Abstract
| Original language | English |
|---|---|
| Journal | Vaccine |
| Volume | 35 |
| Issue number | 42 |
| Pages (from-to) | 5629-5636 |
| ISSN | 0264-410X |
| DOIs | |
| Publication status | Published - 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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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 journal › Journal article › Research › peer-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
U2 - 10.1016/j.vaccine.2017.08.057
DO - 10.1016/j.vaccine.2017.08.057
M3 - Journal article
VL - 35
SP - 5629
EP - 5636
JO - Vaccine
JF - Vaccine
SN - 0264-410X
IS - 42
ER -