Moustafa Dina A, DiGiandomenico Antonio, Raghuram Vishnu, Schulman Marc, Scarff Jennifer M, Davis Michael R, Varga John J, Dean Charles R, Goldberg Joanna B
Department of Pediatrics, Division of Pulmonary, Asthma, Cystic Fibrosis, and Sleep, Emory University School of Medicine, Atlanta, Georgia, USA.
Emory+Children's Center for Cystic Fibrosis and Airway Disease Research, Emory University School of Medicine, Atlanta, Georgia, USA.
bioRxiv. 2023 Jul 13:2023.07.13.548830. doi: 10.1101/2023.07.13.548830.
There are currently no approved vaccines against the opportunistic pathogen . Among vaccine targets, the lipopolysaccharide (LPS) O antigen of is the most immunodominant protective candidate. There are twenty different O antigens composed of different repeat sugars structures conferring serogroup specificity, and ten are found most frequently in infection. Thus, one approach to combat infection by could be to generate immunity with a vaccine cocktail that includes all these serogroups. Serogroup O9 is one of the ten serogroups commonly found in infection, but it has never been developed into a vaccine, likely due, in part, to the acid labile nature of the O9 polysaccharide. Our laboratory has previously shown that intranasal administration of an attenuated strain expressing the serogroup O11 LPS O antigen was effective in clearing and preventing mortality in mice following intranasal challenge with serogroup O11 . Consequently, we set out to develop a . serogroup O9 vaccine using a similar approach. Here we show that expressing serogroup O9 triggered an antibody-mediated immune response following intranasal administration to mice and that it conferred protection from serogroup O9 in a murine model of acute pneumonia.
目前尚无针对这种机会性病原菌的获批疫苗。在疫苗靶点中,该菌的脂多糖(LPS)O抗原是最具免疫优势的保护性候选抗原。有20种不同的O抗原,由不同的重复糖结构组成,赋予血清群特异性,其中10种在感染中最常出现。因此,对抗该菌感染的一种方法可能是用包含所有这些血清群的疫苗混合物产生免疫力。血清群O9是感染中常见的10种血清群之一,但它从未被开发成疫苗,部分原因可能是O9多糖的酸不稳定性质。我们实验室先前已表明,鼻内给予表达该菌血清群O11 LPS O抗原的减毒株,在小鼠经鼻内感染血清群O11后,对清除感染和预防死亡有效。因此,我们着手采用类似方法开发一种该菌血清群O9疫苗。在此我们表明,表达血清群O9的该菌经鼻内给予小鼠后引发了抗体介导的免疫反应,并且在急性肺炎小鼠模型中它对血清群O9感染具有保护作用。