Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, USA.
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, USA.
Vaccine. 2019 Aug 14;37(35):4937-4946. doi: 10.1016/j.vaccine.2019.07.031. Epub 2019 Jul 15.
Urinary tract infection (UTI) is most frequently caused by uropathogenic Escherichia coli (UPEC). Our laboratory has been developing an experimental vaccine targeting four UPEC outer membrane receptors involved in iron acquisition - IreA, FyuA, IutA, and Hma - to elicit protection against UTI. These vaccine targets are all expressed in humans during UTI. In the murine model, high titers of antigen-specific serum IgG or bladder IgA correlate with protection against transurethral challenge with UPEC. Our aim was to measure levels of pre-existing serum antibodies to UTI vaccine antigens in our target population. To accomplish this, we obtained sera from 64 consenting female patients attending a clinic for symptoms of cystitis. As a control, we also collected sera from 20 healthy adult male donors with no history of UTI. Total IgG and antigen-specific IgG titers were measured by ELISA. Of the 64 female patients, 29 had significant bacteriuria (>10 cfu/ml urine) and uropathogenic E. coli (UPEC). Thirty-five patients had non-significant bacteriuria (<10 cfu/ml). Antigen-specific IgG titers did not correlate with the presence or absence of the gene encoding the antigen in the infecting strain (when present), but rather titers were proportional to prevalence of genes encoding antigens among representative collections of UPEC isolates. Surprisingly, we obtained similar results when sera from healthy male patients without history of UTI were tested. Thus, unvaccinated adults have non-protective levels of pre-existing antibodies to UTI vaccine antigens, establishing an important baseline for our target population. This suggests that a UTI vaccine would need to boost pre-existing humoral responses beyond these background levels to protect from infection.
尿路感染（UTI）最常由尿路致病性大肠杆菌（UPEC）引起。我们的实验室一直在开发一种针对四种参与铁摄取的 UPEC 外膜受体的实验性疫苗——IreA、FyuA、IutA 和 Hma，以引发对 UTI 的保护。这些疫苗靶点在人类 UTI 期间都有表达。在小鼠模型中，针对抗原的高滴度血清 IgG 或膀胱 IgA 与经尿道挑战 UPEC 的保护作用相关。我们的目的是测量目标人群中针对 UTI 疫苗抗原的预先存在的血清抗体水平。为了实现这一目标，我们从 64 名因膀胱炎症状就诊的同意参与的女性患者中获得了血清。作为对照，我们还从 20 名没有 UTI 病史的健康成年男性供体中收集了血清。通过 ELISA 测量总 IgG 和抗原特异性 IgG 滴度。在 64 名女性患者中，29 名有明显的菌尿症（>10cfu/ml 尿液）和尿路致病性大肠杆菌（UPEC）。35 名患者有非显著菌尿症（<10cfu/ml）。抗原特异性 IgG 滴度与感染株中编码抗原的基因的存在与否无关（存在时），而是与代表性 UPEC 分离株中编码抗原的基因的流行率成正比。令人惊讶的是，当测试没有 UTI 病史的健康男性患者的血清时，我们得到了类似的结果。因此，未接种疫苗的成年人对 UTI 疫苗抗原具有无保护作用的预先存在的抗体水平，为我们的目标人群建立了一个重要的基线。这表明 UTI 疫苗需要将预先存在的体液反应提升到这些背景水平以上，以防止感染。
