CpG Oligodeoxynucleotides Adsorbed onto Polylactide-Co-Glycolide Microparticles Improve the Immunogenicity and Protective Activity of the Licensed Anthrax Vaccine

Xie, Hang; Gürsel, İhsan; Ivins, Bruce E.; Singh, Manmohan; O’Hagan, Derek T.; Ulmer, Jeffrey B.; Klinman, Dennis M.

doi:10.1128/iai.73.2.828-833.2005

Cited by 108 publications

(109 citation statements)

References 39 publications

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“…Concentration of molecular adjuvants in lymph nodes (LNs) using nanoparticle carriers can enable profound dose sparing of molecular adjuvants, and this approach has been demonstrated for a number of TLR agonists, including MPLA, CpG DNA, poly(I:C), and small-molecule TLR7/8 compounds (27)(28)(29)(30)(31)(32)(33). Importantly, a number of TLR agonist-carrying particle formulations have been demonstrated to effectively adjuvant the immune response when simply admixed with particulate or soluble antigen, i.e., without requiring coincorporation of antigen and adjuvant together in particles (32,(34)(35)(36). Liposomal and oil-based nanoparticle emulsions carrying TLR agonists have also been shown to be effective in early-stage clinical trials (5,37,38).…”

Section: Cd8αmentioning

confidence: 99%

Nanoparticulate STING agonists are potent lymph node–targeted vaccine adjuvants

Hanson¹,

Crespo²,

Abraham³

et al. 2015

J. Clin. Invest.

323

310

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Section: Cd8αmentioning

confidence: 99%

Nanoparticulate STING agonists are potent lymph node–targeted vaccine adjuvants

Hanson¹,

Crespo²,

Abraham³

et al. 2015

J. Clin. Invest.

323

310

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“…These toxins are classic A-B toxins, where lethal factor and edema factor represent the active moieties and protective antigen (PA) represents the cell-binding moiety (5,6,20). Humoral immunity to PA can successfully mediate protection from lethal challenges in animal models of inhalation anthrax, and the protection is correlated with the ability of PA-specific antibodies to neutralize LeTx in vitro in the toxin neutralization assay (TNA) (17,21,22,35,36,41).While PA-specific antibody titer has been shown to correlate with TNA titers in vitro, this relationship demonstrates variability among different studies and in different species (19,37,40,43,48,50). Most PA-specific neutralizing monoclonal antibodies (MAbs) show a more invariable linear relationship between concentration and toxin neutralization (4, 46).…”

mentioning

confidence: 99%

A Heterologous Helper T-Cell Epitope Enhances the Immunogenicity of a Multiple-Antigenic-Peptide Vaccine Targeting the Cryptic Loop-Neutralizing Determinant ofBacillus anthracisProtective Antigen

Oscherwitz

Cease

2009

Infect Immun

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We previously showed that a multiple antigenic peptide (MAP) displaying amino acids (aa) 305 to 319 from the 2␤2-2␤3 loop of protective antigen (PA) can elicit high-titered antibody that neutralizes lethal toxin (LeTx) in vitro and that this loop-neutralizing determinant (LND) specificity is absent in PA-immune rabbits. Some immune rabbits were, however, nonresponders to the MAP. We hypothesized that the immunogen elicited suboptimal major histocompatibility complex (MHC) class II-restricted T-cell help and that introduction of a functional helper T-cell epitope would increase MHC-restricted responsiveness and the magnitude and affinity of the antibody responses. In the current study, we characterized the T-and B-cell responses to LND peptides in mice, then designed second-generation MAP immunogens for eliciting LND-specific immunity, and tested them in rabbits. Bacillus anthracis is a gram-positive, spore-forming bacterium that naturally infects wildlife and livestock and, less frequently, humans. Since 2001, when spores of B. anthracis sent through the U.S mail resulted in infection in 22 individuals, including five fatal cases of inhalation anthrax, considerable effort has been directed toward reevaluating our preparedness for possible bioterrorist threats, including weaponized anthrax.The morbidity and mortality associated with inhalation anthrax are largely a result of the elaboration of two toxins, lethal toxin (LeTx) and edema toxin. These toxins are classic A-B toxins, where lethal factor and edema factor represent the active moieties and protective antigen (PA) represents the cell-binding moiety (5,6,20). Humoral immunity to PA can successfully mediate protection from lethal challenges in animal models of inhalation anthrax, and the protection is correlated with the ability of PA-specific antibodies to neutralize LeTx in vitro in the toxin neutralization assay (TNA) (17,21,22,35,36,41).While PA-specific antibody titer has been shown to correlate with TNA titers in vitro, this relationship demonstrates variability among different studies and in different species (19,37,40,43,48,50). Most PA-specific neutralizing monoclonal antibodies (MAbs) show a more invariable linear relationship between concentration and toxin neutralization (4, 46). These findings can be reconciled, in part, by the fact that only a fraction of the polyclonal antibody produced in response to vaccination with PA contributes to LeTx neutralization (4,39,40). Indeed, analyses of human and murine MAbs suggest that whereas immunization with whole PA elicits antibodies to a wide range of sequences within the protein, the repertoire of neutralizing antibodies is considerably more focused, limited perhaps to only a couple of major regions in PA, including the anthrax toxin receptor binding region in domain 4 and the lethal factor-and edema factor-binding regions in domain 1 (4,24,25,40). Though PA-specific antibody may contribute to protection through mechanisms other than neutralization, for example, by facilitating opsonization of spores (...

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“…Treatment with ODN or PIC results in strong cytokine/chemokine induction, establishing an antiviral state within the host. Accordingly, ODN and PIC have been used as components of vaccine formulations to enhance the host's immune response (15)(16)(17)(18)(19)(20), and further studies have shown that adjuvants containing both ODN and PIC can enhance the immunogenicity of vaccines (21,22). Although ODN and PIC can each induce an antiviral immune response within the host, the responses differ in expression profile, cellular localization, and signaling pathways (23).…”

mentioning

confidence: 99%

Liposome-Antigen-Nucleic Acid Complexes Protect Mice from Lethal Challenge with Western and Eastern Equine Encephalitis Viruses

Phillips

Schountz

Toth

et al. 2014

J Virol

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Alphaviruses are mosquito-borne viruses that cause significant disease in animals and humans. Western equine encephalitis virus (WEEV) and eastern equine encephalitis virus (EEEV), two New World alphaviruses, can cause fatal encephalitis, and EEEV is a select agent of concern in biodefense. However, we have no antiviral therapies against alphaviral disease, and current vaccine strategies target only a single alphavirus species. In an effort to develop new tools for a broader response to outbreaks, we designed and tested a novel alphavirus vaccine comprised of cationic lipid nucleic acid complexes (CLNCs) and the ectodomain of WEEV E1 protein (E1ecto). Interestingly, we found that the CLNC component, alone, had therapeutic efficacy, as it increased survival of CD-1 mice following lethal WEEV infection. Immunization with the CLNC-WEEV E1ecto mixture (lipid-antigennucleic acid complexes [LANACs]) using a prime-boost regimen provided 100% protection in mice challenged with WEEV subcutaneously, intranasally, or via mosquito. Mice immunized with LANACs mounted a strong humoral immune response but did not produce neutralizing antibodies. Passive transfer of serum from LANAC E1ecto-immunized mice to nonimmune CD-1 mice conferred protection against WEEV challenge, indicating that antibody is sufficient for protection. In addition, the LANAC E1ecto immunization protocol significantly increased survival of mice following intranasal or subcutaneous challenge with EEEV. In summary, our LANAC formulation has therapeutic potential and is an effective vaccine strategy that offers protection against two distinct species of alphavirus irrespective of the route of infection. We discuss plausible mechanisms as well the potential utility of our LANAC formulation as a pan-alphavirus vaccine.

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CpG Oligodeoxynucleotides Adsorbed onto Polylactide-Co-Glycolide Microparticles Improve the Immunogenicity and Protective Activity of the Licensed Anthrax Vaccine

Cited by 108 publications

References 39 publications

Nanoparticulate STING agonists are potent lymph node–targeted vaccine adjuvants

Nanoparticulate STING agonists are potent lymph node–targeted vaccine adjuvants

A Heterologous Helper T-Cell Epitope Enhances the Immunogenicity of a Multiple-Antigenic-Peptide Vaccine Targeting the Cryptic Loop-Neutralizing Determinant ofBacillus anthracisProtective Antigen

Liposome-Antigen-Nucleic Acid Complexes Protect Mice from Lethal Challenge with Western and Eastern Equine Encephalitis Viruses

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