High-Throughput Profiling of Anti-Glycan Humoral Responses to SIV Vaccination and Challenge

Recent progress toward an HIV vaccine highlights both the potential of vaccines to end the AIDS pandemic and the need to boost efficacy by incorporating additional vaccine strategies. Although many aspects of the immune response can contribute to vaccine efficacy, the key factors have not been defined fully yet. A particular area that may yield new insights is anti-glycan immune responses, such as those against the glycan shield that HIV uses to evade the immune system. In this study, we used glycan microarray technology to evaluate anti-glycan antibody responses induced by SIV vaccination and infection in a non-human primate model of HIV infection. This comprehensive profiling of circulating anti-glycan antibodies found changes in anti-glycan antibody levels after both vaccination with the Ad5hr-SIV vaccine and SIV infection. Notably, SIV infection produced generalized declines in anti-glycan IgM antibodies in a number of animals. Additionally, some infected animals generated antibodies to the Tn antigen, which is a cryptic tumor-associated antigen exposed by premature termination of O-linked glycans; however, the Ad5hr-SIV vaccine did not induce anti-Tn IgG antibodies. Overall, this study demonstrates the potential contributions that glycan microarrays can make for HIV vaccine development.

HIV疫苗研发的最新进展，既彰显了疫苗终结艾滋病大流行的巨大潜力，也凸显了通过整合多元疫苗策略以提升疫苗效力的迫切需求。尽管免疫应答的诸多维度均可对疫苗效力产生助力，但核心影响因素尚未完全明确。其中一个有望带来全新认知的特定领域，是抗聚糖免疫应答，例如针对HIV用于逃避免疫系统的聚糖外壳的相关应答。本研究采用聚糖微阵列（glycan microarray）技术，在HIV感染的非人类灵长类动物模型中，评估了猴免疫缺陷病毒（SIV）疫苗接种与感染所诱导的抗聚糖抗体应答。对循环抗聚糖抗体的全面谱学分析发现，在接种Ad5hr-SIV疫苗以及SIV感染后，抗聚糖抗体水平均发生显著变化。值得注意的是，在部分受试动物中，SIV感染导致其抗聚糖免疫球蛋白M（IgM）抗体水平普遍下降。此外，部分感染动物产生了针对Tn抗原的抗体——该抗原是一种因O-连接聚糖提前终止合成而暴露的隐蔽肿瘤相关抗原；但Ad5hr-SIV疫苗并未诱导产生抗Tn免疫球蛋白G（IgG）抗体。综上，本研究证实了聚糖微阵列技术在HIV疫苗研发中具备的潜在应用价值。