Immune Response Characterization After Controlled Infection with Lyophilized Shigella sonnei 53G

Details

• Personal Author:
  Bourgeois AL ; Chandrasekaran L ; Clarkson KA ; Detizio K ; Dickey M ; Frenck RW Jr. ; Heaney CD ; Hoeper A ; Kaminski RW ; McNeal M ; Parker S ; Porter CK ; Suvarnapunya AE ; Venkatesan MM ; Weerts HP
• Description:
  Shigella is a major cause of moderate to severe diarrhea largely affecting children (<5 years old) living in low- and middle-income countries. Several vaccine candidates are in development, and controlled human infection models (CHIMs) can be useful tools to provide an early assessment of vaccine efficacy and potentially support licensure. A lyophilized strain of S. sonnei 53G was manufactured and evaluated to establish a dose that safely and reproducibly induced a >/=60% attack rate. Samples were collected pre- and postchallenge to assess intestinal inflammatory responses, antigen-specific serum and mucosal antibody responses, functional antibody responses, and memory B cell responses. Infection with S. sonnei 53G induced a robust intestinal inflammatory response as well as antigen-specific antibodies in serum and mucosal secretions and antigen-specific IgA- and IgG-secreting B cells positive for the a4B7 gut-homing marker. There was no association between clinical disease outcomes and systemic or functional antibody responses postchallenge; however, higher lipopolysaccharide (LPS)-specific serum IgA- and IgA-secreting memory B cell responses were associated with a reduced risk of disease postchallenge. This study provides unique insights into the immune responses pre- and postinfection with S. sonnei 53G in a CHIM, which could help guide the rational design of future vaccines to induce protective immune responses more analogous to those triggered by infection. IMPORTANCE: Correlate(s) of immunity have yet to be defined for shigellosis. As previous disease protects against subsequent infection in a serotype-specific manner, investigating immune response profiles pre- and postinfection provides an opportunity to identify immune markers potentially associated with the development of protective immunity and/or with a reduced risk of developing shigellosis postchallenge. This study is the first to report such an extensive characterization of the immune response after challenge with S. sonnei 53G. Results demonstrate an association of progression to shigellosis with robust intestinal inflammatory and mucosal gut-homing responses. An important finding in this study was the association of elevated Shigella LPS-specific serum IgA and memory B cell IgA responses at baseline with reduced risk of disease. The increased baseline IgA responses may contribute to the lack of dose response observed in the study and suggests that IgA responses should be further investigated as potential correlates of immunity. [Description provided by NIOSH]
• Subjects:
  Antibodies Immune System Occupational Health Safety
• Keywords:
  Antibody Antibody Response Author Keywords: Shigella Bacteria Bacterial Infections Controlled Human Infection Model Gut-homing Responses Gut Homing Immune Reaction Immune System Immunogenicity Immunological Memory Infectious Agents Shigella Sonnei

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• ISSN:
  2379-5042
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  District of Columbia ; Maryland ; Ohio ; OSHA Region 3 ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  5
• Issue:
  5
• NIOSHTIC Number:
  nn:20061417
• Citation:
  mSphere 2020 Sep-Oct; 5(5):e00988-19
• Contact Point Address:
  Robert W. Kaminski, Department of Enteric Infections, Bacterial Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA
• Email:
  Robert.W.Kaminski.civ@mail.mil
• Federal Fiscal Year:
  2020
• Performing Organization:
  Johns Hopkins University, Baltimore, Maryland
• Peer Reviewed:
  True
• Start Date:
  20120701
• Source Full Name:
  mSphere
• End Date:
  20150630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:70daaaa9f2637d6d77c03d7355f8a579e81b5754cc2a6226f8b88ffcd93d6a3b6d0c6248e1d82ce5a5383a3ddaaff9b912cc6c6d71065ad9dc366aef5ba27c92
• Download URL:
  https://stacks.cdc.gov/view/cdc/224953/cdc_224953_DS1.pdf
• File Type:
  [PDF - 379.86 KB ]