PDF(Pubmed)
Abstract：
UNASSIGNED: Yersinia pestis is the etiological agent of plague, which can manifest as bubonic, septicemic, and/or pneumonic disease. Plague is a severe and rapidly progressing illness that can only be successfully treated with antibiotics initiated early after infection. There are no FDA-approved vaccines for plague, and some vaccine candidates may be less effective against pneumonic plague than bubonic plague. Y. pestis is not known to impact males and females differently in mechanisms of pathogenesis or severity of infection. However, one previous study reported sex-biased vaccine effectiveness after intranasal Y. pestis challenge. As part of developing a safe and effective vaccine, it is essential that potential sex differences are characterized.
UNASSIGNED: In this study we evaluated novel vaccines in male and female BALB/c mice using a heterologous prime-boost approach and monitored survival, bacterial load in organs, and immunological correlates. Our vaccine strategy consisted of two subcutaneous immunizations, followed by challenge with aerosolized virulent nonencapsulated Y. pestis. Mice were immunized with a combination of live Y. pestis pgm- pPst-Δcaf1, live Y. pestis pgm- pPst-Δcaf1/ΔyopD, or recombinant F1-V (rF1-V) combined with adjuvants.
UNASSIGNED: The most effective vaccine regimen was initial priming with rF1-V, followed by boost with either of the live attenuated strains. However, this and other strategies were more protective in female mice. Males had higher bacterial burden and differing patterns of cytokine expression and serum antibody titers. Male mice did not demonstrate synergy between vaccination and antibiotic treatment as repeatedly observed in female mice.
UNASSIGNED: This study provides new knowledge about heterologous vaccine strategies, sex differences in plague-vaccine efficacy, and the immunological factors that differ between male and female mice.
UNASSIGNED: In this study we evaluated novel vaccines in male and female BALB/c mice using a heterologous prime-boost approach and monitored survival, bacterial load in organs, and immunological correlates. Our vaccine strategy consisted of two subcutaneous immunizations, followed by challenge with aerosolized virulent nonencapsulated Y. pestis. Mice were immunized with a combination of live Y. pestis pgm- pPst-Δcaf1, live Y. pestis pgm- pPst-Δcaf1/ΔyopD, or recombinant F1-V (rF1-V) combined with adjuvants.
UNASSIGNED: The most effective vaccine regimen was initial priming with rF1-V, followed by boost with either of the live attenuated strains. However, this and other strategies were more protective in female mice. Males had higher bacterial burden and differing patterns of cytokine expression and serum antibody titers. Male mice did not demonstrate synergy between vaccination and antibiotic treatment as repeatedly observed in female mice.
UNASSIGNED: This study provides new knowledge about heterologous vaccine strategies, sex differences in plague-vaccine efficacy, and the immunological factors that differ between male and female mice.
摘要：
鼠疫耶尔森氏菌是鼠疫的病原体，可以表现为泡泡，败血症，和/或肺炎。鼠疫是一种严重且快速发展的疾病，只能在感染后早期使用抗生素成功治疗。没有FDA批准的鼠疫疫苗，一些候选疫苗对肺鼠疫的效果可能不如腺鼠疫。已知鼠疫耶尔森氏菌在发病机制或感染严重程度上对男性和女性的影响不同。然而,之前的一项研究报道了鼻内鼠疫耶尔森氏菌攻击后性别偏见疫苗的有效性。作为开发安全有效疫苗的一部分，潜在性别差异的特征至关重要。
■在这项研究中，我们使用异源初免方法评估了雄性和雌性BALB/c小鼠的新型疫苗，并监测了存活率。器官中的细菌负荷，和免疫学相关因素。我们的疫苗策略包括两次皮下免疫,随后用雾化毒力未包封的鼠疫耶尔森氏菌进行攻击。用活鼠疫菌pgm-pPst-Δcaf1，活鼠疫菌pgm-pPst-Δcaf1/ΔyopD的组合免疫小鼠，或与佐剂组合的重组F1-V(rF1-V)。
■最有效的疫苗方案是最初用rF1-V引发，然后用任一减毒活菌株加强。然而,这种策略和其他策略在雌性小鼠中更具保护性。雄性具有较高的细菌负荷和不同的细胞因子表达模式和血清抗体滴度。如在雌性小鼠中反复观察到的,雄性小鼠没有表现出疫苗接种和抗生素治疗之间的协同作用。
■这项研究提供了有关异源疫苗策略的新知识，鼠疫疫苗效力的性别差异，以及雄性和雌性小鼠之间不同的免疫因素。
■在这项研究中，我们使用异源初免方法评估了雄性和雌性BALB/c小鼠的新型疫苗，并监测了存活率。器官中的细菌负荷，和免疫学相关因素。我们的疫苗策略包括两次皮下免疫,随后用雾化毒力未包封的鼠疫耶尔森氏菌进行攻击。用活鼠疫菌pgm-pPst-Δcaf1，活鼠疫菌pgm-pPst-Δcaf1/ΔyopD的组合免疫小鼠，或与佐剂组合的重组F1-V(rF1-V)。
■最有效的疫苗方案是最初用rF1-V引发，然后用任一减毒活菌株加强。然而,这种策略和其他策略在雌性小鼠中更具保护性。雄性具有较高的细菌负荷和不同的细胞因子表达模式和血清抗体滴度。如在雌性小鼠中反复观察到的,雄性小鼠没有表现出疫苗接种和抗生素治疗之间的协同作用。
■这项研究提供了有关异源疫苗策略的新知识，鼠疫疫苗效力的性别差异，以及雄性和雌性小鼠之间不同的免疫因素。
