在人类中,季节性流感病毒引起流行病。禽流感病毒特别令人关注,因为它们可以感染多个物种并导致不可预测的严重疾病。因此,迫切需要一种针对所有流感毒株提供保护的通用流感疫苗。环GMP-AMP(cGAMP)是亚单位疫苗的一种有前途的佐剂,通过干扰素基因刺激因子(STING)途径促进I型干扰素的产生。cGAMP在缩醛化葡聚糖(Ace-DEX)微粒(MPs)中的包封增强了其细胞内递送。在这项研究中,计算优化的广义反应抗原(COBRA)方法用于产生H1、H3和H5候选疫苗。在小鼠中评价用cGAMPAce-DEXMPs配制的单价和多价COBRAHA疫苗的保护性抗体应答。cGAMPs佐剂化的COBRAHA疫苗在疫苗接种后引发强大的抗原特异性抗体。与无佐剂或空白MPs的COBRAHA疫苗组相比,cGAMP增强了COBRAHA疫苗引起的HAI活性。cGAMPs佐剂化的单价或多价COBRAHA疫苗之间的HAI活性没有显着差异。与没有佐剂或空白MP的COBRA疫苗组相比,cGAMPs佐剂化的COBRA疫苗组具有更高的抗原特异性IgG2a结合滴度。用cGAMPs配制的COBRA疫苗减轻了由流感病毒攻击引起的疾病并降低了小鼠的肺部病毒滴度。因此,COBRA疫苗加cGAMP是一种有前途的通用流感疫苗,可引发针对人类季节性和大流行前毒株的保护性免疫应答.
目的:流感病毒引起严重的呼吸道疾病,尤其是年轻人和老年人。需要下一代流感疫苗来预防新的流感变种。这份报告使用了一种有前途的佐剂,循环GMP-AMP(cGAMP),通过改进的流感血凝素候选物增强引发的抗体,并防止流感病毒感染。总的来说,在流感疫苗中添加佐剂是改进疫苗的有效方法。
In humans, seasonal influenza viruses cause epidemics. Avian influenza viruses are of particular concern because they can infect multiple species and lead to unpredictable and severe disease. Therefore, there is an urgent need for a universal influenza vaccine that provides protection against all influenza strains. The cyclic GMP-AMP (cGAMP) is a promising adjuvant for subunit vaccines, which promotes type I interferons\' production through the stimulator of interferon genes (STING) pathway. The encapsulation of cGAMP in acetalated dextran (Ace-DEX) microparticles (MPs) enhances its intracellular delivery. In this study, the Computationally Optimized Broadly Reactive Antigen (
COBRA) methodology was used to generate H1, H3, and H5 vaccine candidates. Monovalent and multivalent
COBRA HA vaccines formulated with cGAMP Ace-DEX MPs were evaluated in mice for protective antibody responses. cGAMP MPs adjuvanted COBRA HA vaccines elicited robust antigen-specific antibodies following vaccination. Compared with COBRA HA vaccine groups with no adjuvant or blank MPs, the cGAMP MPs enhanced HAI activity elicited by
COBRA HA vaccines. The HAI activity was not significantly different between cGAMP MPs adjuvanted monovalent or multivalent COBRA HA vaccines. The cGAMP MPs adjuvanted COBRA vaccine groups had higher antigen-specific IgG2a-binding titers than the
COBRA vaccine groups with no adjuvant or blank MPs. The COBRA vaccines formulated with cGAMP MPs mitigated diseases caused by influenza viral challenge and decreased pulmonary viral titers in mice. Therefore, the formulation of
COBRA vaccines plus cGAMP MPs is a promising universal influenza vaccine that elicits protective immune responses against human seasonal and pre-pandemic strains.
OBJECTIVE: Influenza viruses cause severe respiratory disease, particularly in the very young and the elderly. Next-generation influenza vaccines are needed to protect against new influenza variants. This report used a promising adjuvant, cyclic GMP-AMP (cGAMP), to enhance the elicited antibodies by an improved influenza hemagglutinin candidate and protect against influenza virus infection. Overall, adding adjuvants to influenza vaccines is an effective method to improve vaccines.