Phase variable acetylation of lipooligosaccharide modifies antibody production and opsonophagocytic killing of non-typeable Haemophilus influenzae. iScience 2023 Oct 20;26(10):107785
Date
09/20/2023Pubmed ID
37727736Pubmed Central ID
PMC10505976DOI
10.1016/j.isci.2023.107785Scopus ID
2-s2.0-85170435505 (requires institutional sign-in at Scopus site)Abstract
Non-typeable Haemophilus influenzae (NTHi) causes millions of infections each year. Though it is primarily known to cause otitis media, recent studies have shown NTHi is emerging as a primary pathogen for invasive infection, prompting the need for new vaccines and treatments. Lipooligosaccharide (LOS) has been identified as a potential vaccine candidate due to its immunogenic nature and outer membrane localization. Yet, phase variable expression of genes involved in LOS synthesis has complicated vaccine development. In this study, we used a chinchilla model of otitis media to investigate how phase variation of oafA, a gene involved in LOS biosynthesis, affects antibody production in response to infection. We found that acetylation of LOS by OafA inhibited production of LOS-specific antibodies during infection and that NTHi expressing acetylated LOS were subsequently better protected against opsonophagocytic killing. These findings highlight the importance of understanding how phase variable modifications might affect vaccine efficacy and success.
