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1.
Sci Adv ; 8(3): eabj9815, 2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-35044832

RESUMO

Safe and effective vaccines are needed to end the COVID-19 pandemic. Here, we report the preclinical development of a lipid nanoparticle­formulated SARS-CoV-2 mRNA vaccine, PTX-COVID19-B. PTX-COVID19-B was chosen among three candidates after the initial mouse vaccination results showed that it elicited the strongest neutralizing antibody response against SARS-CoV-2. Further tests in mice and hamsters indicated that PTX-COVID19-B induced robust humoral and cellular immune responses and completely protected the vaccinated animals from SARS-CoV-2 infection in the lung. Studies in hamsters also showed that PTX-COVID19-B protected the upper respiratory tract from SARS-CoV-2 infection. Mouse immune sera elicited by PTX-COVID19-B vaccination were able to neutralize SARS-CoV-2 variants of concern, including the Alpha, Beta, Gamma, and Delta lineages. No adverse effects were induced by PTX-COVID19-B in either mice or hamsters. Based on these results, PTX-COVID19-B was authorized by Health Canada to enter clinical trials in December 2020 with a phase 2 clinical trial ongoing.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas Sintéticas/imunologia , Vacinas de mRNA/imunologia , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Contagem de Linfócito CD4 , Linfócitos T CD8-Positivos/imunologia , COVID-19/imunologia , Vacinas contra COVID-19/efeitos adversos , Canadá , Linhagem Celular , Cricetinae , Avaliação Pré-Clínica de Medicamentos , Feminino , Células HEK293 , Humanos , Imunidade Celular/imunologia , Imunidade Humoral/imunologia , Lipossomos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Nanopartículas , Glicoproteína da Espícula de Coronavírus/genética , Células Th1/imunologia
2.
J Forensic Leg Med ; 16(6): 346-9, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19573847

RESUMO

We report a case of an elderly demented woman who died of a mitral rheumatic valvular disease in the context of multiple injuries and from elder abuse. History from police investigation indicated that the deceased was found collapsed on the floor in her bedroom for several days prior to death by her son who did not initiate medical care. Autopsy revealed a frail elderly woman with Alzheimer's disease and evidence of multiple healing sublethal blunt impact injuries of the face, mouth, neck, upper chest, and extremities. In addition, there was unwashed dirt encrusted skin, urine/fecal staining of skin and clothing, dirty overgrown toenails, and matting of the hair. This constellation of findings supports the medical diagnosis of elder abuse with neglect. However, the immediate cause of death was the left-sided congestive heart failure from mitral rheumatic valvular disease. Although the underlying cause of death was related to the chronic cardiac condition, the physical abuse and neglect was considered significant contributing factors to death, since physiologically the injuries and lack of medical treatment was thought to have hastened death by exacerbating the underlying heart disease. This case underscores the need for the forensic pathologist to consider contextual variables and sublethal injuries in cases were the causal interpretations benefit from a more holistic approach. Otherwise, cases like such as the one reported can go unnoticed and certified as a simple natural death.


Assuntos
Doença de Alzheimer/complicações , Contusões/patologia , Abuso de Idosos , Idoso Fragilizado , Valva Mitral/patologia , Cardiopatia Reumática/patologia , Idoso , Traumatismos Faciais/patologia , Fezes , Feminino , Patologia Legal , Insuficiência Cardíaca/patologia , Humanos , Higiene , Desnutrição/complicações , Valva Mitral/microbiologia , Urina
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