skin and draining lymph nodes.Strikingly, despite the observed lower overall transgene expression, SFVeE6,7 delivered via tattoo injection resulted in higher or equal levels of immune responses as compared to intramuscular injection.The intrinsic immunogenic potential of tattooing provides a benefit for immunotherapy based on an alphavirus.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, HPC EB88, PO Box 30.001, 9700 RB Groningen, The Netherlands. m.n.s.van.de.wall@umcg.nl.

ABSTRACT
The skin is an attractive organ for immunization because of the presence of antigen-presenting cells. Intradermal delivery via tattooing has demonstrated superior vaccine immunogenicity of DNA vaccines in comparison to conventional delivery methods. In this study, we explored the efficacy of tattoo injection of a tumor vaccine based on recombinant Semliki Forest virus replicon particles (rSFV) targeting human papillomavirus (HPV). Tattoo injection of rSFV particles resulted in antigen expression in both the skin and draining lymph nodes. In comparison with intramuscular injection, the overall antigen expression determined at the site of administration and draining lymph nodes was 10-fold lower upon tattoo injection. Delivery of SFV particles encoding the E6 and E7 antigens of human papillomavirus type 16 (SFVeE6,7) via tattooing resulted in HPV-specific cytotoxic T cells and in vivo therapeutic antitumor response. Strikingly, despite the observed lower overall transgene expression, SFVeE6,7 delivered via tattoo injection resulted in higher or equal levels of immune responses as compared to intramuscular injection. The intrinsic immunogenic potential of tattooing provides a benefit for immunotherapy based on an alphavirus.

No MeSH data available.


Related in: MedlinePlus

Tattooing of rSFV replicon particles results in high transgene expression. Luciferase expression by SFVLuc was determined in vivo with bioluminescence imaging using a CCD camera. Mice were tattooed (a) or injected intramuscularly (b) with 107 i.u. of SFVLuc. After 6 h, images with an integration time 30 s were taken. Blue colors represent the least and red colors represent the most intense light intensity. Two representative mice for each group are shown. Immediately after in vivo measurements, animals were sacrificed and muscles from the intramuscularly treated group or skin from the tattooed group and draining inguinal lymph nodes were isolated for ex vivo luciferase expression. Luciferase expression is shown as expression per mg organ (c) or per total organ (d) (n = 4). Data of a representative experiment out of two are shown. * p < 0.05. Mice were intramuscularly injected with 108 i.u. of SFV-EGFP (e) or PBS (f). After 24 h, skin and muscle from the site of administration were excised and analyzed by immunofluorescence staining. For immunofluorescent staining, muscle tissue expressing EGFP were analyzed using anti-GFP antibody (green). Cell nuclei were detected using DAPI (blue) (magnification 40×). A representative image for each group is shown.
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vaccines-03-00221-f001: Tattooing of rSFV replicon particles results in high transgene expression. Luciferase expression by SFVLuc was determined in vivo with bioluminescence imaging using a CCD camera. Mice were tattooed (a) or injected intramuscularly (b) with 107 i.u. of SFVLuc. After 6 h, images with an integration time 30 s were taken. Blue colors represent the least and red colors represent the most intense light intensity. Two representative mice for each group are shown. Immediately after in vivo measurements, animals were sacrificed and muscles from the intramuscularly treated group or skin from the tattooed group and draining inguinal lymph nodes were isolated for ex vivo luciferase expression. Luciferase expression is shown as expression per mg organ (c) or per total organ (d) (n = 4). Data of a representative experiment out of two are shown. * p < 0.05. Mice were intramuscularly injected with 108 i.u. of SFV-EGFP (e) or PBS (f). After 24 h, skin and muscle from the site of administration were excised and analyzed by immunofluorescence staining. For immunofluorescent staining, muscle tissue expressing EGFP were analyzed using anti-GFP antibody (green). Cell nuclei were detected using DAPI (blue) (magnification 40×). A representative image for each group is shown.

Mentions: To investigate the level of antigen expression upon rSFV administration, rSFV particles encoding firefly luciferase were used (SFVLuc). Mice were tattooed or intramuscularly injected with 107 i.u. of SFVLuc. Six hours after rSFV administration, in vivo luciferase expression was visualized using bioluminescence imaging. Interestingly, upon rSFV tattooing, luciferase was not only expressed in the tattooed skin but also in the draining inguinal lymph nodes (Figure 1a). In comparison, SFVLuc injected intramuscularly resulted mainly in luciferase expression in the injected muscle (Figure 1b).


Tattoo Delivery of a Semliki Forest Virus-Based Vaccine Encoding Human Papillomavirus E6 and E7.

van de Wall S, Walczak M, van Rooij N, Hoogeboom BN, Meijerhof T, Nijman HW, Daemen T - Vaccines (Basel) (2015)

Tattooing of rSFV replicon particles results in high transgene expression. Luciferase expression by SFVLuc was determined in vivo with bioluminescence imaging using a CCD camera. Mice were tattooed (a) or injected intramuscularly (b) with 107 i.u. of SFVLuc. After 6 h, images with an integration time 30 s were taken. Blue colors represent the least and red colors represent the most intense light intensity. Two representative mice for each group are shown. Immediately after in vivo measurements, animals were sacrificed and muscles from the intramuscularly treated group or skin from the tattooed group and draining inguinal lymph nodes were isolated for ex vivo luciferase expression. Luciferase expression is shown as expression per mg organ (c) or per total organ (d) (n = 4). Data of a representative experiment out of two are shown. * p < 0.05. Mice were intramuscularly injected with 108 i.u. of SFV-EGFP (e) or PBS (f). After 24 h, skin and muscle from the site of administration were excised and analyzed by immunofluorescence staining. For immunofluorescent staining, muscle tissue expressing EGFP were analyzed using anti-GFP antibody (green). Cell nuclei were detected using DAPI (blue) (magnification 40×). A representative image for each group is shown.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494346&req=5

vaccines-03-00221-f001: Tattooing of rSFV replicon particles results in high transgene expression. Luciferase expression by SFVLuc was determined in vivo with bioluminescence imaging using a CCD camera. Mice were tattooed (a) or injected intramuscularly (b) with 107 i.u. of SFVLuc. After 6 h, images with an integration time 30 s were taken. Blue colors represent the least and red colors represent the most intense light intensity. Two representative mice for each group are shown. Immediately after in vivo measurements, animals were sacrificed and muscles from the intramuscularly treated group or skin from the tattooed group and draining inguinal lymph nodes were isolated for ex vivo luciferase expression. Luciferase expression is shown as expression per mg organ (c) or per total organ (d) (n = 4). Data of a representative experiment out of two are shown. * p < 0.05. Mice were intramuscularly injected with 108 i.u. of SFV-EGFP (e) or PBS (f). After 24 h, skin and muscle from the site of administration were excised and analyzed by immunofluorescence staining. For immunofluorescent staining, muscle tissue expressing EGFP were analyzed using anti-GFP antibody (green). Cell nuclei were detected using DAPI (blue) (magnification 40×). A representative image for each group is shown.
Mentions: To investigate the level of antigen expression upon rSFV administration, rSFV particles encoding firefly luciferase were used (SFVLuc). Mice were tattooed or intramuscularly injected with 107 i.u. of SFVLuc. Six hours after rSFV administration, in vivo luciferase expression was visualized using bioluminescence imaging. Interestingly, upon rSFV tattooing, luciferase was not only expressed in the tattooed skin but also in the draining inguinal lymph nodes (Figure 1a). In comparison, SFVLuc injected intramuscularly resulted mainly in luciferase expression in the injected muscle (Figure 1b).

Bottom Line: Tattoo injection of rSFV particles resulted in antigen expression in both the skin and draining lymph nodes.Strikingly, despite the observed lower overall transgene expression, SFVeE6,7 delivered via tattoo injection resulted in higher or equal levels of immune responses as compared to intramuscular injection.The intrinsic immunogenic potential of tattooing provides a benefit for immunotherapy based on an alphavirus.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, HPC EB88, PO Box 30.001, 9700 RB Groningen, The Netherlands. m.n.s.van.de.wall@umcg.nl.

ABSTRACT
The skin is an attractive organ for immunization because of the presence of antigen-presenting cells. Intradermal delivery via tattooing has demonstrated superior vaccine immunogenicity of DNA vaccines in comparison to conventional delivery methods. In this study, we explored the efficacy of tattoo injection of a tumor vaccine based on recombinant Semliki Forest virus replicon particles (rSFV) targeting human papillomavirus (HPV). Tattoo injection of rSFV particles resulted in antigen expression in both the skin and draining lymph nodes. In comparison with intramuscular injection, the overall antigen expression determined at the site of administration and draining lymph nodes was 10-fold lower upon tattoo injection. Delivery of SFV particles encoding the E6 and E7 antigens of human papillomavirus type 16 (SFVeE6,7) via tattooing resulted in HPV-specific cytotoxic T cells and in vivo therapeutic antitumor response. Strikingly, despite the observed lower overall transgene expression, SFVeE6,7 delivered via tattoo injection resulted in higher or equal levels of immune responses as compared to intramuscular injection. The intrinsic immunogenic potential of tattooing provides a benefit for immunotherapy based on an alphavirus.

No MeSH data available.


Related in: MedlinePlus