RESUMO
Rapid development of COVID-19 vaccines has helped mitigating SARS-CoV-2 spread, but more equitable allocation of vaccines is necessary to limit the global impact of the COVID-19 pandemic and the emergence of additional variants of concern. We have developed a COVID-19 vaccine candidate based on Newcastle disease virus (NDV) that can be manufactured at high yields in embryonated eggs. Here, we show that the NDV vector expressing an optimized spike antigen (NDV-HXP-S) is a versatile vaccine inducing protective antibody responses. NDV-HXP-S can be administered intramuscularly as inactivated vaccine or intranasally as live vaccine. We show that NDV-HXP-S GMP-produced in Vietnam, Thailand and Brazil is effective in the hamster model. Furthermore, we show that intramuscular vaccination with NDV-HXP-S reduces replication of tested variants of concerns in mice. The immunity conferred by NDV-HXP-S effectively counteracts SARS-CoV-2 infection in mice and hamsters.
RESUMO
The genetic diversity of influenza A viruses circulating in swine in Mexico complicates control efforts in animals and presents a threat to humans, as shown by influenza A(H1N1)pdm09 virus. To describe evolution of swine influenza A viruses in Mexico and evaluate strains for vaccine development, we sequenced the genomes of 59 viruses and performed antigenic cartography on strains from 5 regions. We found that genetic and antigenic diversity were particularly high in southeast Mexico because of repeated introductions of viruses from humans and swine in other regions in Mexico. We identified novel reassortant H3N2 viruses with genome segments derived from 2 different viruses that were independently introduced from humans into swine: pandemic H1N1 viruses and seasonal H3N2 viruses. The Mexico swine viruses are antigenically distinct from US swine lineages. Protection against these viruses is unlikely to be afforded by US virus vaccines and would require development of new vaccines specifically targeting these diverse strains.
Assuntos
Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H3N2/genética , Influenza Humana/virologia , Infecções por Orthomyxoviridae/virologia , Vírus Reordenados/genética , Animais , Antígenos Virais/imunologia , Humanos , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H3N2/imunologia , Vacinas contra Influenza/genética , Vacinas contra Influenza/imunologia , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , México , Infecções por Orthomyxoviridae/epidemiologia , Infecções por Orthomyxoviridae/prevenção & controle , SuínosRESUMO
Asia is considered an important source of influenza A virus (IAV) pandemics, owing to large, diverse viral reservoirs in poultry and swine. However, the zoonotic origins of the 2009 A/H1N1 influenza pandemic virus (pdmH1N1) remain unclear, due to conflicting evidence from swine and humans. There is strong evidence that the first human outbreak of pdmH1N1 occurred in Mexico in early 2009. However, no related swine viruses have been detected in Mexico or any part of the Americas, and to date the most closely related ancestor viruses were identified in Asian swine. Here, we use 58 new whole-genome sequences from IAVs collected in Mexican swine to establish that the swine virus responsible for the 2009 pandemic evolved in central Mexico. This finding highlights how the 2009 pandemic arose from a region not considered a pandemic risk, owing to an expansion of IAV diversity in swine resulting from long-distance live swine trade.
Assuntos
Evolução Molecular , Vírus da Influenza A Subtipo H1N1/genética , Influenza Humana/virologia , Infecções por Orthomyxoviridae/veterinária , Doenças dos Suínos/virologia , Zoonoses/virologia , Animais , Humanos , Vírus da Influenza A Subtipo H1N1/classificação , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Influenza Humana/epidemiologia , México , Infecções por Orthomyxoviridae/virologia , Pandemias , Análise de Sequência de DNA , Suínos , Doenças dos Suínos/epidemiologia , Zoonoses/epidemiologiaRESUMO
BACKGROUND: The ß adrenergic receptors (ADRB) are expressed in the ciliary body and trabecular meshwork, structures involved in aqueous humor production and outflow, respectively. ADRB are members of the adrenergic family of G-protein-coupled receptors. Topic ß blockers have a good local and systemic tolerance; they reduce the aqueous humor production and eye strain blocking the ADRB of the ciliary body and interfering with adenylate cyclase. However, the ocular hypotensive response is not the same in all patients and could be mediated by the polymorphisms of the ADRB genes. MATERIALS AND METHODS: Seventy-two healthy subjects were studied after treatment with topical betaxolol in both eyes. We analyzed ADRB1 and ADRB2 gene polymorphisms by PCR and automated DNA sequencing. RESULTS: There was statistically significant difference between baseline intraocular pressure (IOP) and final IOP of both eyes (baseline IOP 16.2 ± 1.2 - follow-up IOP 13.6 ± 2.0 (mean difference-2.5 ± 1.3, p < 0.001). Gly389 had a higher baseline IOP than Arg389 (17.0 ± 1.2 mmHg versus 16.0 ± 1.2 mmHg; p = 0.02), and conversely Arg389 had a greater magnitude of response than Gly389 to betaxolol therapy (-2.9 ± 1.1 mmHg versus -0.7 ± 0.4 mmHg; p < 0.001). Gln27 had a higher response than Glu27 (-2.7 ± 1.3 mmHg versus -1.9 ± 1.0; p = 0.02). CONCLUSION: Arg389 polymorphism of the ADRB1 gene and Gln27 polymorphism of the ADRB2 gene were associated with the hypotensive response to topic betaxolol in healthy Mexican volunteers.
Assuntos
Antagonistas de Receptores Adrenérgicos beta 1/administração & dosagem , Betaxolol/administração & dosagem , Pressão Intraocular/efeitos dos fármacos , Polimorfismo de Nucleotídeo Único , Receptores Adrenérgicos beta 1/genética , Receptores Adrenérgicos beta 2/genética , Administração Tópica , Adulto , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/uso terapêutico , Feminino , Frequência do Gene , Genótipo , Voluntários Saudáveis , Humanos , Pressão Intraocular/genética , Masculino , México , Pessoa de Meia-Idade , Hipotensão Ocular/induzido quimicamente , Hipotensão Ocular/genética , Soluções Oftálmicas , Reação em Cadeia da Polimerase , Tonometria OcularRESUMO
The current investigation, framed within the emotional cognitive science field, was conducted with three patients with major depression. They participated in a therapeutic process which involved EMDR (Eye Movement Desensitization and Reprocessing). Data were obtained in the clinical practice through a longitudinal one subject study design, including: emotional valence identification within affective priming experiments; and depressive emotional representation studies, the data of which was analyzed using multidimensional scaling. The first ones had the purpose of observing the therapeutic impact over the emotional cognitive bias mechanism regarding depresogenic words related to traumatic experiences; and the second, to analyze modifications on depressive schemata. The results showed that EMDR had a positive effect both on emotional cognitive processing and on long-term memory conceptual organization. In the discussion section, interesting remarks are made on the incorporation of emotional cognitive science tools to the EMDR clinical practice.