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1.
BMJ Case Rep ; 14(12)2021 Dec 20.
Article in English | MEDLINE | ID: mdl-34930763

ABSTRACT

The Welsh Centre for Burns and Plastic Surgery is responsible for a population of 10 million people in Wales and England. We describe the use of biodegradable temporising matrix (BTM) in a large traumatic chest wound in a 23-year-old woman. BTM is a synthetic dermal substitute and has been utilised to achieve soft tissue coverage in complex wounds. This wound was sustained after the patient fell from a tractor into a large silage rake, resulting in injuries to her chest and limbs. Following meticulous debridement, her resulting full thickness skin defect measured 30 × 30 cm extending from the sternal notch to the upper abdomen, with bone, muscle and breast tissue exposure. The central chest area is complex to reconstruct due to the contours of the breasts and tendency to contracture following skin graft reconstruction. We demonstrate the first reported use of BTM for breast reconstruction, as far as we are aware.


Subject(s)
Absorbable Implants , Thoracic Injuries/surgery , England , Humans , Young Adult
2.
J Infect Dis ; 222(5): 807-819, 2020 08 04.
Article in English | MEDLINE | ID: mdl-31740938

ABSTRACT

BACKGROUND: Increasing evidence supports a critical role of CD8+ T-cell immunity against influenza. Activation of mucosal CD8+ T cells, particularly tissue-resident memory T (TRM) cells recognizing conserved epitopes would mediate rapid and broad protection. Matrix protein 1 (M1) is a well-conserved internal protein. METHODS: We studied the capacity of modified vaccinia Ankara (MVA)-vectored vaccine expressing nucleoprotein (NP) and M1 (MVA-NP+M1) to activate M1-specific CD8+ T-cell response, including TRM cells, in nasopharynx-associated lymphoid tissue from children and adults. RESULTS: After MVA-NP+M1 stimulation, M1 was abundantly expressed in adenotonsillar epithelial cells and B cells. MVA-NP+M1 activated a marked interferon γ-secreting T-cell response to M1 peptides. Using tetramer staining, we showed the vaccine activated a marked increase in M158-66 peptide-specific CD8+ T cells in tonsillar mononuclear cells of HLA-matched individuals. We also demonstrated MVA-NP+M1 activated a substantial increase in TRM cells exhibiting effector memory T-cell phenotype. On recall antigen recognition, M1-specific T cells rapidly undergo cytotoxic degranulation, release granzyme B and proinflammatory cytokines, leading to target cell killing. CONCLUSIONS: MVA-NP+M1 elicits a substantial M1-specific T-cell response, including TRM cells, in nasopharynx-associated lymphoid tissue, demonstrating its strong capacity to expand memory T-cell pool exhibiting effector memory T-cell phenotype, therefore offering great potential for rapid and broad protection against influenza reinfection.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , Influenza A Virus, H3N2 Subtype/immunology , Nucleocapsid Proteins/immunology , Viral Matrix Proteins/immunology , Viral Vaccines/immunology , Adenoids/cytology , Adenoids/immunology , Adolescent , Adult , CD8-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/physiology , Cell Degranulation , Cell Proliferation , Cells, Cultured , Child , Child, Preschool , Granzymes/metabolism , Humans , Immunity, Cellular , Immunologic Memory , Interferon-gamma/metabolism , Lymphocyte Activation , Lysosomal-Associated Membrane Protein 1/metabolism , Nasopharynx , Palatine Tonsil/cytology , Palatine Tonsil/immunology , Respiratory Mucosa/immunology , Vaccines, DNA , Young Adult
3.
J Virol ; 92(11)2018 06 01.
Article in English | MEDLINE | ID: mdl-29563292

ABSTRACT

There is increasing interest recently in developing intranasal vaccines against respiratory tract infections. The antibody response is critical for vaccine-induced protection, and T follicular helper cells (TFH) are considered important for mediating the antibody response. Most data supporting the role for TFH in the antibody response are from animal studies, and direct evidence from humans is limited, apart from the presence of TFH-like cells in blood. We studied the activation and induction of TFH and their role in the anti-influenza antibody response induced by a live-attenuated influenza vaccine (LAIV) in human nasopharynx-associated lymphoid tissue (NALT). TFH activation in adenotonsillar tissues was analyzed by flow cytometry, and anti-hemagglutinin (anti-HA) antibodies were examined following LAIV stimulation of tonsillar mononuclear cells (MNC). Induction of antigen-specific TFH by LAIV was studied by flow cytometry analysis of induced TFH and CD154 expression. LAIV induced TFH proliferation, which correlated with anti-HA antibody production, and TFH were shown to be critical for the antibody response. Induction of TFH from naive T cells by LAIV was shown in newly induced TFH expressing BCL6 and CD21, followed by the detection of anti-HA antibodies. Antigen specificity of LAIV-induced TFH was demonstrated by expression of the antigen-specific T cell activation marker CD154 upon challenge by H1N1 virus antigen or HA. LAIV-induced TFH differentiation was inhibited by BCL6, interleukin-21 (IL-21), ICOS, and CD40 signaling blocking, and that diminished anti-HA antibody production. In conclusion, we demonstrated the induction by LAIV of antigen-specific TFH in human NALT that provide critical support for the anti-influenza antibody response. Promoting antigen-specific TFH in NALT by use of intranasal vaccines may provide an effective vaccination strategy against respiratory infections in humans.IMPORTANCE Airway infections, such as influenza, are common in humans. Intranasal vaccination has been considered a biologically relevant and effective way of immunization against airway infection. The vaccine-induced antibody response is crucial for protection against infection. Recent data from animal studies suggest that one type of T cells, TFH, are important for the antibody response. However, data on whether TFH-mediated help for antibody production operates in humans are limited due to the lack of access to human immune tissue containing TFH In this study, we demonstrate the induction of TFH in human immune tissue, providing critical support for the anti-influenza antibody response, by use of an intranasal influenza vaccine. Our findings provide direct evidence that TFH play a critical role in vaccine-induced immunity in humans and suggest a novel strategy for promoting such cells by use of intranasal vaccines against respiratory infections.


Subject(s)
Antibodies, Viral/immunology , Hemagglutinins, Viral/immunology , Influenza A Virus, H1N1 Subtype/immunology , Influenza Vaccines/immunology , Influenza, Human/immunology , Lymphocyte Activation/immunology , T-Lymphocytes, Helper-Inducer/immunology , Vaccines, Attenuated/immunology , Administration, Intranasal , Adolescent , Adult , Antibody Formation/immunology , B-Lymphocytes/immunology , CD40 Antigens/antagonists & inhibitors , CD40 Ligand/biosynthesis , Cells, Cultured , Child , Child, Preschool , Humans , Immunity, Mucosal/immunology , Inducible T-Cell Co-Stimulator Protein/antagonists & inhibitors , Influenza, Human/prevention & control , Influenza, Human/virology , Interleukins/antagonists & inhibitors , Mucous Membrane/immunology , Nasopharynx/immunology , Proto-Oncogene Proteins c-bcl-6/antagonists & inhibitors , Proto-Oncogene Proteins c-bcl-6/biosynthesis , Receptors, Complement 3d/biosynthesis , Young Adult
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