RESUMO
Developing new influenza vaccines with improved performance and easier administration routes hinges on defining correlates of protection. Vaccine-elicited cellular correlates of protection for influenza in humans have not yet been demonstrated. A phase-2 double-blind randomized placebo and active (inactivated influenza vaccine) controlled study provides evidence that a human-adenovirus-5-based oral influenza vaccine tablet (VXA-A1.1) can protect from H1N1 virus challenge in humans. Mass cytometry characterization of vaccine-elicited cellular immune responses identified shared and vaccine-type-specific responses across B and T cells. For VXA-A1.1, the abundance of hemagglutinin-specific plasmablasts and plasmablasts positive for integrin α4ß7, phosphorylated STAT5, or lacking expression of CD62L at day 8 were significantly correlated with protection from developing viral shedding following virus challenge at day 90 and contributed to an effective machine learning model of protection. These findings reveal the characteristics of vaccine-elicited cellular correlates of protection for an oral influenza vaccine.
Assuntos
Imunidade , Vacinas contra Influenza/imunologia , Influenza Humana/imunologia , Vacinação , Método Duplo-Cego , Humanos , Imunidade Celular , Imunização , Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A , Influenza Humana/prevenção & controle , Selectina L/metabolismo , Fator de Transcrição STAT5/metabolismo , Linfócitos T , Vacinas de Produtos Inativados/imunologia , Eliminação de Partículas ViraisRESUMO
BACKGROUND: Influenza places a significant burden on global health and economics. Individual case management and public health efforts to mitigate the spread of influenza are both strongly impacted by our ability to accurately and efficiently detect influenza viruses in clinical samples. Therefore, it is important to understand the performance characteristics of available assays to detect influenza in a variety of settings. We provide the first report of relative performance between two products marketed to streamline detection of influenza virus in the context of a highly controlled volunteer influenza challenge study. METHODS: Nasopharyngeal swab samples were collected during a controlled A/California/2009/H1N1 influenza challenge study and analyzed for detection of virus shedding using a validated qRT-PCR (qPCR) assay, a sample-to-answer qRT-PCR device (BioMerieux BioFire FilmArray RP), and an immunoassay based rapid test kit (Quidel QuickVue Influenza A + B Test). RESULTS: Relative to qPCR, the sensitivity and specificity of the BioFire assay was 72.1% [63.7-79.5%, 95% confidence interval (CI)] and 93.5% (89.3-96.4%, 95% CI) respectively. For the QuickVue rapid test the sensitivity was 8.5% (4.8-13.7%, 95% CI) and specificity was 99.2% (95.6-100%, 95% CI). CONCLUSION: Relative to qPCR, the BioFire assay had superior performance compared to rapid test in the context of a controlled influenza challenge study.
Assuntos
Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza B/genética , Influenza Humana/diagnóstico , Técnicas de Diagnóstico Molecular/normas , Reação em Cadeia da Polimerase em Tempo Real/normas , Experimentação Humana , Humanos , Influenza Humana/virologia , Técnicas de Diagnóstico Molecular/métodos , Nasofaringe/virologia , Kit de Reagentes para Diagnóstico/normas , Reação em Cadeia da Polimerase em Tempo Real/métodos , Sensibilidade e Especificidade , Eliminação de Partículas Virais , VoluntáriosRESUMO
Influenza is a significant cause of morbidity and mortality worldwide. Here we show changes in the abundance and activation states of more than 50 immune cell subsets in 35 individuals over 11 time points during human A/California/2009 (H1N1) virus challenge monitored using mass cytometry along with other clinical assessments. Peak change in monocyte, B cell, and T cell subset frequencies coincided with peak virus shedding, followed by marked activation of T and NK cells. Results led to the identification of CD38 as a critical regulator of plasmacytoid dendritic cell function in response to influenza virus. Machine learning using study-derived clinical parameters and single-cell data effectively classified and predicted susceptibility to infection. The coordinated immune cell dynamics defined in this study provide a framework for identifying novel correlates of protection in the evaluation of future influenza therapeutics.
Assuntos
Vírus da Influenza A Subtipo H1N1/imunologia , Influenza Humana/imunologia , Células Matadoras Naturais/imunologia , Ativação Linfocitária , Linfócitos T/imunologia , Feminino , Humanos , MasculinoRESUMO
BACKGROUND: Recurrent vulvar lymphangitis secondary to pelvic lymphadenectomy and radiation therapy can be a vexing clinical dilemma. CASE: A 55-year-old woman was initially treated with radical hysterectomy and 1 postoperative radiotherapy for cervical carcinoma in 1984. In 1987 she developed persistent vulvar, leg, and ankle edema; chronic vulvar pain; and recurrent vulvar cellulitis, which were ultimately attributed to group B Streptococcus. Despite long-term antibiotic therapy and compression stockings, the cellulitis was intractable. In June 2006 the patient underwent a bilateral simple vulvectomy with preservation of the clitoris and insertion of bilateral subcutaneous Jackson-Pratt drains. Her postoperative culture results revealed normal vaginal flora. CONCLUSION: The patient's wounds healed very well, and she has had no further episodes of vulvitis or lymphangitis. The management of recurrent infections involving lymphedema can be difficult and cause complicated clinical issues.