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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 tattooing induces long-lasting memory T cells. Mice that survived tumor challenge as depicted in Figure 3 were sacrificed on day 90 after tumor inoculation. Isolated spleen and inguinal lymph node cells were in vitro restimulated for seven days. Activity of restimulated spleen (a) and lymph node (b) cells were analyzed in regular and micro CTL assay, respectively. E:T ratio—effector:target ratio.
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vaccines-03-00221-f004: SFVeE6,7 tattooing induces long-lasting memory T cells. Mice that survived tumor challenge as depicted in Figure 3 were sacrificed on day 90 after tumor inoculation. Isolated spleen and inguinal lymph node cells were in vitro restimulated for seven days. Activity of restimulated spleen (a) and lymph node (b) cells were analyzed in regular and micro CTL assay, respectively. E:T ratio—effector:target ratio.

Mentions: We further investigated the potency of SFVeE6,7 tattooing in inducing long-lasting T cell responses. Mice that survived the tumor challenge (depicted in Figure 3) were sacrificed on day 90 after tumor inoculation. Isolated spleen and draining inguinal lymph node cells were in vitro restimulated for seven days. Activity of restimulated spleen and lymph node cells was tested in regular and micro-CTL assays, respectively. Splenocytes isolated from each surviving mouse were able to efficiently lyse target cells after in vitro restimulation (Figure 4a). No differences were observed in lytic activity of spleen cells obtained from tattooed or intramuscularly injected mice. Similar results were obtained with cells isolated from draining inguinal lymph nodes analyzed with the micro-CTL assay (Figure 4b). These results show that SFVeE6,7 delivered via tattoo injection results in the induction of long-lasting T cells in vivo.


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 tattooing induces long-lasting memory T cells. Mice that survived tumor challenge as depicted in Figure 3 were sacrificed on day 90 after tumor inoculation. Isolated spleen and inguinal lymph node cells were in vitro restimulated for seven days. Activity of restimulated spleen (a) and lymph node (b) cells were analyzed in regular and micro CTL assay, respectively. E:T ratio—effector:target ratio.
© Copyright Policy
Related In: Results  -  Collection

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

vaccines-03-00221-f004: SFVeE6,7 tattooing induces long-lasting memory T cells. Mice that survived tumor challenge as depicted in Figure 3 were sacrificed on day 90 after tumor inoculation. Isolated spleen and inguinal lymph node cells were in vitro restimulated for seven days. Activity of restimulated spleen (a) and lymph node (b) cells were analyzed in regular and micro CTL assay, respectively. E:T ratio—effector:target ratio.
Mentions: We further investigated the potency of SFVeE6,7 tattooing in inducing long-lasting T cell responses. Mice that survived the tumor challenge (depicted in Figure 3) were sacrificed on day 90 after tumor inoculation. Isolated spleen and draining inguinal lymph node cells were in vitro restimulated for seven days. Activity of restimulated spleen and lymph node cells was tested in regular and micro-CTL assays, respectively. Splenocytes isolated from each surviving mouse were able to efficiently lyse target cells after in vitro restimulation (Figure 4a). No differences were observed in lytic activity of spleen cells obtained from tattooed or intramuscularly injected mice. Similar results were obtained with cells isolated from draining inguinal lymph nodes analyzed with the micro-CTL assay (Figure 4b). These results show that SFVeE6,7 delivered via tattoo injection results in the induction of long-lasting T cells in vivo.

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