Thammavongsa Vilasack, Rauch Sabine, Kim Hwan Keun, Missiakas Dominique M, Schneewind Olaf
Department of Microbiology, University of Chicago, 920 East 58th Street, Chicago, IL 60637, USA.
Department of Microbiology, University of Chicago, 920 East 58th Street, Chicago, IL 60637, USA.
Vaccine. 2015 Jan 15;33(4):523-6. doi: 10.1016/j.vaccine.2014.11.051. Epub 2014 Dec 6.
Staphylococcus aureus is a cause of sepsis and meningitis in very-low-birth-weight (VLBW) infants. Clinical trials with S. aureus specific antibodies failed to protect VLBW neonates, which may be due to the immune evasive attributes of staphylococcal protein A (SpA). Here we show that mouse monoclonal antibody SpAKKAA-mAb 3F6, which neutralizes the immunoglobulin Fcγ-binding and B cell receptor crosslinking attributes of SpA, protects neonatal mice against S. aureus sepsis and raises protective immunity against subsequent staphylococcal infection. We developed a humanized SpAKKAA-mAb that protects neonatal mice against S. aureus sepsis and may therefore be subjected to clinical testing in VLBW neonates.
金黄色葡萄球菌是极低出生体重（VLBW）婴儿败血症和脑膜炎的病因。针对金黄色葡萄球菌特异性抗体的临床试验未能保护VLBW新生儿，这可能归因于葡萄球菌蛋白A（SpA）的免疫逃避特性。在此我们表明，小鼠单克隆抗体SpAKKAA-mAb 3F6可中和SpA的免疫球蛋白Fcγ结合和B细胞受体交联特性，能保护新生小鼠免受金黄色葡萄球菌败血症感染，并增强对后续葡萄球菌感染的保护性免疫。我们研发了一种人源化SpAKKAA-mAb，它能保护新生小鼠免受金黄色葡萄球菌败血症感染，因此可能会在VLBW新生儿中进行临床试验。
