Vaginal immunization of Cynomolgus monkeys with Streptococcus gordonii expressing HIV-1 and HPV 16 antigens

Fabio, Simonetta Di; Medaglini, Donata; Rush, Catherine M.; Corrias, Franco; Panzini, Gianluca; Pace, Monica; Verani, P; Pozzi, Gianni; Titti, Fausto

doi:10.1016/s0264-410x(97)80002-3

Cited by 69 publications

(26 citation statements)

References 37 publications

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“…To check for the presence of recombinant S. gordonii in feces, dilutions of fecal samples were plated on blood agar plates containing streptomycin (500 g/ml). Bacterial colonies were counted, tested for resistance to erythromycin (1 g/ml) and for expression of LTB in immunoblot, as previously described (12,26,27,39).…”

Section: Methodsmentioning

confidence: 99%

“…The concentrations of LTBspecific antibodies were normalized to those of total antibodies, and results were expressed in micrograms of LTB-specific IgG, IgG1, or IgG2a per milligram of total IgG, IgG1, or IgG2a, respectively. To reduce sample variability, the amounts of LTB-specific IgA or IgG were normalized to the concentrations of total IgA or IgG calculated for each sample (12,26,27). The total IgA or IgG content was determined using microtiter plates (medium binding capacity; Greiner) coated with 100 l of goat anti-mouse IgA or IgG (1 g/ml; Southern Biotechnology Associates).…”

Section: Methodsmentioning

confidence: 99%

“…The genetic system for heterologous gene expression in S. gordonii allows surface expression of recombinant proteins, since it is based on the use of the streptococcal surface protein M6 as a fusion partner (35,37,39,41). Recombinant strains of S. gordonii expressing heterologous antigens were shown to induce systemic and local immune responses by colonizing the host mucosal surfaces (12,26,27,33,41). Here, we show that the LTB monomer expressed on the surface of S. gordonii can induce LTB-specific local and systemic antibodies after immunization with recombinant bacteria.…”

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confidence: 99%

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Immunogenicity of the B Monomer ofEscherichia coliHeat-Labile Toxin Expressed on the Surface ofStreptococcus gordonii

et al. 2000

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The B monomer of the Escherichia coli heat-labile toxin (LTB) was expressed on the surface of the human oral commensal bacterium Streptococcus gordonii. Recombinant bacteria expressing LTB were used to immunize BALB/c mice subcutaneously and intragastrically. The LTB monomer expressed on the streptococcal surface proved to be highly immunogenic, as LTB-specific immunoglobulin G (IgG) serum titers of 140,000 were induced after systemic immunization. Most significantly, these antibodies were capable of neutralizing the enterotoxin in a cell neutralization assay. Following mucosal delivery, antigen-specific IgA antibodies were found in feces and antigen-specific IgG antibodies were found in sera. Analysis of serum IgG subclasses showed a clear predominance of IgG1 when recombinant bacteria were inoculated subcutaneously, while a prevalence of IgG2a was observed upon intragastric delivery, suggesting, in this case, the recruitment of a Th1 type of immune response.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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confidence: 99%

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Immunogenicity of the B Monomer ofEscherichia coliHeat-Labile Toxin Expressed on the Surface ofStreptococcus gordonii

et al. 2000

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“…S. gordonii, a gram-positive coccus and a normal commensal of the human oral cavity, has been used as the carrier for mucosal delivery of heterologous vaccine antigens in both mice and nonhuman primates (7,15,16). In this study, we used a recombinant strain of S. gordonii (GP1253) expressing TTFC fused with the M6 protein on the cell surface and the parental strain GP1221 as the control (3,21).…”

Section: Resultsmentioning

confidence: 99%

“…These approaches have been used for inducing protective immune responses against viral and tumor antigens in mouse models (6,17,26). In particular, recombinant strains of Streptococcus gordonii, which is a commensal bacterium of the human oral cavity, induce both local and systemic antibody responses, as well as a T-cell response, to viral antigens in both mice and macaques (7,15,16). However, the APCs and the mechanisms involved in these bacterium-based immunostimulating systems have been only marginally investigated.…”

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Human Dendritic Cells Are Superior to B Cells at Presenting a Major Histocompatibility Complex Class II-Restricted Heterologous Antigen Expressed on RecombinantStreptococcus gordonii

et al. 2000

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Bacteria are being actively investigated as vaccine carriers for inducing or boosting protective immune responses. In this study, human monocyte-derived dendritic cells (DCs) and normal B cells were compared for their capacity to present the C fragment of tetanus toxin (TTFC), expressed on the surface of recombinant Streptococcus gordonii, to specific CD4 ؉ T lymphocytes. DCs were more efficient than B cells at presenting soluble TTFC and remarkably more capable of presenting bacterium-associated TTFC both in terms of the amount of antigen required to obtain a given T-cell response and on a per-cell basis. This difference was associated with a much lower capacity of B cells to endocytose soluble TTFC and phagocytose recombinant S. Recent efforts in developing more efficacious vaccine strategies have pointed to the use of bacteria as vectors of heterologous antigens. Bacteria can be easily manipulated at the genetic level and can be engineered to express the gene product in different forms (11,21,26). Alternatively, attenuated bacteria can serve as carriers for delivering antigen-encoding DNA to antigen-presenting cells (APCs) (6,17,30). These approaches have been used for inducing protective immune responses against viral and tumor antigens in mouse models (6,17,26). In particular, recombinant strains of Streptococcus gordonii, which is a commensal bacterium of the human oral cavity, induce both local and systemic antibody responses, as well as a T-cell response, to viral antigens in both mice and macaques (7,15,16). However, the APCs and the mechanisms involved in these bacterium-based immunostimulating systems have been only marginally investigated.Dendritic cells (DCs) and B lymphocytes show important differences in their APC functions (1, 19). They differ in the capacity to endocytose antigens, to cluster with T cells, to provide proper costimulation, and to secrete regulatory cytokines (2,5,9,13,28). A number of studies have indeed demonstrated that DCs are much more potent APCs than are antigen-specific and non-antigen-specific B lymphocytes in the activation of both naive and memory T cells (2,4,9,14,20,27). Most experiments, however, has been performed using soluble antigens given in the form of native proteins or immunogenic peptides, and very few studies have compared the capacity of DCs and B cells to present particulate or bacterium-associated antigens (8,23,29).Mouse DCs present a major histocompatibility complex (MHC) class I-restricted heterologous antigen, expressed on the surface of recombinant S. gordonii, to T lymphocytes at high efficiency, and S. gordonii induces neobiosynthesis and membrane stabilization of MHC class I and class II molecules (25). Moreover, human DCs fed with recombinant bacteria stimulated the specific CD4 ϩ -T-cell response with much higher efficiency than did DCs pulsed with soluble antigen. Finally, S. gordonii provided a potent stimulus for inducing DC maturation and release of chemokines active on T cells (3). In the present study, DCs and B cells were compared for th...

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Cervical cancer vaccines: Emerging concepts and developments

et al. 2001

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Certain human cancers are linked to infection by oncogenic viruses that are able to cause transformation of the normal host cell into a cancerous cell. Human papillomavirus (HPV) DNA and expression of viral transforming proteins are found in virtually all cervical cancer cells, indicating an important role of this virus in the pathogenesis of the disease. Evidence exists that the immune response to cancer cells can play a major role in determining the outcome of disease. The fact that HPV is a necessary cause for cervical cancer provides a clear opportunity to develop a therapeutic vaccine against the virus to treat patients with cervical cancer at its early and late stages. Development of a prophylactic vaccine for HPV would also reduce the incidence of cervical neoplasias by preventing virus infection. Various candidate HPV vaccines are being developed and tested in animal models and/or in human clinical trials. These HPV vaccines, both preventive and therapeutic, are the subjects of this review.

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Vaginal immunization of Cynomolgus monkeys with Streptococcus gordonii expressing HIV-1 and HPV 16 antigens

Cited by 69 publications

References 37 publications

Immunogenicity of the B Monomer ofEscherichia coliHeat-Labile Toxin Expressed on the Surface ofStreptococcus gordonii

Immunogenicity of the B Monomer ofEscherichia coliHeat-Labile Toxin Expressed on the Surface ofStreptococcus gordonii

Human Dendritic Cells Are Superior to B Cells at Presenting a Major Histocompatibility Complex Class II-Restricted Heterologous Antigen Expressed on RecombinantStreptococcus gordonii

Cervical cancer vaccines: Emerging concepts and developments

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