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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

SFVeE6,7 tattoo immunizations result in high therapeutic efficacy. Mice were inoculated subcutaneously with 2 × 104 TC-1 cells and 7 days later animals were tattoo- or intramuscularly immunized with 105 (low dose) or 5 × 106 (high dose) i.u. of SFVeE6,7 or injected with PBS. The mice were boosted twice with a one-week interval (day 14 and 21), using the same route of immunization. Tumor development was monitored twice weekly. When the tumor reached a volume of 1000 mm3, the mice were sacrificed. The effect of the immunization is depicted as the percentage of surviving mice. n = 7. * p < 0.05 as compared with PBS control group.
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vaccines-03-00221-f003: SFVeE6,7 tattoo immunizations result in high therapeutic efficacy. Mice were inoculated subcutaneously with 2 × 104 TC-1 cells and 7 days later animals were tattoo- or intramuscularly immunized with 105 (low dose) or 5 × 106 (high dose) i.u. of SFVeE6,7 or injected with PBS. The mice were boosted twice with a one-week interval (day 14 and 21), using the same route of immunization. Tumor development was monitored twice weekly. When the tumor reached a volume of 1000 mm3, the mice were sacrificed. The effect of the immunization is depicted as the percentage of surviving mice. n = 7. * p < 0.05 as compared with PBS control group.

Mentions: We analyzed anti-tumor therapeutic efficacy of SFVeE6,7 delivered via tattoo immunizations. Seven days after tumor inoculation mice were primed with 105 or 5 × 106 i.u. of SFVeE6,7 administered by tattooing or intramuscular injection. Mice were boosted twice, with a one-week interval using the same delivery route (day 14 and 21). Control mice developed tumors and had to be killed within 29 days after tumor inoculation (Figure 3). All SFVeE6,7 immunization protocols resulted in delayed tumor growth when compared to the control treatment (p < 0.05). In the groups immunized with 5 × 106 i.u. of SFVeE6,7 via tattooing or intramuscular injections, almost all mice were tumor-free on day 90 after tumor inoculation. SFVeE6,7 immunization with a dose of 105 i.u. resulted, as expected, in a lower therapeutic effect compared to 5 × 106 i.u. of SFVeE6,7 particles with both immunization routes. These data indicate that immunization with SFVeE6,7 delivered via tattoo injection results in the induction of a potent therapeutic antitumor response.


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)

SFVeE6,7 tattoo immunizations result in high therapeutic efficacy. Mice were inoculated subcutaneously with 2 × 104 TC-1 cells and 7 days later animals were tattoo- or intramuscularly immunized with 105 (low dose) or 5 × 106 (high dose) i.u. of SFVeE6,7 or injected with PBS. The mice were boosted twice with a one-week interval (day 14 and 21), using the same route of immunization. Tumor development was monitored twice weekly. When the tumor reached a volume of 1000 mm3, the mice were sacrificed. The effect of the immunization is depicted as the percentage of surviving mice. n = 7. * p < 0.05 as compared with PBS control group.
© Copyright Policy
Related In: Results  -  Collection

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

vaccines-03-00221-f003: SFVeE6,7 tattoo immunizations result in high therapeutic efficacy. Mice were inoculated subcutaneously with 2 × 104 TC-1 cells and 7 days later animals were tattoo- or intramuscularly immunized with 105 (low dose) or 5 × 106 (high dose) i.u. of SFVeE6,7 or injected with PBS. The mice were boosted twice with a one-week interval (day 14 and 21), using the same route of immunization. Tumor development was monitored twice weekly. When the tumor reached a volume of 1000 mm3, the mice were sacrificed. The effect of the immunization is depicted as the percentage of surviving mice. n = 7. * p < 0.05 as compared with PBS control group.
Mentions: We analyzed anti-tumor therapeutic efficacy of SFVeE6,7 delivered via tattoo immunizations. Seven days after tumor inoculation mice were primed with 105 or 5 × 106 i.u. of SFVeE6,7 administered by tattooing or intramuscular injection. Mice were boosted twice, with a one-week interval using the same delivery route (day 14 and 21). Control mice developed tumors and had to be killed within 29 days after tumor inoculation (Figure 3). All SFVeE6,7 immunization protocols resulted in delayed tumor growth when compared to the control treatment (p < 0.05). In the groups immunized with 5 × 106 i.u. of SFVeE6,7 via tattooing or intramuscular injections, almost all mice were tumor-free on day 90 after tumor inoculation. SFVeE6,7 immunization with a dose of 105 i.u. resulted, as expected, in a lower therapeutic effect compared to 5 × 106 i.u. of SFVeE6,7 particles with both immunization routes. These data indicate that immunization with SFVeE6,7 delivered via tattoo injection results in the induction of a potent therapeutic antitumor response.

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