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Working correlates of protection predict SchuS4-derived-vaccine candidates with improved efficacy against an intracellular bacterium, Francisella tularensis.
De Pascalis, Roberto; Frey, Blake; Rice, Helen M; Bhargava, Varunika; Wu, Terry H; Peterson, Ross L; Conlan, J Wayne; Sjöstedt, Anders; Elkins, Karen L.
Afiliação
  • De Pascalis R; Laboratory of Mucosal Pathogens and Cellular Immunology, Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA. roberto.depascalis@fda.hhs.gov.
  • Frey B; Laboratory of Mucosal Pathogens and Cellular Immunology, Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.
  • Rice HM; University of Alabama-Birmingham, Birmingham, AL, USA.
  • Bhargava V; Laboratory of Mucosal Pathogens and Cellular Immunology, Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.
  • Wu TH; University of Bristol, Bristol, UK.
  • Peterson RL; Laboratory of Mucosal Pathogens and Cellular Immunology, Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.
  • Conlan JW; Regeneron Pharmaceuticals, Tarrytown, NY, USA.
  • Sjöstedt A; Center for Infectious Disease and Immunity and Department of Internal Medicine, University of New Mexico, Albuquerque, NM, USA.
  • Elkins KL; Vaccine Evaluation Branch, Division of Biostatistics, Office of Biostatistics and Epidemiology, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.
NPJ Vaccines ; 7(1): 95, 2022 Aug 17.
Article em En | MEDLINE | ID: mdl-35977964
ABSTRACT
Francisella tularensis, the causative agent of tularemia, is classified as Tier 1 Select Agent with bioterrorism potential. The efficacy of the only available vaccine, LVS, is uncertain and it is not licensed in the U.S. Previously, by using an approach generally applicable to intracellular pathogens, we identified working correlates that predict successful vaccination in rodents. Here, we applied these correlates to evaluate a panel of SchuS4-derived live attenuated vaccines, namely SchuS4-ΔclpB, ΔclpB-ΔfupA, ΔclpB-ΔcapB, and ΔclpB-ΔwbtC. We combined in vitro co-cultures to quantify rodent T-cell functions and multivariate regression analyses to predict relative vaccine strength. The predictions were tested by rat vaccination and challenge studies, which demonstrated a clear relationship between the hierarchy of in vitro measurements and in vivo vaccine protection. Thus, these studies demonstrated the potential power a panel of correlates to screen and predict the efficacy of Francisella vaccine candidates, and in vivo studies in Fischer 344 rats confirmed that SchuS4-ΔclpB and ΔclpB-ΔcapB may be better vaccine candidates than LVS.

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies / Risk_factors_studies Idioma: En Revista: NPJ Vaccines Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies / Risk_factors_studies Idioma: En Revista: NPJ Vaccines Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos