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1.
Nat Commun ; 15(1): 6007, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39030218

RESUMO

An influenza vaccine approach that overcomes the problem of viral sequence diversity and provides long-lived heterosubtypic protection is urgently needed to protect against pandemic influenza viruses. Here, to determine if lung-resident effector memory T cells induced by cytomegalovirus (CMV)-vectored vaccines expressing conserved internal influenza antigens could protect against lethal influenza challenge, we immunize Mauritian cynomolgus macaques (MCM) with cynomolgus CMV (CyCMV) vaccines expressing H1N1 1918 influenza M1, NP, and PB1 antigens (CyCMV/Flu), and challenge with heterologous, aerosolized avian H5N1 influenza. All six unvaccinated MCM died by seven days post infection with acute respiratory distress, while 54.5% (6/11) CyCMV/Flu-vaccinated MCM survived. Survival correlates with the magnitude of lung-resident influenza-specific CD4 + T cells prior to challenge. These data demonstrate that CD4 + T cells targeting conserved internal influenza proteins can protect against highly pathogenic heterologous influenza challenge and support further exploration of effector memory T cell-based vaccines for universal influenza vaccine development.


Assuntos
Linfócitos T CD4-Positivos , Citomegalovirus , Vírus da Influenza A Subtipo H1N1 , Vacinas contra Influenza , Macaca fascicularis , Animais , Vacinas contra Influenza/imunologia , Vacinas contra Influenza/administração & dosagem , Linfócitos T CD4-Positivos/imunologia , Vírus da Influenza A Subtipo H1N1/imunologia , Citomegalovirus/imunologia , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , Virus da Influenza A Subtipo H5N1/imunologia , Pulmão/imunologia , Pulmão/virologia , Pulmão/patologia , Vetores Genéticos/genética , Vetores Genéticos/imunologia , Masculino , Feminino , Células T de Memória/imunologia , Memória Imunológica/imunologia , Vacinação
2.
iScience ; 26(10): 107830, 2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37766976

RESUMO

Highly pathogenic avian influenza A H5N1 viruses cause high mortality in humans and have pandemic potential. Effective vaccines and treatments against this threat are urgently needed. Here, we have refined our previously established model of lethal H5N1 infection in cynomolgus macaques. An inhaled aerosol virus dose of 5.1 log10 plaque-forming unit (pfu) induced a strong febrile response and acute respiratory disease, with four out of six macaques succumbing after challenge. Vaccination with three doses of adjuvanted seasonal quadrivalent influenza vaccine elicited low but detectable neutralizing antibody to H5N1. All six vaccinated macaques survived four times the 50% lethal dose of aerosolized H5N1, while four of six unvaccinated controls succumbed to disease. Although vaccination did not protect against severe influenza, vaccinees had reduced respiratory dysfunction and lower viral load in airways compared to controls. We anticipate that our macaque model will play a vital role in evaluating vaccines and antivirals against influenza pandemics.

3.
Gynecol Oncol Rep ; 19: 59-61, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28203626

RESUMO

•Leiomyomatosis following laparoscopic hysterectomy with morcellation is reported.•Parasitic myomas grow in a benign fashion but may be fatal depending on location.•Fibroids are a contraindication for laparoscopic hysterectomy with morcellation.•Containment bags may address intraperitoneal spillage of malignant tissue.

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