The newborn immune system is characterized by diminished immune responses that leave infants vulnerable to virus-mediated disease and make vaccination more challenging. Optimal vaccination strategies for influenza A virus (IAV) in newborns should result in robust levels of protective antibodies, including those with broad reactivity to combat the variability in IAV strains across seasons. The stem region of the hemagglutinin (HA) molecule is a target of such antibodies. Using a nonhuman primate model, we investigate the capacity of newborns to generate and maintain antibodies to the conserved stem region following vaccination. We find adjuvanting an inactivated vaccine with the TLR7/8 agonist R848 is effective in promoting sustained HA stem-specific IgG. Unexpectedly, HA stem-specific antibodies were generated with a distinct kinetic pattern compared to the overall response. Administration of R848 was associated with increased influenza-specific T follicular helper cells as well as Tregs with a less suppressive phenotype, suggesting adjuvant impacts multiple cell types that have the potential to contribute to the HA-stem response.

新生儿免疫系统的特点是免疫反应减弱，使婴儿容易感染病毒介导的疾病，并使疫苗接种更具挑战性。新生儿 A 型流感病毒 (IAV) 的最佳疫苗接种策略应产生高水平的保护性抗体，包括具有广泛反应性以对抗 IAV 跨季节变异的抗体。血凝素 (HA) 分子的干区是此类抗体的靶标。使用非人灵长类动物模型，我们研究了新生儿在接种疫苗后产生和维持针对保守干区域的抗体的能力。我们发现用 TLR7/8 激动剂 R848 辅助灭活疫苗可有效促进持续的 HA 干特异性 IgG。不料，与整体反应相比，HA 干特异性抗体的产生具有明显的动力学模式。R848 的施用与流感特异性 T 滤泡辅助细胞以及具有较少抑制表型的 Tregs 的增加有关，表明佐剂影响多种细胞类型，这些细胞类型有可能促进 HA 干细胞反应。