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

 描述（由申请人提供）：侵袭性真菌感染（IFIs）相关的发病率较高，一旦这些机会致病菌获得立足点，IFIs治疗非常棘手。医院获得性医院感染的发病率迅速上升，这可能对医疗保健产生越来越大的影响。使IFIs的严重性质更加复杂的是抗真菌药物的相对缺乏，三唑耐药真菌的出现， 菌株，有效的抗真菌剂的少数类别之一，以及缺乏任何许可的抗真菌疫苗。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风险的人员提供更佳的预防和治疗。我们提出了一种新的方法，涉及免疫接种表达表位的烟曲霉和其他真菌与细菌共享。这种策略将避免对表面真菌抗原的免疫应答的低应答性，这通常导致真菌感染中缺乏保护性免疫。该方法开发针对IFI的主动免疫，基于以下发现：（i）用链球菌的全热灭活菌株免疫小鼠诱导针对侵袭性曲霉病的保护，以及（ii）抗A.烟曲霉Ab在人类中由已用于接种人类以抵抗链球菌感染的缀合疫苗诱导。预防性偶联疫苗的再利用和被动单克隆抗体的可用性，以保护免受多种真菌种属的IFI 将产生很大的影响，并为有IFIs风险或患有IFIs的患者提供急需的治疗。

 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.