Blocking of α1ß1 and α2ß1 adhesion molecules inhibits eosinophil migration through human lung microvascular endothelial cell monolayer.

INTRODUCTION: In cell trafficking to the airways in asthma, among integrins the most important are those containing α4 and ß2 subunits. We have previously shown that also blocking of collagen receptors, α1ß1 and α2ß1 integrins, inhibits transmigration of eosinophils of asthmatic subjects through a monolayer of skin microvascular endothelial cells seeded on collagen IV coated inserts. However, it was not clear whether this observation was limited to asthma or depended on the type of microvascular cell and collagen IV used as a base. MATERIALS & METHODS: In the current study we performed a transmigration assay using human lung microvascular endothelial cells seeded directly on a plastic surface as a base and blood cells isolated from 12 representatives of each of two groups, asthmatics and healthy donors, by gradient centrifugation, followed by immunomagnetic negative separation of eosinophils. Isolated eosinophils and peripheral blood mononuclear cells (PBMC) were inhibited by snake venom-derived integrin antagonists including viperistatin and VP12, as inhibitors of α1ß1 and α2ß1 integrin, respectively, and VLO5 and VLO4, as inhibitors of α4ß1 and α5ß1 integrin, respectively. RESULTS: All snake venom-derived anti-adhesive proteins were effective in inhibiting eosinophil transmigration, whilst only VLO5 and VLO4 reduced PBMC mobility in this assay. This observation was similar in both groups of subjects studied. DISCUSSION: α1ß1 and α2ß1 integrins could be involved in transmigration of eosinophil to the inflammatory site. Migratory inhibition was observed in asthma subjects as well as in healthy donors, and did not depend on origin of endothelial cells or the extracellular matrix component used as a base.

Effectiveness and Safety of SARS-CoV-2 Vaccination in HIV-Infected Patients-Real-World Study.

The development of COVID-19 vaccines has been a triumph of biomedical research. However, there are still challenges, including assessment of their immunogenicity in high-risk populations, including PLWH. In the present study, we enrolled 121 PLWH aged >18 years, that were vaccinated against COVID-19 in the Polish National Vaccination Program. Patients filled in questionnaires regarding the side effects of vaccination. Epidemiological, clinical, and laboratory data were collected. The efficacy of COVID-19 vaccines was evaluated with an ELISA that detects IgG antibodies using a recombinant S1 viral protein antigen. The interferon-gamma release assay (IGRA) was applied to quantitate interferon-gamma (IFN-γ) to assess cellular immunity to SARS-CoV-2. In total, 87 patients (71.9%) received mRNA vaccines (BNT162b2-76 (59.5%), mRNA-1273- 11 (9.1%)). A total of 34 patients (28.09%) were vaccinated with vector-based vaccines (ChAdOx Vaxzevria- 20 (16.52%), Ad26.COV2.S- 14 (11.6%)). A total of 95 (78.5%) of all vaccinated patients developed a protective level of IgG antibodies. Only eight PLWH (6.6%) did not develop cellular immune response. There were six patients (4.95%) that did not develop a cellular and humoral response. Analysis of variance proved that the best humoral and cellular response related to the administration of the mRNA-1273 vaccine. COVID-19 vaccines were found to be immunogenic and safe in PLWH. Vaccination with mRNA vaccines were related to better humoral and cellular responses.