Adjuvant effects of CpG oligodeoxynucleotides on responses against T‐independent type 2 antigens

Kovařík, Jiří; Bozzotti, Paola; Tougne, Chantal; Davis, H. L.; Lambert, Paul Henri; Krieg, AM; Siegrist, Claire‐Anne

doi:10.1046/j.1365-2567.2001.01158.x

Cited by 39 publications

(27 citation statements)

References 38 publications

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“…Note that in their report, the researcher only tested coadministration of the CpG ODNs with the PS vaccine. 21 By contrast coadministration of Pneumovax with the TLR4 agonist, monophosphoryl lipid A, has been shown to enhance the antibody response in adult and aged mice. 30 From a mechanistic point of view, the reason why TLR agonists require to be administrated at least 1 day after immunization to exert their adjuvant effects remains an open question.…”

Section: Discussionmentioning

confidence: 99%

“…In a coadministration protocol, CpG ODNs have been reported to amplify the Ab response to PS-protein conjugates 19,20 or to NP-Ficoll but not to a plain PS vaccine. 21 To reconsider the effect of TLR agonists on TI B-cell responses, we conducted experiments in which CpG1668 was administrated subcutaneously before immunization, at the time of immunization, or after immunization with PS3. The anti-PS3 IgM response was not affected when CpG1668 was injected 1 day before PS3 immunization but was consistently inhibited when PS3 and CpG1668 were coinjected ( Figure 1A).…”

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confidence: 99%

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The thymus-independent immunity conferred by a pneumococcal polysaccharide is mediated by long-lived plasma cells

Taillardet

Haffar

Mondière

et al. 2009

Blood

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It was recently shown that bacterial thymus-independent (TI) antigens confer long-lasting immunity and generate memory B lymphocytes. However, reactivation of TI memory B cells is repressed in immunocompetent mice, thus raising the issue of the mechanism whereby TI vaccines confer immune protection. Here, we propose an explanation to this apparent paradox by showing that a Streptococcus pneumoniae capsular polysaccharide (PS) generates long-lived bone marrow (BM) plasma cells which frequency can be increased by CpG oligodeoxynucleotides (ODNs). The adjuvant effect of CpG ODNs on the PS3 Ab response is directly targeted to B cells and does not involve B-1a cells. We also demonstrated that BM plasma cells generated in response to the thymus-dependent (TD) form of the PS vaccine have a higher secretion capacity than those produced after immunization with the CpGadjuvanted PS vaccine. Finally, we show that the PS-specific BM plasma cell compartment is sufficient to confer full protection of vaccinated mice against S pneumoniae infection. Altogether, our results show that TI antigens like their TD counterparts can generate both the lymphoid and the plasma cell component of B-cell memory. They also provide a framework for the improvement and widespread usage of TI vaccines. IntroductionDespite advances in antimicrobial therapy, infections with extracellular polysaccharide (PS)-encapsulated bacteria remain an important clinical problem and a primary source of death worldwide. Pathogenic bacteria including Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae express capsular PSs that behave as prototypic thymus-independent (TI) antigens (Ags). These Ags have initially been defined on the basis of their ability to elicit an antibody (Ab) response in T cell-deficient or athymic mice by a mechanism that requires expression of a functional Bruton tyrosine kinase. 1 They are mostly nonpeptidic molecules, which in their great majority, are unable to follow the conventional Agprocessing pathway leading to presentation by MHC class I and II molecules. 2 To overcome systemic infections by encapsulated extracellular bacteria such as S pneumoniae, B cells rapidly generate a protective Ab response against capsular PS. B-1 and marginal zone B cells have been envisioned as key players in the humoral response against TI Ags. 3 More recently, 2 studies, using Borrelia hermsii or capsular PSs from S pneumoniae as immunogens, have shown that B-1b cells are critically involved in bacterial clearance in vaccinated mice. 4,5 It has long been thought that the generation of memory B cells is restricted to thymus-dependent (TD) responses. However, the recent observation that adoptive transfer of B-1b cells from donor mice immunized with whole bacteria can confer long-lasting TI immunity to immunodeficient mice shows that TI Ags generate B-cell memory and that this function can be assigned to the B-1b-cell subset. 5 Nonetheless, the concept of TI B-cell memory is at odds with the fact that, unlike TD Ags, TI Ags fail to...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

The thymus-independent immunity conferred by a pneumococcal polysaccharide is mediated by long-lived plasma cells

Taillardet

Haffar

Mondière

et al. 2009

Blood

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“…It has been shown that adjuvants not only can improve the immunogenicity of conjugate vaccines but also can direct the antipolysaccharide antibody isotype switch toward the desired IgG subclasses (80,81). CpG ODN 1826 (82) was shown to enhance the isotype switching from IgM to IgG2a and IgG3 subclasses for pneumococcal conjugates in a serotype-and mouse age-dependent manner (43,80,83). In our study, CpG ODN 1826 failed to significantly improve the immunogenicity of the S. suis type 2 CPS mixed conjugate or to induce isotype switching.…”

Section: Figmentioning

confidence: 99%

“…Conditions differing from those used in this study, such as the vaccine and adjuvant doses, might explain the observed differences. The biochemical properties of different CPSs might also influence the adjuvant capacity of CpG (83). As such, the choice of adjuvant is vital to maximize isotype switching.…”

Section: Figmentioning

confidence: 99%

Protection against Streptococcus suis Serotype 2 Infection Using a Capsular Polysaccharide Glycoconjugate Vaccine

et al. 2016

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dStreptococcus suis serotype 2 is an encapsulated bacterium and one of the most important bacterial pathogens in the porcine industry. Despite decades of research for an efficient vaccine, none is currently available. Based on the success achieved with other encapsulated pathogens, a glycoconjugate vaccine strategy was selected to elicit opsonizing anti-capsular polysaccharide (anti-CPS) IgG antibodies. In this work, glycoconjugate prototypes were prepared by coupling S. suis type 2 CPS to tetanus toxoid, and the immunological features of the postconjugation preparations were evaluated in vivo. In mice, experiments evaluating three different adjuvants showed that CpG oligodeoxyribonucleotide (ODN) induces very low levels of anti-CPS IgM antibodies, while the emulsifying adjuvants Stimune and TiterMax Gold both induced high levels of IgGs and IgM. Dose-response trials comparing free CPS with the conjugate vaccine showed that free CPS is nonimmunogenic independently of the dose used, while 25 g of the conjugate preparation was optimal in inducing high levels of anti-CPS IgGs postboost. With an opsonophagocytosis assay using murine whole blood, sera from immunized mice showed functional activity. Finally, the conjugate vaccine showed immunogenicity and induced protection in a swine challenge model. When conjugated and administered with emulsifying adjuvants, S. suis type 2 CPS is able to induce potent IgM and isotype-switched IgGs in mice and pigs, yielding functional activity in vitro and protection against a lethal challenge in vivo, all features of a T cell-dependent response. This study represents a proof of concept for the potential of glycoconjugate vaccines in veterinary medicine applications against invasive bacterial infections.

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“…An effective way of generating cellmediated immunity is by DNA-based immunization. Numerous approaches are available for enhancing DNA-based immune responses, including the coadministration of cytokine expressing plasmids (9,14), the use of immunostimulatory DNA sequences (15), the use of Salmonella vectors (32), and targeting of DNA to dendritic cells (33). In our previous studies with DNA-based immunization against HBV (18) and HCV (20), we found that the use of a recombinant poxvirus as a booster months after immunization with DNA produced a much stronger booster effect than that obtained when DNA was used as a booster.…”

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confidence: 99%

DNA Immunization with Hepatitis C Virus (HCV) Polycistronic Genes or Immunization by HCV DNA Priming-Recombinant Canarypox Virus Boosting Induces Immune Responses and Protection from Recombinant HCV-Vaccinia Virus Infection in HLA-A2.1-Transgenic Mice

Pancholi

Perkus

Tricoche

et al. 2003

J Virol

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We studied immune responses to hepatitis C virus (HCV) genes delivered as DNA encoding the entire HCV protein coding genome in two polycistronic plasmids encoding HCV capsid-E1-E2-NS2-NS3 and HCV NS3-NS4-NS5 in HLA-A2.1-transgenic mice. Immune responses to HCV DNA prime and recombinant canarypox virus boost were also studied with the above constructs. At 8 weeks after a canarypox virus boost, the DNA prime/canarypox virus boosting regimen induced potent cellular immune responses to HCV structural and nonstructural proteins on target cells expressing the HLA-A2.1 allele. High frequencies of gamma interferonsecreting cells, as detected by enzyme-linked immunospot assay, were obtained in response to several endogenously expressed HCV proteins. We also observed cytotoxic-T-lymphocyte reactivity in response to endogenously expressed HCV proteins in fresh spleen cells without in vitro expansion. Upon challenge with a recombinant vaccinia virus expressing HCV proteins at 2 months postimmunization, the HCV DNA prime/ canarypox virus-immunized mice showed a complete reduction in vaccinia virus titers compared to HCV DNA prime/boost-and mock-immunized controls. Immune responses were still detectable 4 months after canarypox virus boost in immunized mice. Interestingly, at 10 months postimmunization (8 months after canarypox virus boost), the protection in HCV DNA prime/boost-immunized mice against recombinant HCV-vaccinia virus challenge was higher than that observed in HCV DNA prime/canarypox virus boost-immunized mice.About 80% of human hepatitis C virus (HCV) infections become chronic with lifelong viremia. It is estimated that there are more than 200 million chronically HCV-infected carriers in the world, 4 million of whom are in the United States (3). Treatment of the carrier state is at present not very satisfactory. HCV is a notoriously difficult target for immunization: it exists in numerous genotypes and within an infected host in numerous quasispecies (5). It is therefore desirable to develop a strategy that will induce strong immune responses to several variable and conserved regions of the virus.Immunization against HCV will involve the generation of cell-mediated immunity to mediate killing or downregulation of infected cells (7,11). An effective way of generating cellmediated immunity is by DNA-based immunization. Numerous approaches are available for enhancing DNA-based immune responses, including the coadministration of cytokine expressing plasmids (9, 14), the use of immunostimulatory DNA sequences (15), the use of Salmonella vectors (32), and targeting of DNA to dendritic cells (33). In our previous studies with DNA-based immunization against HBV (18) and HCV (20), we found that the use of a recombinant poxvirus as a booster months after immunization with DNA produced a much stronger booster effect than that obtained when DNA was used as a booster.In the present study we evaluated plasmid DNA immunization with polycistronic gene constructs encoding the whole protein coding HCV genome in HLA-A2.1-transgen...

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Adjuvant effects of CpG oligodeoxynucleotides on responses against T‐independent type 2 antigens

Cited by 39 publications

References 38 publications

The thymus-independent immunity conferred by a pneumococcal polysaccharide is mediated by long-lived plasma cells

The thymus-independent immunity conferred by a pneumococcal polysaccharide is mediated by long-lived plasma cells

Protection against Streptococcus suis Serotype 2 Infection Using a Capsular Polysaccharide Glycoconjugate Vaccine

DNA Immunization with Hepatitis C Virus (HCV) Polycistronic Genes or Immunization by HCV DNA Priming-Recombinant Canarypox Virus Boosting Induces Immune Responses and Protection from Recombinant HCV-Vaccinia Virus Infection in HLA-A2.1-Transgenic Mice

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