Immunocorrelates of CAF family adjuvants

Pedersen, Gabriel Kristian; Andersen, Peter; Christensen, Dennis

doi:10.1016/j.smim.2018.10.003

Cited by 74 publications

(84 citation statements)

References 95 publications

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“…The results obtained in the AH + NG-34 partly correlated with the trend for a predominant Th2 differentiation and Th2-type cytokine profile, usually promoted by aluminum salts [31,32]. Statistically significant increase in CD4 CD44high population and highest IFN-γ, IL-2 and TNF-α responses (Th1-type cytokines) were observed in mice from CAF01 + NG34 (Figures 2A and C) as also reported in other studies [6,19,33,34]. Significantly higher titers of IFN-γ, TNF-α, IL-10, IL-17, IL-6 and IL-1β were also observed in the NG34stimulated spleen cell supernatants obtained from the CAF01 + NG-34 vaccinated animals ( Figures 3A, B, D, F-H).…”

Section: Discussionsupporting

confidence: 87%

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: Discussionsupporting

confidence: 87%

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 results showed that cells from vaccinated animals stimulated in vitro with CTH522 released both IFNγ and IL-17, in agreement with previous studies. 35 Six weeks following the last immunization, the animals were subjected to a TC infection and bacterial levels were determined in the uterus (upper genital tract, uGT) at day 7 post infection. The results showed that following infection with 10 5 IFUs the vaccine did not reduce the bacterial numbers significantly ( Fig.…”

Section: Resultsmentioning

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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“…The combination of DDA with the synthetic cord factor analogue trehalose 6,6-dibehenate (TDB) promotes protective immune responses without enhancing toxicity [2]. This adjuvant−termed CAF01−is stable, polarizes the T-cell response towards Th1/Th17 and activates macrophages by binding to MINCLE and triggering SYK/Card9/Bcl10/Malt-1 signaling [3].…”

Section: Introductionmentioning

confidence: 99%

“…H56:CAF01 elicits a Th1/Th17-CD4 T-cell response in the lung of Mycobacterium tuberculosis (Mtb) infected mice and provides prolonged control of infection in mice [4]. The CAF01 adjuvant system offers an ideal platform to include additional immune-stimulators to skew the immune response into the desired direction [2].…”

Section: Introductionmentioning

confidence: 99%

Toll like-receptor agonist Pam3Cys modulates the immunogenicity of liposomes containing the tuberculosis vaccine candidate H56

Kennerknecht

Noschka

Löffler

et al. 2020

Med Microbiol Immunol

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A major roadblock in the development of novel vaccines is the formulation and delivery of the antigen. Liposomes composed of a dimethyldioctadecylammonium (DDA) backbone and the adjuvant trehalose-6-6-dibehenate (TDB, termed "cationic adjuvant formulation (CAF01)", promote immunogenicity and protective efficacy of vaccines, most notably against infection with Mycobacterium tuberculosis. Specifically, the multicomponent antigen H56 delivered by CAF01 protects against tuberculosis in mice. Here we investigated whether the inclusion of immune-modulatory adjuvants into CAF01 modulates the immunogenicity of H56/CAF01 in vitro and in vivo. Based on our recent findings we selected the active sequence of the mycobacterial 19 kDa lipoprotein, Pam 3 Cys, which interacts with Toll like receptor 2 to induce an antimicrobial pathway. H56/CAF01-Pam 3 Cys liposomes were characterized for Pam 3 Cys incorporation, size, toxicity and activation of primary human macrophages. Macrophages efficiently take up H56/CAF01-Pam 3 Cys and trigger the release of significantly higher levels of TNF, IL-12 and IL-10 than H56/CAF01 alone. To evaluate the immunogenicity in vivo, we immunized mice with H56/CAF01-Pam 3 Cys and measured the release of IFN-γ and IL-17A by lymph node cells and spleen cells. While the antigen-specific production of IFN-γ was reduced by inclusion of Pam 3 Cys into H56/CAF01, the levels of IL-17A remained unchanged. In agreement with this finding, the concentration of the IFN-γ-associated IgG2a antibodies in the serum was lower than in H56/CAF01 immunized animals. These results provide proof of concept that Toll like-receptor agonist can be included into liposomes to modulate immune responses. The discordant results between the in vitro studies with human macrophages and in vivo studies in mice highlight the relevance and complexity of comparing immune responses in different species

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Immunocorrelates of CAF family adjuvants

Cited by 74 publications

References 95 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

Toll like-receptor agonist Pam3Cys modulates the immunogenicity of liposomes containing the tuberculosis vaccine candidate H56

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