ABSTRACT
The COVID-19 pandemic and the need for additional safe, effective, and affordable vaccines gave new impetus into development of vaccine genetic platforms. Here we report the findings from the phase 1, first-in-human, dose-escalation study of COVID-eVax, a DNA vaccine encoding the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. Sixty-eight healthy adults received two doses of 0.5, 1, or 2 mg 28 days apart, or a single 2-mg dose, via intramuscular injection followed by electroporation, and they were monitored for 6 months. All participants completed the primary safety and immunogenicity assessments after 8 weeks. COVID-eVax was well tolerated, with mainly mild to moderate solicited adverse events (tenderness, pain, bruising, headache, and malaise/fatigue), less frequent after the second dose, and it induced an immune response (binding antibodies and/or T cells) at all prime-boost doses tested in up to 90% of the volunteers at the highest dose. However, the vaccine did not induce neutralizing antibodies, while particularly relevant was the T cell-mediated immunity, with a robust Th1 response. This T cell-skewed immunological response adds significant information to the DNA vaccine platform and should be assessed in further studies for its protective capacity and potential usefulness also in other therapeutic areas, such as oncology.
Subject(s)
COVID-19 , Vaccines, DNA , Adult , Humans , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Double-Blind Method , Pandemics/prevention & control , SARS-CoV-2 , Vaccines, DNA/adverse effectsABSTRACT
Colchicine, a long established anti-inflammatory agent now used in several rheumatologic conditions, acts by inhibiting microtubular polymerization, as it binds equimolarly to tubulin molecules. Cytoskeletal microtubules are crucial in processes of cell viability, such as mitosis and intracellular vesicle motility.Gastrointestinal side effects are quite common and often minor in nature or duration, whereas neuromuscular toxicity is rare. We report 2 cases of colchicine myopathy in the context of very different clinical settings.
Subject(s)
Colchicine/adverse effects , Muscular Diseases/chemically induced , Tubulin Modulators/adverse effects , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Adolescent , Arthritis, Gouty/drug therapy , Colchicine/metabolism , Colchicine/therapeutic use , Cytochrome P-450 CYP3A/metabolism , Familial Mediterranean Fever/drug therapy , Female , Humans , Male , Middle Aged , Muscle Weakness/chemically induced , Muscle Weakness/diagnosis , Muscular Diseases/diagnosis , Tubulin Modulators/metabolism , Tubulin Modulators/therapeutic useABSTRACT
Weber-Christian Disease (WCD), also known as relapsing febrile lobular non-suppurative panniculitis, is a rare condition characterized by recurrent subcutaneous inflammatory nodules in the adipose tissue in addition to fever, malaise and other systemic manifestations such as polyarthralgia and polymyalgia. The association with small vessel vasculitis has been rarely reported. We report here an unusual case of WCD associated with small vessels vasculitis also describing the efficacy of Cyclosporin A treatment.