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

Author:
Overgaard, Nana H., Frøsig, Thomas M., Jakobsen, Jeanne T., Buus, Søren, Andersen, Mads H., Jungersen, Gregers
Source:
Vaccine 2017 v.35 no.42 pp. 5629-5636
ISSN:
0264-410X
Subject:
T-lymphocytes, adjuvants, animal models, antigens, body size, cytotoxicity, humans, immune response, immunization, immunoglobulin G, intraperitoneal injection, miniature swine, swine, tetanus, vaccines
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.
Agid:
5831657