Safety and immunogenicity of the chlamydia vaccine candidate CTH522 adjuvanted with CAF01 liposomes or aluminium hydroxide: a first-in-human, randomised, double-blind, placebo-controlled, phase 1 trial

Abraham, Sonya; Juel, Helene Bæk; Bang, Peter Fibiger; Cheeseman, Hannah; Dohn, Rebecca B; Cole, Tom; Kristiansen, Max; Korsholm, Karen Smith; Lewis, David; Olsen, Anja; McFarlane, Leon R.; Day, Suzanne; Knudsen, Sara; Moen, Kjersti; Rühwald, Morten; Kromann, Ingrid; Andersen, Peter; Shattock, Robin J.; Follmann, Frank

doi:10.1016/s1473-3099(19)30279-8

Cited by 132 publications

(128 citation statements)

References 29 publications

(40 reference statements)

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“…It is important to note that there may be species-specific differences in recognition and activation of this MIN-CLE receptor. It is well known that CAF01 is a promising adjuvant in humans, inducing both antibody and CMI responses [16,34] and also that CAF01 combined with Chlamydia trachomatis fusion proteins (Hirep1 and CTH93) induce strong CMI responses in Göttingen minipigs [46]. Nevertheless, whether TDB is also an effective immunostimulator in poultry remains to be assessed and further studies are therefore required to develop the CAF01 + NG-34 as a vaccine for poultry.…”

Section: Discussionmentioning

confidence: 99%

“…The four adjuvants tested (Alhydrogel 2.0%, AddaVax ™ , cationic adjuvant formulation 01 (CAF01) and Diluvac Forte ® ) were selected in view of their dissimilar immunological profiles and mechanisms of adjuvanticity (O'Hagan and Valiante [2]) summarized in Table 1. Among them, Alhydrogel 2.0% and AddaVax ™ (similar to MF59 ® ) are formulated in human registered vaccines while CAF01 is in clinical development stages [16]. Diluvac Forte ® , however, is applied only in veterinary studies and has been widely utilized in swine protein vaccines [17,18].…”

Section: Introductionmentioning

confidence: 99%

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Influenza NG-34 T cell conserved epitope adjuvanted with CAF01 as a possible influenza vaccine candidate

Sisteré-Oró

Pedersen

Córdoba

et al. 2020

Vet Res

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Conserved epitopes are targets commonly researched to be part of universal vaccine candidates against influenza viruses (IV). These conserved epitopes need to be cross-protecting against distinct IV subtypes and to have a strong immunogenic potential. Nevertheless, subunit vaccines generally require a strong adjuvant to enhance their immunological effects. Herewith, we compare four different adjuvants differing in their immunological signatures that may enhance efficacy of a conserved hemagglutinin (HA)-epitope from IV, the NG-34, to define the most efficient combination of antigen/adjuvant to combat IV infections. Soluble NG-34 was mixed with adjuvants like aluminium hydroxide (AH) and AddaVax, known to induce Th2 and humoral responses; CAF01 which displays a biased Th1/Th17 profile and Diluvac Forte which augments the humoral response. Combinations were tested in different groups of mice which were subjected to immunological analyses. CAF01 + NG-34 induced a complete immune response with the highest IgG1, IgG2c titers and percentages of activated CD4 T cell promoting IFN-γ, IL-2 and TNF-α producing cells. Furthermore, in NG-34 stimulated mice splenocytes, cytokine levels of IFN-γ, IL-1β, IL-6, IL-10, IL-17 and TNF-α were also the highest in the CAF01 + NG-34 mouse group. This complete induced immune response covering the humoral and the cellular arms of the adaptive immunity promoted by CAF01 + NG-34 group suggests that CAF01 could be a good candidate as an adjuvant to combine with NG-34 for an efficacious vaccine against IV. However, more studies performed in IV hosts as well as studies with a challenge model are further required.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Influenza NG-34 T cell conserved epitope adjuvanted with CAF01 as a possible influenza vaccine candidate

Sisteré-Oró

Pedersen

Córdoba

et al. 2020

Vet Res

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“…The vaccine consisted of the C.t. vaccine antigen CTH522, 31,32 formulated in the adjuvant CAF01 (cationic adjuvant formulation 01), which possess a unique property of inducing circulating Th1 T cells as well as Th17 T cells. 33 The data showed that a nonmucosal parenteral vaccine induced systemic immunity able to protect against a TC infection.…”

Section: Introductionmentioning

confidence: 99%

Parenteral vaccination protects against transcervical infection with Chlamydia trachomatis and generate tissue-resident T cells post-challenge

et al. 2020

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The optimal protective immunity against Chlamydia trachomatis (C.t.) is still not fully resolved. One of the unresolved issues concerns the importance of resident immunity, since a recent study showed that optimal protection against a transcervical (TC) infection required genital tissue-resident memory T cells. An important question in the Chlamydia field is therefore if a parenteral vaccine strategy, inducing only circulating immunity primed at a nonmucosal site, should be pursued by Chlamydia vaccine developers. To address this question we studied the protective efficacy of a parenteral Chlamydia vaccine, formulated in the Th1/ Th17 T cell-inducing adjuvant CAF01. We found that a parenteral vaccination induced significant protection against a TC infection and against development of chronic pathology. Protection correlated with rapid recruitment of Th1/Th17 T cells to the genital tract (GT), which efficiently prevented infection-driven generation of low quality Th1 or Th17 T cells, and instead maintained a pool of high quality multifunctional Th1/Th17 T cells in the GT throughout the infection. After clearance of the infection, a pool of these cells settled in the GT as tissue-resident Th1 and Th17 cells expressing CD69 but not CD103, CD49d, or CCR7, where they responded rapidly to a reinfection. These results show that a nonmucosal parenteral strategy inducing Th1 and Th17 T cells mediates protection against both infection with C.t. as well as development of chronic pathology, and lead to post-challenge protective tissue-resident memory immunity in the genital tract.npj Vaccines (2020) 5:7 ; https://doi.

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“…No effective human chlamydia vaccines are available (7). An early, phase 1 clinical trial assessed the safety and immunogenicity of a novel C. trachomatis vaccine in humans (8,9), but that vaccine would not be effective against C. abortus. An attenuated C. abortus vaccine is available for use in small ruminants but is not safe or approved for use in humans.…”

Section: Research Lettersmentioning

confidence: 99%

Chlamydia abortus in Pregnant Woman with Acute Respiratory Distress Syndrome

Pichon¹,

Guindre²,

Laroucau³

et al. 2020

Emerg. Infect. Dis.

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Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 26, No. 3, March 2020 629 RESEARCH LETTERS Figure. Radiographic and histologic images from a pregnant woman in rural France infected with Chlamydia abortus. A) Chest radiograph demonstrating bilateral pulmonary edema consistent with acute respiratory distress syndrome; B) hematoxylin and eosin (H&E) stained section of placenta showing acute histiocytic intervillitis zones (original magnification ×200); C) H&E stained section of placenta showing intervillitis hemorrhage (original magnification ×100); D) H&E stained section of placenta showing necrotizing mural arteritis (original magnification ×100).

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Safety and immunogenicity of the chlamydia vaccine candidate CTH522 adjuvanted with CAF01 liposomes or aluminium hydroxide: a first-in-human, randomised, double-blind, placebo-controlled, phase 1 trial

Cited by 132 publications

References 29 publications

Influenza NG-34 T cell conserved epitope adjuvanted with CAF01 as a possible influenza vaccine candidate

Influenza NG-34 T cell conserved epitope adjuvanted with CAF01 as a possible influenza vaccine candidate

Parenteral vaccination protects against transcervical infection with Chlamydia trachomatis and generate tissue-resident T cells post-challenge

Chlamydia abortus in Pregnant Woman with Acute Respiratory Distress Syndrome

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