RESUMEN
The underlying immunological mechanisms of immediate-type hypersensitivity reactions (HSR) to COVID-19 vaccines are poorly understood. We investigate the mechanisms of immediate-type hypersensitivity reactions to the Pfizer BNT162b2 vaccine and the response of antibodies to the polyethylene glycol (PEG)ylated lipid nanoparticle after two doses of vaccination. Sixty-seven participants, median age 35 and 77.3% females who tolerated two doses of the BNT162b2 vaccine (non-reactors), were subjected to various blood-sampling time points. A separate group of vaccine reactors (10 anaphylaxis and 37 anonymised tryptase samples) were recruited for blood sampling. Immunoglobulin (Ig)G, IgM and IgE antibodies to the BNT162b2 vaccine, biomarkers associated with allergic reaction, including tryptase for anaphylaxis, complement 5a(C5a), intercellular adhesion molecule 1 (ICAM-1) for endothelial activation and Interleukin (IL)-4, IL-10, IL-33, tumour necrosis factor (TNF) and monocyte chemoattractant protein (MCP-1), were measured. Basophil activation test (BAT) was performed in BNT162b2-induced anaphylaxis patients by flow cytometry. The majority of patients with immediate-type BNT162b2 vaccine HSR demonstrated raised C5a and Th2-related cytokines but normal tryptase levels during the acute reaction, together with significantly higher levels of IgM antibodies to the BNT162b2 vaccine (IgM 67.2 (median) vs. 23.9 AU/mL, p < 0.001) and ICAM-1 when compared to non-reactor controls. No detectable IgE antibodies to the BNT162b2 vaccine were found in these patients. The basophil activation tests by flow cytometry to the Pfizer vaccine, 1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol (DMG-PEG) and PEG-2000 were negative in four anaphylaxis patients. Acute hypersensitivity reactions post BNT162b2 vaccination suggest pseudo-allergic reactions via the activation of anaphylatoxins C5a and are independent of IgE-mechanisms. Vaccine reactors have significantly higher levels of anti-BNT162b2 IgM although its precise role remains unclear.
Asunto(s)
Vacunas contra la COVID-19/efectos adversos , COVID-19/complicaciones , COVID-19/prevención & control , SARS-CoV-2/inmunología , Trombosis de la Vena/etiología , Vacuna BNT162 , COVID-19/epidemiología , COVID-19/virología , Vacunas contra la COVID-19/administración & dosificación , Vacunas contra la COVID-19/inmunología , Manejo de la Enfermedad , Susceptibilidad a Enfermedades , Humanos , Incidencia , Vacunación/efectos adversos , Trombosis de la Vena/diagnóstico , Trombosis de la Vena/epidemiologíaAsunto(s)
Betacoronavirus , Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/epidemiología , Neumonía Viral/sangre , Neumonía Viral/epidemiología , Adulto , Factores de Edad , Antígenos CD/sangre , COVID-19 , China , Infecciones por Coronavirus/fisiopatología , Femenino , Humanos , Lactato Deshidrogenasas/sangre , Linfopenia , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/fisiopatología , SARS-CoV-2 , Singapur , TrombocitopeniaRESUMEN
Tuberculosis is the most common opportunistic infection in HIV-infected people living in developing countries and is believed to accelerate the progression of HIV disease. This effect may be mediated by increased immune activation. We measured levels of CD4 and CD8 T-lymphocyte activation and proliferation in control subjects, patients with HIV alone, TB alone and patients with HIV and TB co-infection. Our results indicate that TB (in the absence of HIV) increases T-lymphocyte proliferation but its effects are modest in comparison with the stimulation induced by HIV infection alone.
