Low antigen dose formulated in CAF09 adjuvant Favours a cytotoxic T-cell response following intraperitoneal immunization in Göttingen minipigs

Nana Haahr Overgaard, Thomas Mørch Frøsig, Jeanne Toft Jakobsen, Søren Buus, Mads Hald Andersen, Gregers Jungersen

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Abstract

The relationship between the antigen dose and the quality of an immune response generated upon immunization is poorly understood. However, findings show that the immune system is indeed influenced by the antigen dose; hence underlining the importance of correctly determining which dose to use in order to generate a certain type of immune response. To investigate this area further, we used Göttingen minipigs asan animal model especially due to the similar body size and high degree of immunome similarity between humans and pigs. In this study, we show that both a humoral and a cell-mediated immune (CMI) response can be generated following intraperitoneal immunization with tetanus toxoid (TT) formulated in the CAF09 liposomal adjuvant. Importantly, a low antigen dose induced more TT-specific polyfunctional T cells, whereas antigen-specific IgG production was observed upon high-dose immunization. Independent of antigen dose, intraperitoneal administration of antigen increased the amount of TT-specific cytotoxic CD8β+ T cells within the cytokine-producing T-cell pool when compared to the non-cytokine producing T-cell compartment. Taken together, these results demonstrate that a full protein formulated in the CAF09 adjuvant and administered to pigs via the intraperitoneal route effectively generates a cytotoxic T-cell response. Moreover, we confirm the inverse relationship between the antigen dose and the induction of polyfunctional T cells in a large animal model. These finding can have implications for the design of upcoming vaccine trials aiming at establishing a cytotoxic T-cell response.
Original languageEnglish
JournalVaccine
Volume35
Issue number42
Pages (from-to)5629-5636
ISSN0264-410X
DOIs
Publication statusPublished - 2017

Bibliographical note

This is an open access article under the CC BY-NC-ND license.

Keywords

  • Administration route
  • Antibody responses
  • Antigen dose
  • Cytokine production
  • Cytotoxic T cells
  • Immunization

Cite this

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title = "Low antigen dose formulated in CAF09 adjuvant Favours a cytotoxic T-cell response following intraperitoneal immunization in G{\"o}ttingen minipigs",
abstract = "The relationship between the antigen dose and the quality of an immune response generated upon immunization is poorly understood. However, findings show that the immune system is indeed influenced by the antigen dose; hence underlining the importance of correctly determining which dose to use in order to generate a certain type of immune response. To investigate this area further, we used G{\"o}ttingen minipigs asan animal model especially due to the similar body size and high degree of immunome similarity between humans and pigs. In this study, we show that both a humoral and a cell-mediated immune (CMI) response can be generated following intraperitoneal immunization with tetanus toxoid (TT) formulated in the CAF09 liposomal adjuvant. Importantly, a low antigen dose induced more TT-specific polyfunctional T cells, whereas antigen-specific IgG production was observed upon high-dose immunization. Independent of antigen dose, intraperitoneal administration of antigen increased the amount of TT-specific cytotoxic CD8β+ T cells within the cytokine-producing T-cell pool when compared to the non-cytokine producing T-cell compartment. Taken together, these results demonstrate that a full protein formulated in the CAF09 adjuvant and administered to pigs via the intraperitoneal route effectively generates a cytotoxic T-cell response. Moreover, we confirm the inverse relationship between the antigen dose and the induction of polyfunctional T cells in a large animal model. These finding can have implications for the design of upcoming vaccine trials aiming at establishing a cytotoxic T-cell response.",
keywords = "Administration route, Antibody responses, Antigen dose, Cytokine production, Cytotoxic T cells, Immunization",
author = "Overgaard, {Nana Haahr} and Fr{\o}sig, {Thomas M{\o}rch} and Jakobsen, {Jeanne Toft} and S{\o}ren Buus and Andersen, {Mads Hald} and Gregers Jungersen",
note = "This is an open access article under the CC BY-NC-ND license.",
year = "2017",
doi = "10.1016/j.vaccine.2017.08.057",
language = "English",
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Low antigen dose formulated in CAF09 adjuvant Favours a cytotoxic T-cell response following intraperitoneal immunization in Göttingen minipigs. / Overgaard, Nana Haahr; Frøsig, Thomas Mørch; Jakobsen, Jeanne Toft; Buus, Søren; Andersen, Mads Hald; Jungersen, Gregers.

In: Vaccine, Vol. 35, No. 42, 2017, p. 5629-5636.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Low antigen dose formulated in CAF09 adjuvant Favours a cytotoxic T-cell response following intraperitoneal immunization in Göttingen minipigs

AU - Overgaard, Nana Haahr

AU - Frøsig, Thomas Mørch

AU - Jakobsen, Jeanne Toft

AU - Buus, Søren

AU - Andersen, Mads Hald

AU - Jungersen, Gregers

N1 - This is an open access article under the CC BY-NC-ND license.

PY - 2017

Y1 - 2017

N2 - The relationship between the antigen dose and the quality of an immune response generated upon immunization is poorly understood. However, findings show that the immune system is indeed influenced by the antigen dose; hence underlining the importance of correctly determining which dose to use in order to generate a certain type of immune response. To investigate this area further, we used Göttingen minipigs asan animal model especially due to the similar body size and high degree of immunome similarity between humans and pigs. In this study, we show that both a humoral and a cell-mediated immune (CMI) response can be generated following intraperitoneal immunization with tetanus toxoid (TT) formulated in the CAF09 liposomal adjuvant. Importantly, a low antigen dose induced more TT-specific polyfunctional T cells, whereas antigen-specific IgG production was observed upon high-dose immunization. Independent of antigen dose, intraperitoneal administration of antigen increased the amount of TT-specific cytotoxic CD8β+ T cells within the cytokine-producing T-cell pool when compared to the non-cytokine producing T-cell compartment. Taken together, these results demonstrate that a full protein formulated in the CAF09 adjuvant and administered to pigs via the intraperitoneal route effectively generates a cytotoxic T-cell response. Moreover, we confirm the inverse relationship between the antigen dose and the induction of polyfunctional T cells in a large animal model. These finding can have implications for the design of upcoming vaccine trials aiming at establishing a cytotoxic T-cell response.

AB - The relationship between the antigen dose and the quality of an immune response generated upon immunization is poorly understood. However, findings show that the immune system is indeed influenced by the antigen dose; hence underlining the importance of correctly determining which dose to use in order to generate a certain type of immune response. To investigate this area further, we used Göttingen minipigs asan animal model especially due to the similar body size and high degree of immunome similarity between humans and pigs. In this study, we show that both a humoral and a cell-mediated immune (CMI) response can be generated following intraperitoneal immunization with tetanus toxoid (TT) formulated in the CAF09 liposomal adjuvant. Importantly, a low antigen dose induced more TT-specific polyfunctional T cells, whereas antigen-specific IgG production was observed upon high-dose immunization. Independent of antigen dose, intraperitoneal administration of antigen increased the amount of TT-specific cytotoxic CD8β+ T cells within the cytokine-producing T-cell pool when compared to the non-cytokine producing T-cell compartment. Taken together, these results demonstrate that a full protein formulated in the CAF09 adjuvant and administered to pigs via the intraperitoneal route effectively generates a cytotoxic T-cell response. Moreover, we confirm the inverse relationship between the antigen dose and the induction of polyfunctional T cells in a large animal model. These finding can have implications for the design of upcoming vaccine trials aiming at establishing a cytotoxic T-cell response.

KW - Administration route

KW - Antibody responses

KW - Antigen dose

KW - Cytokine production

KW - Cytotoxic T cells

KW - Immunization

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DO - 10.1016/j.vaccine.2017.08.057

M3 - Journal article

VL - 35

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JO - Vaccine

JF - Vaccine

SN - 0264-410X

IS - 42

ER -