Novel HLA-A2-restricted human metapneumovirus epitopes reduce viral titers in mice and are recognized by human T cells

Human metapneumovirus (HMPV) is a major cause of morbidity and mortality from acute lower respiratory tract illness, with most individuals seropositive by age five. Despite the presence of neutralizing antibodies, secondary infections are common and can be severe in young, elderly, and immunocompromised persons. Preclinical vaccine studies for HMPV have suggested a need for a balanced antibody and T cell immune response to enhance protection and avoid lung immunopathology. We infected transgenic mice expressing human HLA-A*0201 with HMPV and used ELISPOT to screen overlapping and predicted epitope peptides. We identified six novel HLA-A2 restricted CD8⁺ T cell (T_CD8) epitopes, with M_39–47 (M39) immunodominant. Tetramer staining detected M39-specific T_CD8 in lungs and spleen of HMPV-immune mice. Immunization with adjuvant-formulated M39 peptide reduced lung virus titers upon challenge. Finally, we show that T_CD8 from HLA-A*0201 positive humans recognize M39 by IFNγ ELISPOT and tetramer staining. These results will facilitate HMPV vaccine development and human studies.     

Recurrent respiratory papillomatosis in northern Sweden: Clinical characteristics and practical guidance

Conclusion: Recurrent respiratory papillomatosis (RRP) patients with high surgical treatment frequency (≥ 1/year, HF) were significantly younger and had a more widespread laryngeal disease compared to a low frequency treated group (< 1 treatment/year, LF). This study confirms the existence of a clinical RRP group, not primarily related to HPV sub-type, but more care-intensive and in need of more vigilant follow-up. Objectives: RRP is associated with high morbidity due to its influence on breathing and voice. The purpose of this study was to characterize RRP patients in northern Sweden and investigate possible predictor factors affecting therapeutic needs. Method: Patients from the regional referral area (northern Sweden) were categorized for age, disease duration, juvenile or adult onset, profile of disease development, number of surgical sessions in relation to disease duration, laryngeal deposition of papilloma, gender, and HPV sub-types, in order to identify patients with increased need for frequent surgical treatment. Results: The median age of the RRP patients (n = 48) was 44.5 years; 34 (71%) were males and 14 (29%) females, most were infected with HPV 6. Patients with high surgical treatment frequency/year were significantly younger and showed more widespread papillomatous vegetation in the larynx, compared to the low frequency treated group.     

Infección por el virus de la hepatitis C y nuevas estrategias de tratamiento

Hepatitis C is a major public health problem worldwide. This disease is caused by the hepatitis C virus, which is characterised by its genetic diversity. The infection is usually asymptomatic. However, between 60% and 80% of HCV-infected individuals will progress to chronic hepatitis, 20% to liver cirrhosis in the medium-to long-term and, each year, between 1% and 4% of these patients with cirrhosis will develop hepatocellular carcinoma (HCC). A Spanish consensus document has recently been drafted to diagnose hepatitis C in a single step, consisting of active investigation (antibodies and viremia) in a single sample, which according to the experts, would reduce the time to access treatment and avoid tracking losses. To definitively change the hepatitis C treatment paradigm, direct-acting antiviral drugs (DAAs) have been approved, whose development has been based on achieving cure rates close to 100% regardless of the genotype of the virus, ie, pangenotypes, with good tolerance and bioavailability. These drugs have constituted a real therapeutic revolution. Supplement information: This article is part of a supplement entitled «SEIMC External Quality Control Programme. Year 2016», which is sponsored by Roche, Vircell Microbiologists, Abbott Molecular and Francisco Soria Melguizo, S.A.© 2019 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosasy Microbiología Clínica. All rights reserved.     

AAV-CRISPR Gene Editing Is Negated by Pre-existing Immunity to Cas9

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Method development of immunoglobulin G purification from micro-volumes of human serum for untargeted and targeted proteomics-based antibody repertoire studies

Immunoglobulins (Igs) are major serum proteins which play important roles in immunity. Both untargeted and targeted proteomic workflows can be applied to investigate antigen-binding sites and the glycosylation profiles of Igs. For a more-comprehensive picture of IgG from human serum, we developed an IgG purification process and coupled the standardized method to untargeted and targeted proteomic workflows for IgG investigations. Parameters such as the type of purification beads, volume of the bead slurry, incubation conditions, and binding capacities were evaluated in this study. Only 2 μL of human serum was required for each sample. The performance of coupling the purification process to untargeted proteomics in the IgG analysis was evaluated by comparing normalized abundances of IgG subclass-specific peptides with quantification results from an ELISA. Pearson's correlation values were all >0.82. Targeted proteomic workflow was applied to serum samples from patients with autoimmune pancreatitis and from healthy controls, and the results corresponded to clinical findings that IgG4-related peptides/glycopeptides showed higher abundances in the diseased group. The developed IgG purification process is simple and requires small sample volume, and it can be coupled to targeted and untargeted proteomic workflows for clinical investigations in the future.     

Novel β-Coronavirus (SARS-CoV-2): Current and future aspects of pharmacological treatments

The novel coronavirus outbreak has reported to be rapidly spreading across the countries and becomes a foremost community health alarm. At present, no vaccine or specific drug is on hand for the treatment of this infectious disease. This review investigates the drugs, which are being evaluated and found to be effective against nCOVID-19 infection. A thorough literature search was performedon the recently published research papers in between January 2020 to May 2020, through various databases like “Science Direct”, “Google Scholar”, “PubMed”,“Medline”, “Web of Science”, and “World Health Organization (WHO)”. We reviewed and documented the information related with the current and future aspects for the management and cure of COVID-19. As of 21st July 2020 a total of 14,562,550 confirmed cases of coronavirus and 607,781 deaths have been reported world-wide. The main clinical feature of COVID-19 ranges from asymptomatic disease to mild lower respiratory tract illness to severe pneumonia, acute lung injury, acute respiratory distress syndrome (ARDS), multiple organ dysfunction, and death. The drugs at present used in COVID-19 patients and ongoing clinical trials focusing on drug repurposing of various therapeutic classes of drug e.g. antiviral, anti-inflammatory and/or immunomodulatory drugs along with adjuvant/supportive care. Many drugs on clinical trials shows effective results on preliminary scale and now used currently in patients. Adjuvant/supportive care therapy are used in patients to get the best results in order to minimize the short and long-term complications. However, further studies and clinical trials are needed on large scale of population to reach any firm conclusion in terms of its efficacy and safety.