Engineered Viruses as Vaccine Platforms

Folgori, Antonella; Capone, Stefania

doi:10.1007/978-94-007-4543-8_4

Cited by 3 publications

(3 citation statements)

References 109 publications

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“…Although there has clearly been some success to prevent infection with persisting viruses (i.e., hepatitis B virus, papilloma virus), vaccination as a whole has been unsuccessful in preventing persistent viral infections, including HIV, HCV, EBV and CMV. Current evidence suggests that numerically larger and multifunctional CD4 and CD8 T cell responses are associated with enhanced control of HIV and HCV replication and prevention of HCV persistence (33)(34)(35)(36)(37), suggesting that the efficacy of vaccination is dependent on the size and particularly the quality of the T cell responses it elicits. Thus, adjuvants and vaccines that quantitatively and qualitatively enhance immunity might be able to overcome the immune threshold that dictates viral clearance or persistence.…”

Section: Discussionmentioning

confidence: 99%

“…Splenocytes were stimulated for 5 h with 5 μg/mL of the MHC class II restricted LCMV-GP 61-80 or 2 μg/mL of the MHC class I restricted LCMV-NP 396-404 , GP [33][34][35][36][37][38][39][40][41] , or GP 276-286 peptide (all >99% pure; Synpep) in the presence of 50 U/mL recombinant murine IL-2 (R&D Systems) and 1 mg/mL brefeldin A (Sigma). Cells were stained for surface expression of CD4 (PE, APC, or Pacific Blue; clone RM4-5), CD8 (Pacific Blue; clone 53-6.7), IL-7Rα (APC; clone SB/199), Ly5.1 (APC or APC-Cy7; clone A20), or Thy1.2 (PE or PerCP; clone 30-H12).…”

Section: Methodsmentioning

confidence: 99%

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IL-10 directly suppresses CD4 but not CD8 T cell effector and memory responses following acute viral infection

Brooks

Walsh

Elsaesser

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

132

114

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Mounting effective T cell responses is critical for eliciting longlasting immunity following viral infection and vaccination. A multitude of inhibitory and stimulatory factors are induced following infection, and it is the compilation of these signals that quantitatively and qualitatively program the ensuing effector and memory T cell response. In response to lymphocytic choriomeningitis virus (LCMV) infection, the immunosuppressive cytokine IL-10 is rapidly up-regulated; however, how IL-10 is regulating what is often considered an "optimal" immune response is unclear. We demonstrate that IL-10 directly inhibits effector and memory CD4 T cell responses following an acutely resolved viral infection. Blockade of IL-10 enhanced the magnitude and the functional capacity of effector CD4 T cells that translated into increased and more effective memory responses. On the other hand, lack of IL-10 signaling did not impact memory CD8 T cell development. We propose that blockade of IL-10 may be an effective adjuvant to specifically enhance CD4 T cell immunity and protection following vaccination. Following infection, antigen-presenting cells (APC) present viral antigens to T cells and, in the context of multiple cell-based and soluble factors, instruct virus-specific T cells to proliferate and acquire multiple antiviral and immune-stimulatory effector functions. Virus-specific CD8 T cells acquire the ability to lyse virally infected cells both directly through cell to cell killing and indirectly through the secretion of cytokines, including TNFα and IFNγ (reviewed in ref. 1). Simultaneously, virus-specific CD4 T cells proliferate and produce immunostimulatory cytokines (such as IL-2) that help to orchestrate the direction of the immune response, sustain and program memory CD8 T cell differentiation, and provide help to B cells for antibody production (2). Following clearance of the infection, effector virus-specific CD4 and CD8 T cells contract and, through a complex differentiation program, generate a stable memory T cell population able to rapidly respond and clear future infections with the same or similar virus (3). Early IL-2 signals are important for secondary CD8 T cell responses, and, once formed, T cell memory is sustained via homeostatic signals including the cytokines IL-7 and IL-15 (4, 5). Yet it is still poorly understood how different factors interact to initially instruct distinct immune responses and how the factors and signals that a T cell initially encounters are integrated to program long-term memory differentiation. Thus, the interplay between positive and negative regulatory signals toward memory development is largely unclear.Viral replication triggers the production of multiple immune stimulatory factors that activate and program T cell responses. As a counterbalance, negative regulatory factors are also produced to control the magnitude of the antiviral immune response and attenuate T cell responses following viral clearance to prevent excessive immunopathology. Many immune and nonimmune cell types...

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

IL-10 directly suppresses CD4 but not CD8 T cell effector and memory responses following acute viral infection

Brooks

Walsh

Elsaesser

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

132

114

View full text Add to dashboard Cite

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“…Induction of strong transgene-specific immune responses and negligible anti-vector immunity are the prerequisites of efficient viral vector-based vaccines [ 1 , 2 , 3 ]. Recently, Orf virus (ORFV, Parapoxvirus ) was reported as a novel viral vector for the expression of various foreign antigens.…”

Section: Introductionmentioning

confidence: 99%

Orf Virus-Based Vaccine Vector D1701-V Induces Strong CD8+ T Cell Response against the Transgene but Not against ORFV-Derived Epitopes

et al. 2020

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The potency of viral vector-based vaccines depends on their ability to induce strong transgene-specific immune response without triggering anti-vector immunity. Previously, Orf virus (ORFV, Parapoxvirus) strain D1701-V was reported as a novel vector mediating protection against viral infections. The short-lived ORFV-specific immune response and the absence of virus neutralizing antibodies enables repeated immunizations and enhancement of humoral immune responses against the inserted antigens. However, only limited information exists about the D1701-V induced cellular immunity. In this study we employed major histocompatibility complex (MHC) ligandomics and immunogenicity analysis to identify ORFV-specific epitopes. Using liquid chromatography-tandem mass spectrometry we detected 36 ORFV-derived MHC I peptides, originating from various proteins. Stimulated splenocytes from ORFV-immunized mice did not exhibit specific CD8+ T cell responses against the tested peptides. In contrast, immunization with ovalbumin-expressing ORFV recombinant elicited strong SIINFEKL-specific CD8+ T lymphocyte response. In conclusion, our data indicate that cellular immunity to the ORFV vector is negligible, while strong CD8+ T cell response is induced against the inserted transgene. These results further emphasize the ORFV strain D1701-V as an attractive vector for vaccine development. Moreover, the presented experiments describe prerequisites for the selection of T cell epitopes exploitable for generation of ORFV-based vaccines by reverse genetics.

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