4.6 Article

Immunoprofiles associated with controlled human malaria infection and naturally acquired immunity identify a shared IgA pre-erythrocytic immunoproteome

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NPJ VACCINES
卷 6, 期 1, 页码 -

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NATURE PORTFOLIO
DOI: 10.1038/s41541-021-00363-y

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资金

  1. National Institute of Allergy and Infectious Diseases (NIAID)/National Institutes of Health (NIH) [U19AI065683]
  2. Fogarty International Center of the NIH [D43TW001589]
  3. Doris Duke Charitable Foundation
  4. Howard Hughes Medical Institute
  5. University of Maryland, Baltimore, Institute for Clinical & Translational Research (ICTR)
  6. National Center for Advancing Translational Sciences (NCATS) Clinical Translational Science Award (CTSA) [1UL1TR003098]
  7. NIAID [N01-AI25461, HHSN272200800057C, R44AI055229, R44AI058375, HSN272201300022I, HHSN272201500002C, 2R44AI058375-06A1, K23AI125720]
  8. Sanaria, Inc. [W81XWH-JW14843]
  9. University of Maryland School of Medicine Passano Foundation Clinician-Investigator Award
  10. NIH [U19 AI110820, U01 AI089342, R01 AE141900, U01AI110852, AI-067954, R01AI095916, U19AI089686]
  11. Geneva Foundation [V-12VAXHFRS-03]
  12. Medical Technology Enterprise Consortium [MTEC-17-01]
  13. Pfizer [C4591001]
  14. Joint Warfighter Medical Research Program [W81XWH-JW14843]
  15. National Heart, Lung, and Blood Institute [K01HL140285-01A1]

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This study assessed IgG and IgA antibody responses in adult sera collected during CHMI studies and in Malian children, and identified differences in the immunoproteome among naive individuals and exposed individuals. It also expanded the list of pre-erythrocytic antigens recognized by the immune system and highlighted the potential of IgA responses as vaccine candidates.
Knowledge of the Plasmodium falciparum antigens that comprise the human liver stage immunoproteome is important for pre-erythrocytic vaccine development, but, compared with the erythrocytic stage immunoproteome, more challenging to classify. Previous studies of P. falciparum antibody responses report IgG and rarely IgA responses. We assessed IgG and IgA antibody responses in adult sera collected during two controlled human malaria infection (CHMI) studies in malaria-naive volunteers and in 1- to 6-year-old malaria-exposed Malian children on a 251 P. falciparum antigen protein microarray. IgG profiles in the two CHMI groups were equivalent and differed from Malian children. IgA profiles were robust in the CHMI groups and a subset of Malian children. We describe immunoproteome differences in naive vs. exposed individuals and report pre-erythrocytic proteins recognized by the immune system. IgA responses detected in this study expand the list of pre-erythrocytic antigens for further characterization as potential vaccine candidates.

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