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Non-protective immune imprint underlies failure of Staphylococcus aureus IsdB vaccine.
Tsai, Chih-Ming; Caldera, J R; Hajam, Irshad A; Chiang, Austin W T; Tsai, Chih-Hsiung; Li, Haining; Díez, María Lázaro; Gonzalez, Cesia; Trieu, Desmond; Martins, Gislâine A; Underhill, David M; Arditi, Moshe; Lewis, Nathan E; Liu, George Y.
Afiliación
  • Tsai CM; Department of Pediatrics, University of California, San Diego, San Diego, CA 92093, USA.
  • Caldera JR; Department of Pediatrics, University of California, San Diego, San Diego, CA 92093, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Hajam IA; Department of Pediatrics, University of California, San Diego, San Diego, CA 92093, USA.
  • Chiang AWT; Department of Pediatrics, University of California, San Diego, San Diego, CA 92093, USA.
  • Tsai CH; Department of Life Sciences, National Cheng Kung University, Tainan 701, Taiwan.
  • Li H; Department of Bioengineering, University of California, San Diego, San Diego, CA 92093, USA.
  • Díez ML; Department of Pediatrics, University of California, San Diego, San Diego, CA 92093, USA.
  • Gonzalez C; Department of Pediatrics, University of California, San Diego, San Diego, CA 92093, USA.
  • Trieu D; Department of Pediatrics, University of California, San Diego, San Diego, CA 92093, USA.
  • Martins GA; Research Division of Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Medicine, Cedars-Sinai Me
  • Underhill DM; Research Division of Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Medicine, Cedars-Sinai Me
  • Arditi M; Division of Pediatric Infectious Diseases, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Lewis NE; Department of Pediatrics, University of California, San Diego, San Diego, CA 92093, USA; Department of Bioengineering, University of California, San Diego, San Diego, CA 92093, USA.
  • Liu GY; Department of Pediatrics, University of California, San Diego, San Diego, CA 92093, USA; Division of Infectious Diseases, Rady Children's Hospital, San Diego, CA 92123, USA. Electronic address: gyliu@ucsd.edu.
Cell Host Microbe ; 30(8): 1163-1172.e6, 2022 08 10.
Article en En | MEDLINE | ID: mdl-35803276
Humans frequently encounter Staphylococcus aureus (SA) throughout life. Animal studies have yielded SA candidate vaccines, yet all human SA vaccine trials have failed. One notable vaccine "failure" targeted IsdB, critical for host iron acquisition. We explored a fundamental difference between humans and laboratory animals-natural SA exposure. Recapitulating the failed phase III IsdB vaccine trial, mice previously infected with SA do not mount protective antibody responses to vaccination, unlike naive animals. Non-protective antibodies exhibit increased α2,3 sialylation that blunts opsonophagocytosis and preferentially targets a non-protective IsdB domain. IsdB vaccination of SA-infected mice recalls non-neutralizing humoral responses, further reducing vaccine efficacy through direct antibody competition. IsdB vaccine interference was overcome by immunization against the IsdB heme-binding domain. Purified human IsdB-specific antibodies also blunt IsdB passive immunization, and additional SA vaccines are susceptible to SA pre-exposure. Thus, failed anti-SA immunization trials could be explained by non-protective imprint from prior host-SA interaction.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones Estafilocócicas / Vacunas / Proteínas de Transporte de Catión Límite: Animals / Humans Idioma: En Revista: Cell Host Microbe Asunto de la revista: MICROBIOLOGIA Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones Estafilocócicas / Vacunas / Proteínas de Transporte de Catión Límite: Animals / Humans Idioma: En Revista: Cell Host Microbe Asunto de la revista: MICROBIOLOGIA Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos