Enhanced immunogenicity of pneumococcal surface adhesin A (PsaA) in mice via fusion to recombinant human B lymphocyte stimulator (BLyS)

Gor, Dennis O.; Ding, Xuedong; Li, Qing; Sultana, Dilara; Mambula, Salamatu S.; Bram, Richard J.; Greenspan, Neil S.

doi:10.1186/1745-6150-6-9

Cited by 14 publications

(11 citation statements)

References 55 publications

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“…We show that rRABV-mBAFF enhances the kinetics and magnitude of the anti-RABV G antibody response in mice. This is consistent with previous reports that BAFF is an effective adjuvant for viral and bacterial antigens, including HIV-1 envelope and pneumococcal surface adhesin A (29,30). Our findings dovetail with reports that dampening the BAFF signaling axis is an effective strategy to prevent autoimmune diseases such as arthritis, systemic lupus erythematosus, and type II diabetes by diminishing the antibody production and survival of autoreactive B cells (47)(48)(49).…”

Section: Discussionsupporting

confidence: 81%

“…Due to the specificity of receptor expression on B cells, BAFF has the ability to modulate a wide range of B cell functions, such as mediating B cell survival and proliferation (24)(25)(26)(27), inducing and maintaining T and B cell responses, including antibody-secreting PCs, the most important effector B cell population in the context of protection against RABV infection, and increasing protective IgG antibody titers (28). BAFF has been demonstrated to enhance antibody-mediated protection in models of other infectious diseases, including HIV, influenza, pneumococcus, malaria, Trypanosoma cruzi (Chagas' disease), and respiratory syncytial virus (23,(29)(30)(31)(32)(33). BAFF influences B cell proliferation, differentiation, and long-term survival of antiviral PCs during recovery from alphaviral encephalomyelitis (34).…”

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confidence: 99%

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Targeting Vaccine-Induced Extrafollicular Pathway of B Cell Differentiation Improves Rabies Postexposure Prophylaxis

Haley

Tzvetkov

Meuwissen

et al. 2017

J Virol

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Vaccine-induced B cells differentiate along two pathways. The follicular pathway gives rise to germinal centers (GCs) that can take weeks to fully develop. The extrafollicular pathway gives rise to short-lived plasma cells (PCs) that can rapidly secrete protective antibodies within days of vaccination. Rabies virus (RABV) postexposure prophylaxis (PEP) requires rapid vaccine-induced humoral immunity for protection. Therefore, we hypothesized that targeting extrafollicular B cell responses for activation would improve the speed and magnitude of RABV PEP. To test this hypothesis, we constructed, recovered, and characterized a recombinant RABV-based vaccine expressing murine B cell activating factor (BAFF) (rRABV-mBAFF). BAFF is an ideal molecule to improve early pathways of B cell activation, as it links innate and adaptive immunity, promoting potent B cell responses. Indeed, rRABV-mBAFF induced a faster, higher antibody response in mice and enhanced survivorship in PEP settings compared to rRABV. Interestingly, rRABV-mBAFF and rRABV induced equivalent numbers of GC B cells, suggesting that rRABV-mBAFF augmented the extrafollicular B cell pathway. To confirm that rRABV-mBAFF modulated the extrafollicular pathway, we used a signaling lymphocytic activation molecule (SLAM)-associated protein (SAP)-deficient mouse model. In response to antigen, SAP-deficient mice form extrafollicular B cell responses but do not generate GCs. rRABV-mBAFF induced similar anti-RABV antibody responses in SAP-deficient and wild-type mice, demonstrating that BAFF modulated immunity through the extrafollicular and not the GC B cell pathway. Collectively, strategies that manipulate pathways of B cell activation may facilitate the development of a single-dose RABV vaccine that replaces current complicated and costly RABV PEP.IMPORTANCE Effective RABV PEP is currently resource-and cost-prohibitive in regions of the world where RABV is most prevalent. In order to diminish the requirements for rabies immunoglobulin (RIG) and multiple vaccinations for effective prevention of clinical rabies, a more rapidly protective vaccine is needed. This work presents a successful approach to rapidly generate antibody-secreting PCs in response to vaccination by targeting the extrafollicular B cell pathway. We demonstrate that the improved early antibody responses induced by rRABV-mBAFF confer improved protection against RABV in a PEP model. Significantly, activation of the early extrafollicular B cell pathway, such as that demonstrated here, could improve the efficacy of vaccines targeting other pathogens against which rapid protection would decrease morbidity and mortality.

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Section: Discussionsupporting

confidence: 81%

mentioning

confidence: 99%

Targeting Vaccine-Induced Extrafollicular Pathway of B Cell Differentiation Improves Rabies Postexposure Prophylaxis

Haley

Tzvetkov

Meuwissen

et al. 2017

J Virol

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“…BAFF is a cytokine for the differentiation and survival of follicular B cells along with humoral response potentiation (23). As previously suggested (24)(25)(26), BAFF might induce beneficial humoral immune responses to vaccine antigens. IP-10 is a chemokine for attraction of human monocytes, activated T cells, and NK cells (27,28).…”

Section: Discussionmentioning

confidence: 90%

Phase II Study of Personalized Peptide Vaccination for Previously Treated Advanced Colorectal Cancer

Kibe

Yutani

Motoyama

et al. 2014

Cancer Immunology Research

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The prognosis of advanced colorectal cancer (aCRC) remains poor, and development of new therapeutic approaches, including immunotherapy, is needed urgently. Herein we report on our phase II study of personalized peptide vaccination (PPV) in 60 previously treated patients with aCRC, who had failed at least one regimen of standard chemotherapy and/or targeted therapy. For PPV, a maximum of four HLA-matched peptides were individually selected from a pool of 31 different peptide candidates based on preexisting host immunity, and administered subcutaneously without severe adverse events. Boosting of IgG and cytotoxic T lymphocyte (CTL) responses specific to the administered peptides was observed in 49% and 63%, respectively, of the patients, who completed the first cycles of six vaccinations. Median overall survival (OS) time was 498 days, with 1-and 2-year survival rates of 53% and 22%, respectively. Multivariate Cox regression analysis of prevaccination factors showed that plasma IL6, IP-10, and BAFF levels were significantly prognostic for OS [hazard ratio (HR), 1.508, P ¼ 0.043; HR, 1.579, P ¼ 0.024; HR, 0.509, P ¼ 0.002, respectively]. In addition, increased peptide-specific CTL responses after vaccination were significantly predictive of favorable OS (HR, 0.231; P ¼ 0.021), suggesting a causal relationship between biologic and clinical efficacy of PPV. On the basis of the safety profile and potential clinical efficacy, we believe that clinical trials of PPV would be warranted for previously treated patients with aCRC.

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“…For this response the B cell requires a co-stimulatory signal by Transmembrane Activator and CAML Interactor (TACI), which is a Tumor Necrosis Factor (TNF) receptor homolog that binds to B Lymphocyte Stimulator (BLyS) and a proliferation inducing ligand (APRIL) [11,12]. A recent report using BLyS covalently attached to a protein antigen showed a strong adjuvant effect with production of IgG1, IgG2a, IgG2b, IgG3, and no IgA [13]. Splenic B cells, which respond with T-independent antigens are in the marginal zone and are presented antigen by dendritic cells with TACI and BLyS co-stimulation.…”

Section: Introductionmentioning

confidence: 99%

Cancer vaccines and carbohydrate epitopes

Heimburg-Molinaro

Lum

Vijay

et al. 2011

Vaccine

217

152

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Tumor-associated carbohydrate antigens (TACA) result from the aberrant glycosylation that is seen with transformation to a tumor cell. The carbohydrate antigens that have been found to be tumor-associated include the mucin related Tn, Sialyl Tn, and Thomsen-Friedenreich antigens, the blood group Lewis related LewisY, Sialyl LewisX and Sialyl LewisA, and LewisX, (also known as stage-specific embryonic antigen-1, SSEA-1), the glycosphingolipids Globo H and stage-specific embryonic antigen-3 (SSEA-3), the sialic acid containing glycosphingolipids, the gangliosides GD2, GD3, GM2, fucosyl GM1, and Neu5GcGM3, and polysialic acid. Recent developments have furthered our understanding of the T-independent type II response that is seen in response to carbohydrate antigens. The selection of a vaccine target antigen is based on not only the presence of the antigen in a variety of tumor tissues but also on the role this antigen plays in tumor growth and metastasis. These roles for TACAs are being elucidated. Newly acquired knowledge in understanding the T-independent immune response and in understanding the key roles that carbohydrates play in metastasis are being applied in attempts to develop an effective vaccine response to TACAs. The role of each of the above mentioned carbohydrate antigens in cancer growth and metastasis and vaccine attempts using these antigens will be described.

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Enhanced immunogenicity of pneumococcal surface adhesin A (PsaA) in mice via fusion to recombinant human B lymphocyte stimulator (BLyS)

Cited by 14 publications

References 55 publications

Targeting Vaccine-Induced Extrafollicular Pathway of B Cell Differentiation Improves Rabies Postexposure Prophylaxis

Targeting Vaccine-Induced Extrafollicular Pathway of B Cell Differentiation Improves Rabies Postexposure Prophylaxis

Phase II Study of Personalized Peptide Vaccination for Previously Treated Advanced Colorectal Cancer

Cancer vaccines and carbohydrate epitopes

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