Targeted lipid A modification of Shigella vaccine strains reduced endotoxicity without compromising immunogenicity or invasiveness
Sherman, M. E.; Michalski, J.; Das, S.; Yang, H.; Barnoy, S.; Chandrasekaran, L.; Venkatesan, M.; Ernst, R. K.
Show abstract
Shigella infection contributes significantly to the global disease burden, especially affecting young children in developing countries. Currently, a vaccine against Shigella is unavailable and the prevalence of antibiotic resistance amongst Shigella species is continually rising. Live-attenuated Shigella vaccine candidates developed at Walter Reed Army Institute of Research have shown remarkable immunogenicity but exhibit adverse reactogenicity, most likely due to the highly toxic lipid A moiety present on the bacterial membrane. Previous attempts at reducing the endotoxicity have focused on deletion of intrinsic lipid A biosynthesis enzymes. In this study, we instead introduce exogenous lipid A modifying enzymes, generating targeted modifications in the lipid A structure, leading to a dampened TLR4 response within the host. In doing so, we generated vaccine candidates with detoxified lipid A and unaltered O-antigen structure thereby preserving the serotype-specific immunity while reducing endotoxicity.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Surface-modified measles vaccines encoding oligomeric, fusion-stabilized SARS-CoV-2 spike glycoproteins bypass measles seropositivity, boosting neutralizing antibody responses to omicron and historical variants. 93%
- Staphylococcal DNA repair is required for infection 93%
- Tetravalent SARS-CoV-2 S1 Subunit Protein Vaccination Elicits Robust Humoral and Cellular Immune Responses in SIV-Infected Rhesus Macaque Controllers 92%
Similar papers in this journal
- Capsular polysaccharide inhibits vaccine-induced O-antigen antibody binding and function across both classical and hypervirulent K2:O1 strains of Klebsiella pneumoniae 94%
- Single domain antibodies against enteric pathogen virulence factors are active as curli fiber fusions on probiotic E. coli Nissle 1917 93%
- Comparative virulence analysis of seven diverse strains of Orientia tsutsugamushi reveals a multifaceted and complex interplay of virulence factors responsible for disease. 93%
Similar papers in this journal
Similar papers in this journal
- Immunization of mice with chimeric antigens displaying selected epitopes confers protection against intestinal colonization and renal damage caused by Shiga toxin-producing Escherichia coli (STEC). 94%
- Virus-like particle vaccines targeting a key epitope in circumsporozoite protein provide sterilizing immunity against malaria 94%
- A self-amplifying RNA vaccine against COVID-19 with long-term room-temperature stability 94%
Similar papers in this journal
- Assessment of chemical methods in the extraction of spore surface layers in Clostridioides difficile spores 91%
- Clostridioides difficile-mucus interactions encompass shifts in gene expression, metabolism, and biofilm formation 91%
- Durable Immunity to Ricin Toxin Elicited by a Thermostable, Lyophilized Subunit Vaccine 91%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.