Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, Oxford, UK.
Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, Oxford, UK.
Vaccine. 2023 May 5;41(19):3047-3057. doi: 10.1016/j.vaccine.2023.04.012. Epub 2023 Apr 8.
Q fever is a highly infectious zoonosis caused by the Gram-negative bacterium Coxiella burnetii. The worldwide distribution of Q fever suggests a need for vaccines that are more efficacious, affordable, and does not induce severe adverse reactions in vaccine recipients with pre-existing immunity against Q fever. Potential Q fever vaccine antigens include lipopolysaccharide (LPS) and several C. burnetii surface proteins. Antibodies elicited by purified C. burnetii lipopolysaccharide (LPS) correlate with protection against Q fever, while antigens encoded by adenoviral vectored vaccines can induce cellular immune responses which aid clearing of intracellular pathogens. In the present study, the immunogenicity and the protection induced by adenoviral vectored constructs formulated with the addition of LPS were assessed. Multiple vaccine constructs encoding single or fusion antigens from C. burnetii were synthesised. The adenoviral vectored vaccine constructs alone elicited strong cellular immunity, but this response was not correlative with protection in mice. However, vaccination with LPS was significantly associated with lower weight loss post-bacterial challenge independent of co-administration with adenoviral vaccine constructs, supporting further vaccine development based on LPS.
Q 热是由革兰氏阴性细菌贝氏柯克斯体引起的高度传染性动物传染病。Q 热的全球分布表明需要更有效、更实惠的疫苗,并且不会在对 Q 热有预先免疫的疫苗接种者中引起严重不良反应。潜在的 Q 热疫苗抗原包括脂多糖(LPS)和几种贝氏柯克斯体表面蛋白。由纯化的贝氏柯克斯体脂多糖(LPS)引发的抗体与预防 Q 热相关,而腺病毒载体疫苗编码的抗原可以诱导细胞免疫反应,有助于清除细胞内病原体。在本研究中,评估了添加 LPS 的腺病毒载体构建体诱导的免疫原性和保护作用。合成了编码来自贝氏柯克斯体的单一或融合抗原的多种腺病毒载体疫苗构建体。单独的腺病毒载体疫苗构建体可引发强烈的细胞免疫反应,但这种反应与小鼠的保护无关。然而,与腺病毒疫苗构建体共同给药无关,用 LPS 进行疫苗接种与细菌攻击后体重减轻显著相关,支持基于 LPS 的进一步疫苗开发。