Rochester General Hospital Research Institute, Rochester, NY 14621, USA.
Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, NY 14642, USA.
Vaccine. 2019 Jul 26;37(32):4637-4645. doi: 10.1016/j.vaccine.2017.07.027. Epub 2017 Jul 26.
Moraxella catarrhalis (Mcat) is a frequent pathogen of acute otitis media (AOM) in young children. Here we prospectively assessed naturally-induced serum antibodies to four Mcat vaccine candidate proteins in stringently defined otitis prone (sOP) and non-otitis prone (NOP) children age 6-36months old following nasopharyngeal (NP) colonization, at onset of AOM and convalescence from AOM.
Serum IgG and IgM antibody against recombinant Mcat proteins, oligopeptide permease A (OppA), outer membrane protein (OMP) CD, hemagglutinin (Hag), and PilA clade 2 (PilA2), were quantitated by ELISA.
During NP colonization by Mcat all four antigens were immunogenic in both sOP and NOP children. However, sOP children had lower antibody responses than NOP children across age 6-36months, similar to our findings for protein vaccine candidates of Streptococcus pneumoniae (Spn) and Nontypeable Haemophilus influenzae (NTHi). sOP children displayed a later and lower peak of antibody rise than NOP children for all four antigens during NP colonization of Mcat. The age-dependent increase of antibody ranked as OppA>Hag5-9>OMP CD>PilA2 in both sOP and NOP children. Lower serum antibody levels to the Mcat antigens were measured in sOP compared to NOP children at the onset of AOM. We did not find a consistent significant increase of antibody at the convalescence phase after an AOM event.
sOP children is a highly vulnerable population that mount lower serum antibody responses to Mcat candidate vaccine proteins compared to NOP children during asymptomatic NP carriage and at onset of AOM.
粘膜炎莫拉氏菌(Mcat)是婴幼儿急性中耳炎(AOM)的常见病原体。在此,我们前瞻性评估了严格定义的易患中耳炎(sOP)和非易患中耳炎(NOP)6-36 月龄儿童在鼻咽(NP)定植后、AOM 发作时和 AOM 恢复期时针对 4 种 Mcat 疫苗候选蛋白的天然诱导血清抗体。
通过 ELISA 定量检测针对重组 Mcat 蛋白、寡肽透酶 A(OppA)、外膜蛋白(OMP)CD、血凝素(Hag)和 PilA 亚群 2(PilA2)的血清 IgG 和 IgM 抗体。
在 Mcat 通过 NP 定植期间,sOP 和 NOP 儿童均对所有 4 种抗原产生免疫应答。然而,sOP 儿童在 6-36 月龄时的抗体反应低于 NOP 儿童,这与我们对肺炎链球菌(Spn)和非典型流感嗜血杆菌(NTHi)的蛋白疫苗候选物的研究结果相似。在 Mcat 通过 NP 定植期间,sOP 儿童的抗体峰值出现时间晚且低于 NOP 儿童。4 种抗原在 sOP 和 NOP 儿童中均呈现随年龄增长而增加的抗体趋势,排名为 OppA>Hag5-9>OMP CD>PilA2。与 NOP 儿童相比,sOP 儿童在 AOM 发作时的 Mcat 抗原血清抗体水平较低。我们未发现 AOM 事件后恢复期的抗体水平有一致的显著增加。
sOP 儿童是一个高度脆弱的人群,与 NOP 儿童相比,在无症状 NP 携带和 AOM 发作期间,针对 Mcat 候选疫苗蛋白的血清抗体反应较低。