Antibody induction by Group B streptococcal vaccines for protection against fungal infections

 描述(申请人提供)：侵袭性真菌感染(IFI)的发病率很高，一旦这些机会性病原体站稳脚跟，IFI就很难治疗。医院获得性医院感染的发病率迅速上升，这可能会对卫生保健产生越来越大的影响。使IFIS的严重性更加严重的是相对缺乏抗真菌药物，出现了对三氮唑耐药的真菌 菌株是为数不多的几类有效的抗真菌药物之一，而且缺乏任何获得许可的抗真菌疫苗。该项目的长期目标是提供新的主动疫苗接种和被动保护战略，为有IFI风险的人员提供更优化的预防和治疗。我们提出了一种新的方法，即用烟曲霉和其他真菌与细菌共享的表位表达免疫原进行免疫接种。这一策略将绕过对表面真菌抗原的免疫反应的低响应性，这通常导致在真菌感染中缺乏保护性免疫。这种针对IFI的主动免疫的方法是基于以下发现：(I)用整个热致死链球菌株免疫小鼠可诱导对侵袭性曲霉病的保护；(Ii)抗A。烟雾菌抗体是通过结合疫苗在人类身上诱导产生的，这种结合疫苗已被用于接种人类对链球菌感染的疫苗。预防性结合疫苗的再利用及多菌种保护IFI的被动单抗的可用性 将产生很大的影响，并为有IFI风险或患有IFI的患者提供亟需的治疗。

 DESCRIPTION (provided by applicant): The morbidity associated with invasive fungal infections (IFIs) is high and IFIs are highly intractable to treatment once these opportunistic pathogens gain a foothold. There is a rapidly rising incidence in hospital- acquired nosocomial infections which are likely have an increasing impact on health care. Compounding the serious nature of IFIs is the relative lack of antifungal drugs, the emergence of triazole-resistant fungal strains, one of the few classes of effective anti-fungal agents, and the lack of any licensed anti-fungal vaccine. The long-term goal of this project is to provide new active vaccination and passive protection strategies that provide more optimal prevention and treatment for personnel at risk for IFI. We are proposing a novel approach that involves vaccination with immunogens expressing epitopes shared by Aspergillus fumigatus and other fungi with bacteria. This strategy will circumvent the low responsivity of the immune response to surface fungal antigens which normally leads to a lack of protective immunity in fungal infections. This approach, to develop active immunity against IFI, is based on findings that (i) immunization of mice with whole heat-killed strains of streptococci induced protection against invasive aspergillosis and (ii) anti-A. fumigatus Abs are induced in humans by conjugate vaccines that have been used to vaccinate humans against streptococcal infections. Repurposing of prophylactic conjugate vaccines and availability of passive monoclonal antibodies for protection against IFI by multiple fungal species would have a high impact and provide much needed treatments for patients at risk for, or suffering from IFIs.