PLGA particle vaccination elicits resident memory CD8 T cells protecting from tumors and infection

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2022
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The essential role of tissue-resident memory T cells (TRM cells) in offering protection from recurring infections and malignant tumors is becoming increasingly clear. Due to their presence in many barrier tissues, TRM cells are ideally located to rapidly respond to re-encountered pathogens. Moreover, a host of studies has shown that the quantity of TRM cells correlates with increased survival rates in cancer patients. Therefore, vaccination strategies which induce a strong and sustained TRM cell response are particularly promising. In this study we show that this response can be induced by employing a prime-boost vaccination strategy using biodegradable poly (D,L-lactide-co-glycolide) microspheres (PLGA MS). A subcutaneous prime immunization followed by an intranasal boost immunization led to a strong TRM cell response in the lungs of mice 6 days after the boost vaccination. Although numbers subsequently declined, TRM cells were still detectable 60 days after vaccination. Functionally, we observed that immunized mice were protected from lung metastasis formation and tumor growth in a B16Bl6 melanoma model. Furthermore, the TRM cells induced by PLGA MS immunization provided protection in an infectious model using a recombinant influenza A virus (IAV). Taken together, these results show that the ability of PLGA MS to induce a strong TRM cell response further supports their use as a potent vaccine.

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ISO 690MACKERRACHER, Anna, Annette SOMMERSHOF, Marcus GRÖTTRUP, 2022. PLGA particle vaccination elicits resident memory CD8 T cells protecting from tumors and infection. In: European Journal of Pharmaceutical Sciences. Elsevier. 2022, 175, 106209. ISSN 0928-0987. eISSN 1879-0720. Available under: doi: 10.1016/j.ejps.2022.106209
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@article{MacKerracher2022-08parti-57574,
  year={2022},
  doi={10.1016/j.ejps.2022.106209},
  title={PLGA particle vaccination elicits resident memory CD8 T cells protecting from tumors and infection},
  volume={175},
  issn={0928-0987},
  journal={European Journal of Pharmaceutical Sciences},
  author={MacKerracher, Anna and Sommershof, Annette and Gröttrup, Marcus},
  note={Article Number: 106209}
}
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    <dcterms:abstract xml:lang="eng">The essential role of tissue-resident memory T cells (T&lt;sub&gt;RM&lt;/sub&gt; cells) in offering protection from recurring infections and malignant tumors is becoming increasingly clear. Due to their presence in many barrier tissues, T&lt;sub&gt;RM&lt;/sub&gt; cells are ideally located to rapidly respond to re-encountered pathogens. Moreover, a host of studies has shown that the quantity of T&lt;sub&gt;RM&lt;/sub&gt; cells correlates with increased survival rates in cancer patients. Therefore, vaccination strategies which induce a strong and sustained T&lt;sub&gt;RM&lt;/sub&gt; cell response are particularly promising. In this study we show that this response can be induced by employing a prime-boost vaccination strategy using biodegradable poly (D,L-lactide-co-glycolide) microspheres (PLGA MS). A subcutaneous prime immunization followed by an intranasal boost immunization led to a strong T&lt;sub&gt;RM&lt;/sub&gt; cell response in the lungs of mice 6 days after the boost vaccination. Although numbers subsequently declined, T&lt;sub&gt;RM&lt;/sub&gt; cells were still detectable 60 days after vaccination. Functionally, we observed that immunized mice were protected from lung metastasis formation and tumor growth in a B16Bl6 melanoma model. Furthermore, the T&lt;sub&gt;RM&lt;/sub&gt; cells induced by PLGA MS immunization provided protection in an infectious model using a recombinant influenza A virus (IAV). Taken together, these results show that the ability of PLGA MS to induce a strong T&lt;sub&gt;RM&lt;/sub&gt; cell response further supports their use as a potent vaccine.</dcterms:abstract>
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