Intramuscular priming and intranasal boosting induce strong genital immunity through secretory IgA in minipigs infected with Chlamydia trachomatis

Emma Kathrine Lorenzen; Frank Follmann; Sarah Henriette Bøje; Karin Susanne Erneholm; Anja Weinreich Olsen; Jørgen Steen Agerholm; Gregers Jungersen; Peter  Andersen

doi:10.3389/fimmu.2015.00628

Intramuscular priming and intranasal boosting induce strong genital immunity through secretory IgA in minipigs infected with Chlamydia trachomatis

Emma Kathrine Lorenzen, Frank Follmann, Sarah Henriette Bøje, Karin Susanne Erneholm, Anja Weinreich Olsen, Jørgen Steen Agerholm, Gregers Jungersen, Peter Andersen

36 Citations (Scopus)

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Abstract

International efforts in developing a vaccine against Chlamydia trachomatis have highlighted the need for novel immunization strategies for the induction of genital immunity. In this study, we evaluated an intramuscular (IM) prime/intranasal boost vaccination strategy in a Göttingen Minipig model with a reproductive system very similar to humans. The vaccine was composed of C. trachomatis subunit antigens formulated in the Th1/Th17 promoting CAF01 adjuvant. IM priming immunizations with CAF01 induced a significant cell-mediated interferon gamma and interleukin 17A response and a significant systemic high-titered neutralizing IgG response. Following genital challenge, intranasally boosted groups mounted an accelerated, highly significant genital IgA response that correlated with enhanced bacterial clearance on day 3 post infection. By detecting antigen-specific secretory component (SC), we showed that the genital IgA was locally produced in the genital mucosa. The highly significant inverse correlation between the vaginal IgA SC response and the chlamydial load suggests that IgA in the minipig model is involved in protection against C. trachomatis. This is important both for our understanding of protective immunity and future vaccination strategies against C. trachomatis and genital pathogens in general.

Original language	English
Article number	628
Journal	Frontiers in Immunology
Volume	6
Number of pages	12
ISSN	1664-3224
DOIs	https://doi.org/10.3389/fimmu.2015.00628
Publication status	Published - 16 Dec 2015

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title = "Intramuscular priming and intranasal boosting induce strong genital immunity through secretory IgA in minipigs infected with Chlamydia trachomatis",

abstract = "International efforts in developing a vaccine against Chlamydia trachomatis have highlighted the need for novel immunization strategies for the induction of genital immunity. In this study, we evaluated an intramuscular (IM) prime/intranasal boost vaccination strategy in a G{\"o}ttingen Minipig model with a reproductive system very similar to humans. The vaccine was composed of C. trachomatis subunit antigens formulated in the Th1/Th17 promoting CAF01 adjuvant. IM priming immunizations with CAF01 induced a significant cell-mediated interferon gamma and interleukin 17A response and a significant systemic high-titered neutralizing IgG response. Following genital challenge, intranasally boosted groups mounted an accelerated, highly significant genital IgA response that correlated with enhanced bacterial clearance on day 3 post infection. By detecting antigen-specific secretory component (SC), we showed that the genital IgA was locally produced in the genital mucosa. The highly significant inverse correlation between the vaginal IgA SC response and the chlamydial load suggests that IgA in the minipig model is involved in protection against C. trachomatis. This is important both for our understanding of protective immunity and future vaccination strategies against C. trachomatis and genital pathogens in general.",

author = "Lorenzen, {Emma Kathrine} and Frank Follmann and B{\o}je, {Sarah Henriette} and Erneholm, {Karin Susanne} and Olsen, {Anja Weinreich} and Agerholm, {J{\o}rgen Steen} and Gregers Jungersen and Peter Andersen",

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doi = "10.3389/fimmu.2015.00628",

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T1 - Intramuscular priming and intranasal boosting induce strong genital immunity through secretory IgA in minipigs infected with Chlamydia trachomatis

AU - Lorenzen, Emma Kathrine

AU - Follmann, Frank

AU - Bøje, Sarah Henriette

AU - Erneholm, Karin Susanne

AU - Olsen, Anja Weinreich

AU - Agerholm, Jørgen Steen

AU - Jungersen, Gregers

AU - Andersen, Peter

PY - 2015/12/16

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N2 - International efforts in developing a vaccine against Chlamydia trachomatis have highlighted the need for novel immunization strategies for the induction of genital immunity. In this study, we evaluated an intramuscular (IM) prime/intranasal boost vaccination strategy in a Göttingen Minipig model with a reproductive system very similar to humans. The vaccine was composed of C. trachomatis subunit antigens formulated in the Th1/Th17 promoting CAF01 adjuvant. IM priming immunizations with CAF01 induced a significant cell-mediated interferon gamma and interleukin 17A response and a significant systemic high-titered neutralizing IgG response. Following genital challenge, intranasally boosted groups mounted an accelerated, highly significant genital IgA response that correlated with enhanced bacterial clearance on day 3 post infection. By detecting antigen-specific secretory component (SC), we showed that the genital IgA was locally produced in the genital mucosa. The highly significant inverse correlation between the vaginal IgA SC response and the chlamydial load suggests that IgA in the minipig model is involved in protection against C. trachomatis. This is important both for our understanding of protective immunity and future vaccination strategies against C. trachomatis and genital pathogens in general.

AB - International efforts in developing a vaccine against Chlamydia trachomatis have highlighted the need for novel immunization strategies for the induction of genital immunity. In this study, we evaluated an intramuscular (IM) prime/intranasal boost vaccination strategy in a Göttingen Minipig model with a reproductive system very similar to humans. The vaccine was composed of C. trachomatis subunit antigens formulated in the Th1/Th17 promoting CAF01 adjuvant. IM priming immunizations with CAF01 induced a significant cell-mediated interferon gamma and interleukin 17A response and a significant systemic high-titered neutralizing IgG response. Following genital challenge, intranasally boosted groups mounted an accelerated, highly significant genital IgA response that correlated with enhanced bacterial clearance on day 3 post infection. By detecting antigen-specific secretory component (SC), we showed that the genital IgA was locally produced in the genital mucosa. The highly significant inverse correlation between the vaginal IgA SC response and the chlamydial load suggests that IgA in the minipig model is involved in protection against C. trachomatis. This is important both for our understanding of protective immunity and future vaccination strategies against C. trachomatis and genital pathogens in general.

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Intramuscular priming and intranasal boosting induce strong genital immunity through secretory IgA in minipigs infected with Chlamydia trachomatis

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