Rivera-Hernandez Tania, Carnathan Diane G, Richter Johanna, Marchant Patrick, Cork Amanda J, Elangovan Gayathiri, Henningham Anna, Cole Jason N, Choudhury Biswa, Moyle Peter M, Toth Istvan, Batzloff Michael R, Good Michael F, Agarwal Paresh, Kapoor Neeraj, Nizet Victor, Silvestri Guido, Walker Mark J
Consejo Nacional de Humanidades Ciencia y Tecnología, Unidad de Investigación Médica en Inmunoquímica, Hospital de Especialidades del Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico.
School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia.
Vaccines (Basel). 2024 Apr 4;12(4):382. doi: 10.3390/vaccines12040382.
Vaccine development against group A (GAS) has gained traction in the last decade, fuelled by recognition of the significant worldwide burden of the disease. Several vaccine candidates are currently being evaluated in preclinical and early clinical studies. Here, we investigate two conjugate vaccine candidates that have shown promise in mouse models of infection. Two antigens, the J8 peptide from the conserved C-terminal end of the M protein, and the group A carbohydrate lacking -acetylglucosamine side chain (ΔGAC) were each conjugated to arginine deiminase (ADI), an anchorless surface protein from GAS. Both conjugate vaccine candidates combined with alum adjuvant were tested in a non-human primate (NHP) model of pharyngeal infection. High antibody titres were detected against J8 and ADI antigens, while high background antibody titres in NHP sera hindered accurate quantification of ΔGAC-specific antibodies. The severity of pharyngitis and tonsillitis signs, as well as the level of GAS colonisation, showed no significant differences in NHPs immunised with either conjugate vaccine candidate compared to NHPs in the negative control group.
在过去十年中，鉴于认识到A群链球菌（GAS）在全球造成的重大疾病负担，针对该病菌的疫苗研发工作受到了广泛关注。目前，有几种候选疫苗正在进行临床前和早期临床研究评估。在此，我们研究了两种在感染小鼠模型中显示出前景的结合疫苗候选物。两种抗原，即来自M蛋白保守C末端的J8肽和缺乏N-乙酰葡糖胺侧链的A群碳水化合物（ΔGAC），分别与精氨酸脱氨酶（ADI）偶联，ADI是一种来自GAS的无锚定表面蛋白。两种结合疫苗候选物与明矾佐剂联合，在咽部感染的非人类灵长类动物（NHP）模型中进行了测试。检测到针对J8和ADI抗原的高抗体滴度，而NHP血清中的高背景抗体滴度阻碍了对ΔGAC特异性抗体的准确定量。与阴性对照组的NHP相比，用任何一种结合疫苗候选物免疫的NHP中，咽炎和扁桃体炎体征的严重程度以及GAS定植水平均无显著差异。
