Section for Molecular Biology and Immunology, Helminth Immunology Group, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
Research Department for Viral Zoonoses-One Health, Leibniz Institute for Experimental Virology, Hamburg, Germany.
PLoS One. 2022 Mar 31;17(3):e0266456. doi: 10.1371/journal.pone.0266456. eCollection 2022.
The world health organization estimates that more than a quarter of the human population is infected with parasitic worms that are called helminths. Many helminths suppress the immune system of their hosts to prolong their survival. This helminth-induced immunosuppression "spills over" to unrelated antigens and can suppress the immune response to vaccination against other pathogens. Indeed, several human studies have reported a negative correlation between helminth infections and responses to vaccinations. Using mice that are infected with the parasitic nematode Litomosoides sigmodontis as a model for chronic human filarial infections, we reported previously that concurrent helminth infection impaired the vaccination-induced protection against the human pathogenic 2009 pandemic H1N1 influenza A virus (2009 pH1N1). Vaccinated, helminth-infected mice produced less neutralizing, influenza-specific antibodies than vaccinated naïve control mice. Consequently helminth-infected and vaccinated mice were not protected against a challenge infection with influenza virus but displayed high virus burden in the lung and a transient weight loss. In the current study we tried to improve the vaccination efficacy using vaccines that are licensed for humans. We either introduced a prime-boost vaccination regimen using the non-adjuvanted anti-influenza vaccine Begripal or employed the adjuvanted influenza vaccine Fluad. Although both strategies elevated the production of influenza-specific antibodies and protected mice from the transient weight loss that is caused by an influenza challenge infection, sterile immunity was not achieved. Helminth-infected vaccinated mice still had high virus burden in the lung while non-helminth-infected vaccinated mice rapidly cleared the virus. In summary we demonstrate that basic improvements of influenza vaccination regimen are not sufficient to confer sterile immunity on the background of helminth-induced immunosuppression, despite amelioration of pathology i.e. weight loss. Our findings highlight the risk of failed vaccinations in helminth-endemic areas, especially in light of the ongoing vaccination campaign to control the COVID-19 pandemic.
世界卫生组织估计，超过四分之一的人口感染了寄生虫蠕虫，这些蠕虫被称为蠕虫。许多蠕虫会抑制宿主的免疫系统，以延长其生存时间。这种蠕虫引起的免疫抑制“溢出”到无关抗原上，并能抑制对其他病原体的疫苗接种的免疫反应。事实上，几项人类研究报告称，蠕虫感染与疫苗接种反应之间存在负相关。我们以前曾使用感染寄生线虫旋毛虫的小鼠作为慢性人类丝虫感染的模型，报道称，同时感染蠕虫会损害疫苗接种对人类致病的 2009 年大流行性 H1N1 流感 A 病毒（2009 pH1N1）的诱导保护。接种疫苗、感染蠕虫的小鼠产生的中和性、流感特异性抗体比接种疫苗的未感染对照小鼠少。因此，感染蠕虫和接种疫苗的小鼠不能免受流感病毒的挑战感染，但在肺部显示出高病毒载量和短暂的体重减轻。在当前的研究中，我们试图使用已获许可用于人类的疫苗来提高疫苗接种的效果。我们使用未佐剂的抗流感疫苗 Begripal 或使用佐剂流感疫苗 Fluad 引入了一种初级-加强免疫方案。尽管这两种策略都提高了流感特异性抗体的产生，并保护了小鼠免受流感挑战感染引起的短暂体重减轻，但并未实现无菌免疫。感染蠕虫的接种疫苗的小鼠肺部仍然有高病毒载量，而未感染蠕虫的接种疫苗的小鼠迅速清除了病毒。总之，我们证明，尽管改善了体重减轻等病理学，但在蠕虫引起的免疫抑制背景下，基本改进流感疫苗接种方案不足以提供无菌免疫。我们的发现突出了在蠕虫流行地区疫苗接种失败的风险，尤其是考虑到正在进行的疫苗接种运动来控制 COVID-19 大流行。
