Vaccine Research & Development Center, Department of Physiology & Biophysics, University of California, Irvine, Irvine, CA, United States.
Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, Bryan, TX, United States.
Front Immunol. 2023 Jul 18;14:1192821. doi: 10.3389/fimmu.2023.1192821. eCollection 2023.
Vaccines are among the most cost-effective public health measures for controlling infectious diseases. is the etiological agent of Q fever, a disease with a wide clinical spectrum that ranges from mild symptoms, such as fever and fatigue, to more severe disease, such as pneumonia and endocarditis. The formalin-inactivated whole-cell vaccine Q-VAX contains hundreds of antigens and confers lifelong protection in humans, but prior sensitization from infection or vaccination can result in deleterious reactogenic responses to vaccination. Consequently, there is great interest in developing non-reactogenic alternatives based on adjuvanted recombinant proteins. In this study, we aimed to develop a multivalent vaccine that conferred protection with reduced reactogenicity. We hypothesized that a multivalent vaccine consisting of multiple antigens would be more immunogenic and protective than a monovalent vaccine owing to the large number of potential protective antigens in the proteome. To address this, we identified immunogenic T and B cell antigens, and selected proteins were purified to evaluate with a combination adjuvant (IVAX-1), with or without lipopolysaccharide (LPS) in immunogenicity studies in mice and in a Hartley guinea pig intratracheal aerosol challenge model using strain NMI RSA 493. The data showed that multivalent vaccines are more immunogenic than monovalent vaccines and more closely emulate the protection achieved by Q-VAX. Although six antigens were the most immunogenic, we also discovered that multiplexing beyond four antigens introduces detectable reactogenicity, indicating that there is an upper limit to the number of antigens that can be safely included in a multivalent Q-fever vaccine. LPS also demonstrates efficacy as a vaccine antigen in conferring protection in an otherwise monovalent vaccine formulation, suggesting that its addition in multivalent vaccines, as demonstrated by a quadrivalent formulation, would improve protective responses.
疫苗是控制传染病最具成本效益的公共卫生措施之一。是 Q 热的病原体，该病具有广泛的临床谱，从轻度症状（如发热和疲劳）到更严重的疾病（如肺炎和心内膜炎）不等。福尔马林灭活全细胞疫苗 Q-VAX 含有数百种抗原，可在人类中提供终身保护，但先前的感染或疫苗接种致敏会导致疫苗接种产生有害的反应原性反应。因此，人们非常有兴趣根据佐剂重组蛋白开发非反应原性替代品。在这项研究中，我们旨在开发一种具有降低反应原性的多价疫苗。我们假设，由于 蛋白组中有大量潜在的保护性抗原，由多种抗原组成的多价疫苗将比单价疫苗更具免疫原性和保护性。为了解决这个问题，我们确定了免疫原性 T 和 B 细胞抗原，并选择了蛋白质进行纯化，以评估组合佐剂（IVAX-1）与或不与 脂多糖（LPS）在免疫原性研究中的作用 在小鼠和哈特利豚鼠气管内气溶胶挑战模型中使用 菌株 NMI RSA 493。数据表明，多价疫苗比单价疫苗更具免疫原性，更能模拟 Q-VAX 实现的保护。尽管有六种抗原最具免疫原性，但我们还发现，在四价以上的疫苗中添加抗原会引起可检测的反应原性，这表明在多价 Q 热疫苗中可以安全包含的抗原数量存在上限。 LPS 还作为疫苗抗原发挥作用，在单价疫苗配方中提供保护，表明在四价配方中添加 LPS 会改善保护性反应。
