Cytotoxic T cell vaccination with PLGA microspheres interferes with influenza A virus replication in the lung and suppresses the infectious disease

Herrmann, Valerie L.; Hartmayer, Carmen; Planz, Oliver; Groettrup, Marcus

doi:10.1016/j.jconrel.2015.08.019

Cited by 20 publications

(13 citation statements)

References 42 publications

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“…The particulate vaccines trials to advance the potential of nanotechnology based approach demand the evaluation of a candidate vaccines in multiple animal models, including in pig before choosing the right model for translational studies to revolutionize vaccine development against highly demanding respiratory infections like influenza in humans [80]. In mice using a welldefined and highly conserved IAV-derived CTLs peptides encapsulated in PLGA microspheres induction of strong CTLs response and complete protection against a viral challengewas achieved [81]. But our data in pigs showed that induction of strong CTLs response by using PLGA-KAg vaccine has helped to reduce the clinical flu symptoms, substantially cleared the challenged heterologous virus from the lungs, but failed to reduce the nasal viral shedding;…”

Section: Discussionmentioning

confidence: 99%

Biodegradable nanoparticle delivery of inactivated swine influenza virus vaccine provides heterologous cell-mediated immune response in pigs

Dhakal

Hiremath

Bondra

et al. 2017

Journal of Controlled Release

102

131

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Swine influenza virus (SwIV) is one of the important zoonotic pathogens. Current flu vaccines have failed to provide cross-protection against evolving viruses in the field. Poly(lactic-co-glycolic acid) (PLGA) is a biodegradable FDA approved polymer and widely used in drug and vaccine delivery. In this study, inactivated SwIV H1N2 antigens (KAg) encapsulated in PLGA nanoparticles (PLGA-KAg) were prepared, which were spherical in shape with 200 to 300nm diameter, and induced maturation of antigen presenting cells in vitro. Pigs vaccinated twice with PLGA-KAg via intranasal route showed increased antigen specific lymphocyte proliferation and enhanced the frequency of T-helper/memory and cytotoxic T cells (CTLs) in peripheral blood mononuclear cells (PBMCs). In PLGA-KAg vaccinated and heterologous SwIV H1N1 challenged pigs, clinical flu symptoms were absent, while the control pigs had fever for four days. Grossly and microscopically, reduced lung pathology and viral antigenic mass in the lung sections with clearance of infectious challenge virus in most of the PLGA-KAg vaccinated pig lung airways were observed. Immunologically, PLGA-KAg vaccine irrespective of not significantly boosting the mucosal antibody response, it augmented the frequency of IFN-γ secreting total T cells, T-helper and CTLs against both H1N2 and H1N1 SwIV. In summary, inactivated influenza virus delivered through PLGA-NPs reduced the clinical disease and induced cross-protective cell-mediated immune response in a pig model. Our data confirmed the utility of a pig model for intranasal particulate flu vaccine delivery platform to control flu in humans.

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Section: Discussionmentioning

confidence: 99%

Biodegradable nanoparticle delivery of inactivated swine influenza virus vaccine provides heterologous cell-mediated immune response in pigs

Dhakal

Hiremath

Bondra

et al. 2017

Journal of Controlled Release

102

131

View full text Add to dashboard Cite

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“…and the supernatant was collected. The virus titers of the homogenates were determined using the AVICEL® plaque assay 28 , 29 .…”

Section: Methodsmentioning

confidence: 99%

Targeting intracellular signaling as an antiviral strategy: aerosolized LASAG for the treatment of influenza in hospitalized patients

Scheuch¹,

Canisius²,

Nocker³

et al. 2018

Emerging Microbes & Infections

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Influenza has been a long-running health problem and novel antiviral drugs are urgently needed. In pre-clinical studies, we demonstrated broad antiviral activity of D, L-lysine-acetylsalicylate glycine (LASAG) against influenza virus (IV) in cell culture and protection against lethal challenge in mice. LASAG is a compound with a new antiviral mode of action. It inhibits the NF-κB signal transduction module that is essential for IV replication. Our goal was to determine whether aerosolized LASAG would also show a therapeutic benefit in hospitalized patients suffering from severe influenza. The primary endpoint was time to alleviation of clinical influenza symptoms. The primary analysis was based on the modified intention-to-treat (MITT) population. This included all patients with confirmed influenza virus infection who received at least one treatment. The per protocol (PP) analysis set included all subjects from the MITT population who underwent at least 13 inhalations. In the MITT group, 48 (41.7%) participants (29 LASAG; 19 placebo) had severe influenza. The mean time to symptom alleviation was 56.2 h in the placebo group and 43.0 h in the LASAG group. The PP set consisted of 41 patients (24 LASAG; 17 placebo). The mean time to symptom alleviation in the LASAG group (38.3 h; P = 0.0365) was lower than that in the placebo group (56.2 h). In conclusion, LASAG improved the time to alleviation of influenza symptoms in hospitalized patients. The present phase II proof-of-concept (PoC) study demonstrates that targeting an intra-cellular signaling pathway using aerosolized LASAG improves the time to symptom alleviation compared to standard treatment.

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“…Apart from generation of anti-tumor responses, we additionally could demonstrate the preeminence of PLGA MS in infectious diseases. PLGA MS encapsulated Influenza virus matrix M1 peptide together with CpG induced potent anti-viral CTL responses and protected against Influenza A infection (168).…”

Section: Anti-tumor Responses To Immunotherapy With Plga Particlesmentioning

confidence: 99%

Harnessing Dendritic Cells for Poly (D,L-lactide-co-glycolide) Microspheres (PLGA MS)—Mediated Anti-tumor Therapy

2019

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With emerging success in fighting off cancer, chronic infections, and autoimmune diseases, immunotherapy has become a promising therapeutic approach compared to conventional therapies such as surgery, chemotherapy, radiation therapy, or immunosuppressive medication. Despite the advancement of monoclonal antibody therapy against immune checkpoints, the development of safe and efficient cancer vaccine formulations still remains a pressing medical need. Anti-tumor immunotherapy requires the induction of antigen-specific CD8+ cytotoxic T lymphocyte (CTL) responses which recognize and specifically destroy tumor cells. Due to the crucial role of dendritic cells (DCs) in initiating anti-tumor immunity, targeting tumor antigens to DCs has become auspicious in modern vaccine research. Over the last two decades, micron- or nanometer-sized particulate delivery systems encapsulating tumor antigens and immunostimulatory molecules into biodegradable polymers have shown great promise for the induction of potent, specific and long-lasting anti-tumor responses in vivo . Enhanced vaccine efficiency of the polymeric micro/nanoparticles has been attributed to controlled and continuous release of encapsulated antigens, efficient targeting of antigen presenting cells (APCs) such as DCs and subsequent induction of CTL immunity. Poly (D, L-lactide- co -glycolide) (PLGA), as one of these polymers, has been extensively studied for the design and development of particulate antigen delivery systems in cancer therapy. This review provides an overview of the current state of research on the application of PLGA microspheres (PLGA MS) as anti-tumor cancer vaccines in activating and potentiating immune responses attempting to highlight their potential in the development of cancer therapeutics.

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Cytotoxic T cell vaccination with PLGA microspheres interferes with influenza A virus replication in the lung and suppresses the infectious disease

Cited by 20 publications

References 42 publications

Biodegradable nanoparticle delivery of inactivated swine influenza virus vaccine provides heterologous cell-mediated immune response in pigs

Biodegradable nanoparticle delivery of inactivated swine influenza virus vaccine provides heterologous cell-mediated immune response in pigs

Targeting intracellular signaling as an antiviral strategy: aerosolized LASAG for the treatment of influenza in hospitalized patients

Harnessing Dendritic Cells for Poly (D,L-lactide-co-glycolide) Microspheres (PLGA MS)—Mediated Anti-tumor Therapy

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