Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Immunity, Cellular , Immunity, Humoral , VaccinationABSTRACT
BACKGROUND: Homologous and heterologous SARS-CoV-2 vaccinations yield different spike protein-directed humoral and cellular immune responses. This study aimed to explore their currently unknown interdependencies. METHODS: COV-ADAPT is a prospective, observational cohort study of 417 healthcare workers who received vaccination with homologous ChAdOx1 nCoV-19, homologous BNT162b2 or with heterologous ChAdOx1 nCoV-19/BNT162b2. We assessed humoral (anti-spike-RBD-IgG, neutralizing antibodies, and avidity) and cellular (spike-induced T-cell interferon-γ release) immune responses in blood samples up to 2 weeks before (T1) and 2-12 weeks following secondary immunization (T2). RESULTS: Initial vaccination with ChAdOx1 nCoV-19 resulted in lower anti-spike-RBD-IgG compared with BNT162b2 (70 ± 114 vs. 226 ± 279 BAU/ml, p < .01) at T1. Booster vaccination with BNT162b2 proved superior to ChAdOx1 nCoV-19 at T2 (anti-spike-RBD-IgG: ChAdOx1 nCoV-19/BNT162b2 2387 ± 1627 and homologous BNT162b2 3202 ± 2184 vs. homologous ChAdOx1 nCoV-19 413 ± 461 BAU/ml, both p < .001; spike-induced T-cell interferon-γ release: ChAdOx1 nCoV-19/BNT162b2 5069 ± 6733 and homologous BNT162b2 4880 ± 7570 vs. homologous ChAdOx1 nCoV-19 1152 ± 2243 mIU/ml, both p < .001). No significant differences were detected between BNT162b2-boostered groups at T2. For ChAdOx1 nCoV-19, no booster effect on T-cell activation could be observed. We found associations between anti-spike-RBD-IgG levels (ChAdOx1 nCoV-19/BNT162b2 and homologous BNT162b2) and T-cell responses (homologous ChAdOx1 nCoV-19 and ChAdOx1 nCoV-19/BNT162b2) from T1 to T2. Additionally, anti-spike-RBD-IgG and T-cell response were linked at both time points (all groups combined). All regimes yielded neutralizing antibodies and increased antibody avidity at T2. CONCLUSIONS: Interdependencies between humoral and cellular immune responses differ between common SARS-CoV-2 vaccination regimes. T-cell activation is unlikely to compensate for poor humoral responses.
Subject(s)
COVID-19 Vaccines , COVID-19 , Immunity, Cellular , Immunity, Humoral , Antibodies, Neutralizing , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines/immunology , ChAdOx1 nCoV-19 , Humans , Immunoglobulin G , Interferon-gamma , Prospective Studies , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , VaccinationABSTRACT
The bisphosphonate zoledronic acid (ZA) significantly reduces complications of bone metastasis by inhibiting resident macrophages, the osteoclasts. Recent clinical trials indicate additional anti-metastatic effects of ZA outside the bone. However, which step of metastasis is influenced and whether thisis due to directtoxicity on cancer cells or inhibition of the tumor promoting microenvironment, is unknown. In particular, tumor-associated and resident macrophages support each step of organ metastasis and could be a crucial target of ZA. Thus, we comparatively investigate the ZA effects on: i) different types of macrophages, ii) on breast cancer cells but also iii) on macrophage-induced invasion. We demonstrate that ZA concentrations reflecting the plasma level affected viability of human macrophages, murine bone marrow-derived macrophages as well as their resident brain equivalents, the microglia, while it did not influence the tested cancer cells. However, the effects on the macrophages subsequently reduced the macrophage/microglia-induced invasiveness of the cancer cells. In line with this, manipulation of microglia by ZA in organotypic brain slice cocultures reduced the tissue invasion by carcinoma cells. The characterization of human macrophages after ZA treatment revealed a phenotype/response shift, in particular after external stimulation. In conclusion, we show that therapeutic concentrations of ZA affect all types of macrophages but not the cancer cells. Thus, anti-metastatic effects of ZA are predominantly caused by modulating the microenvironment. Most importantly, our findings demonstrate that ZA reduced microglia-assisted invasion of cancer cells to the brain tissue, indicating a potential therapeutic role in the prevention of cerebral metastasis.
Subject(s)
Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Diphosphonates/pharmacology , Imidazoles/pharmacology , Macrophages/drug effects , Macrophages/pathology , Microglia/drug effects , Microglia/pathology , Animals , Breast Neoplasms/metabolism , Cell Communication/drug effects , Cell Line, Tumor , Cell Proliferation , Coculture Techniques , Female , Humans , MCF-7 Cells , Macrophages/metabolism , Matrix Metalloproteinases/metabolism , Mice , Tumor Microenvironment/drug effects , Zoledronic AcidABSTRACT
Fluorescent staining using optical brighteners (diaminostilbenes) affords the semispecific and rapid detection of fungal elements in clinical specimens. After yielding a first hint of mycosis, the identification of the involved fungal genus is often desirable in cases when culture proves unsuccessful. In such cases, immunohistochemistry or in situ hybridisation may further the diagnosis with respect to establish an appropriate therapy.
Subject(s)
Aspergillus fumigatus/isolation & purification , Candida albicans/isolation & purification , Mycoses/diagnosis , Mycoses/microbiology , Rhizopus/isolation & purification , Staining and Labeling/methods , Stilbenes , Aspergillosis/diagnosis , Aspergillosis/microbiology , Candidiasis/diagnosis , Candidiasis/microbiology , Coloring Agents , Fluorescence , Fluorescent Dyes , Humans , Mucormycosis/diagnosis , Mucormycosis/microbiologyABSTRACT
We report on the recurrence of Candida albicans among yeast isolates from our university hospital. After a decline in occurrence which coincided with the onset of the use of fluconazole, the fraction of C. albicans recovered and at present has reached the pre-fluconazole level. No permanent rise of C. glabrata or C. krusei has been observed.
