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TitleMultifunctional antibody responses from a primate outbreak inform vaccine design.
Journal, issue, pagesSci Transl Med, Vol. 18, Issue 865, Page eaef7084, Year 2026
Publish dateSep 2, 2026
AuthorsRobert M Gallant / Paul Savarino / Sophia Pulido / Morgan S A Gilman / Ti Lu / Jennifer Hayes / Nicholas L Xerri / Torrey Williams / Mark A Ochoa / Zackary Dietz / Eric Peterson / Timothy Scott / Faye Hartmann / Stephen G Baker / Robert W Kaminski / Devin Sok / Andrew C Kruse / Wendy Picking / Saverio V Capuano / Hayden R Schmidt /
PubMed AbstractThere is currently no approved vaccine for spp., a leading cause of diarrhea with increasing rates of antimicrobial resistance. vaccine development is complicated in part by an incomplete ...There is currently no approved vaccine for spp., a leading cause of diarrhea with increasing rates of antimicrobial resistance. vaccine development is complicated in part by an incomplete understanding of the structural and molecular determinants of immunity. To address this, we isolated monoclonal antibodies against candidate vaccine antigens using samples from a outbreak in a nonhuman primate (NHP) research facility. We found that antibodies targeting the O-antigen can undergo substantial affinity maturation (>10%) to acquire broad cross-reactivity across serotypes. We also found that the virulence-associated type III secretion system (T3SS) proteins IpaD and IpaB elicit moderate T cell and robust antibody responses. T3SS antibodies could either inhibit or enhance bacterial virulence in vitro and differed in vivo depending on their epitope specificity. Collectively, these findings provide insights into protective and deleterious immune responses against that directly inform vaccine immunogen design.
External linksSci Transl Med / PubMed:42685149
MethodsEM (single particle)
Resolution3.3 - 3.4 Å
Structure data

74629

9zrs

EMDB-74629, PDB-9zrs:
Shigella flexneri type III secretion system (T3SS) protein IpaD bound to hemolysis blocking Fab D02-F2 and hemolysis enhancing Fab D02-E4
Method: EM (single particle) / Resolution: 3.4 Å

74630

9zrt

EMDB-74630, PDB-9zrt:
Shigella flexneri type III secretion system (T3SS) protein IpaD bound to hemolysis blocking antibody fragment D13r-34
Method: EM (single particle) / Resolution: 3.3 Å

Source
  • shigella flexneri (bacteria)
  • macaca mulatta (Rhesus monkey)
KeywordsPROTEIN TRANSPORT / T3SS / epitope / vaccine antigen / SipD homolog

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