Preclinical evaluation of a synthetic peptide vaccine against SARS-CoV-2 inducing multiepitopic and cross-reactive humoral neutralizing and cellular CD4 and CD8 responses.

Identification of relevant epitopes is crucial for the development of subunit peptide vaccines inducing neutralizing and cellular immunity against SARS-CoV-2. Our aim was the characterization of epitopes in the receptor-binding domain (RBD) of SARS-CoV-2 spike (S) protein to generate a peptide vaccine. Epitope mapping using a panel of 10 amino acid overlapped 15-mer peptides covering region 401-515 from RBD did not identify linear epitopes when tested with sera from infected individuals or from RBD-immunized mice. However, immunization of mice with these 15-mer peptides identified four peptides located at region 446-480 that induced antibodies recognizing the peptides and RBD/S1 proteins. Immunization with peptide 446-480 from S protein formulated with Freund's adjuvant or with CpG oligodeoxinucleotide/Alum induced polyepitopic antibody responses in BALB/c and C56BL/6J mice, recognizing RBD (titres of 3 × 104-3 × 105, depending on the adjuvant) and displaying neutralizing capacity (80-95% inhibition capacity; p < 0.05) against SARS-CoV-2. Murine CD4 and CD8T-cell epitopes were identified in region 446-480 and vaccination experiments using HLA transgenic mice suggested the presence of multiple human T-cell epitopes. Antibodies induced by peptide 446-480 showed broad recognition of S proteins and S-derived peptides belonging to SARS-CoV-2 variants of concern. Importantly, vaccination with peptide 446-480 or with a cyclic version of peptide 446-488 containing a disulphide bridge between cysteines 480 and 488, protected humanized K18-hACE2 mice from a lethal dose of SARS-CoV-2 (62.5 and 75% of protection; p < 0.01 and p < 0.001, respectively). This region could be the basis for a peptide vaccine or other vaccine platforms against Covid-19.

Adoptive T-cell therapy with CD45RA-depleted donor in the treatment of cytomegalovirus disease in immunocompromised non-transplant patients.

Cytomegalovirus (CMV) infections can induce severe complications in immunosuppressed patients. Currently, ganciclovir represents the preferred treatment option; however, in patients with resistance or toxicity related to ganciclovir, the therapeutic options are limited.Cellular immunity plays an important role in the control of viral infections. Adoptive T-cell therapy can contribute to recovering immunological function in immunosuppressed patients. Selective T-cell depletion targeting CD45RA enhances early T-cell recovery and can represent a salvage therapy. In this study, an immunocompromised non-transplanted patient with CMV disease and toxicity to conventional therapy was successfully treated by adoptive transfer of CD45RA-depleted T-cells.

Intracavitary and Systemic Daptomycin for Successful Treatment of a Postpneumonectomy Intrathoracic Infection.

Treatment of an infected postpneumonectomy cavity is very difficult. We present a patient with an infection of a postpneumonectomy cavity by Staphylococcus epidermidis treated with local daptomycin for different dwell times, maintaining high antibiotic levels above the MIC. Clinical and microbiological cure were achieved successfully.

Non-O1 Vibrio cholerae inguinal skin and soft tissue infection with bullous skin lesions in a patient with a penis squamous cell carcinoma.

Vibrio spp. is a pathogen rarely isolated in cancer patients, and in most cases it is associated with haematological diseases. Cutaneous manifestations of this organism are even rarer. We report a case of Non-O1 Vibrio cholerae inguinal skin and soft tissue infection presenting bullous skin lesions in a young type II diabetic patient with a penis squamous cell carcinoma having a seawater exposure history.

Anticardiolipin antibodies in chronic viral hepatitis. Do they have clinical consequences?

Antiphospholipid antibodies are a heterogeneous group of acquired autoantibodies that react with anionic phospholipids, such as cardiolipin. Anticardiolipin antibodies (ACAs) are frequently found in patients with systemic lupus erythematosus and other autoimmune disorders and can react with the phospholipid alone or bound to the cofactor beta2-glycoprotein-I. This latter form of cofactor-dependent ACAs is strongly associated with the occurrence of thrombotic events. ACAs have been observed to occur in both chronic hepatitis B and chronic hepatitis C as well as in other viral infections and in neoplastic diseases. In viral infection, ACAs are generally cofactor independent and may represent an epiphenomenon of the infection. Some studies, however, have found an increased incidence of thrombotic disorders in patients with chronic hepatitis C virus (HCV) who manifest ACA positivity suggesting that the presence of these autoantibodies may predispose to thrombosis in specific HCV-infected patients. In conclusion, ACAs are commonly found in patients with chronic viral infection but their pathogenetic role and the mechanisms that stimulate their production have not yet been clarified.