Vi-specific serological correlates of protection for typhoid fever
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Vi-specific serological correlates of protection for typhoid fever. / Jin, Celina; Hill, Jennifer; Gunn, Bronwyn M.; Yu, Wen Han; Dahora, Lindsay C.; Jones, Elizabeth; Johnson, Mari; Gibani, Malick M.; Spreng, Rachel L.; Alam, S. Munir; Nebykova, Anna; Juel, Helene B.; Dennison, S. Moses; Seaton, Kelly E.; Fallon, Jonathan K.; Tomaras, Georgia D.; Alter, Galit; Pollard, Andrew J.
In: The Journal of Experimental Medicine, Vol. 218, No. 2, e20201116, 2020.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Vi-specific serological correlates of protection for typhoid fever
AU - Jin, Celina
AU - Hill, Jennifer
AU - Gunn, Bronwyn M.
AU - Yu, Wen Han
AU - Dahora, Lindsay C.
AU - Jones, Elizabeth
AU - Johnson, Mari
AU - Gibani, Malick M.
AU - Spreng, Rachel L.
AU - Alam, S. Munir
AU - Nebykova, Anna
AU - Juel, Helene B.
AU - Dennison, S. Moses
AU - Seaton, Kelly E.
AU - Fallon, Jonathan K.
AU - Tomaras, Georgia D.
AU - Alter, Galit
AU - Pollard, Andrew J.
PY - 2020
Y1 - 2020
N2 - Typhoid Vi vaccines have been shown to be efficacious in children living in endemic regions; however, a widely accepted correlate of protection remains to be established. We applied a systems serology approach to identify Vi-specific serological correlates of protection using samples obtained from participants enrolled in an experimental controlled human infection study. Participants were vaccinated with Vi-tetanus toxoid conjugate (Vi-TT) or unconjugated Vi-polysaccharide (Vi-PS) vaccines and were subsequently challenged with Salmonella Typhi bacteria. Multivariate analyses identified distinct protective signatures for Vi-TT and Vi-PS vaccines in addition to shared features that predicted protection across both groups. Vi IgA quantity and avidity correlated with protection from S. Typhi infection, whereas higher fold increases in Vi IgG responses were associated with reduced disease severity. Targeted antibody-mediated functional responses, particularly neutrophil phagocytosis, were also identified as important components of the protective signature. These humoral markers could be used to evaluate and develop efficacious Vi-conjugate vaccines and assist with accelerating vaccine availability to typhoid-endemic regions.
AB - Typhoid Vi vaccines have been shown to be efficacious in children living in endemic regions; however, a widely accepted correlate of protection remains to be established. We applied a systems serology approach to identify Vi-specific serological correlates of protection using samples obtained from participants enrolled in an experimental controlled human infection study. Participants were vaccinated with Vi-tetanus toxoid conjugate (Vi-TT) or unconjugated Vi-polysaccharide (Vi-PS) vaccines and were subsequently challenged with Salmonella Typhi bacteria. Multivariate analyses identified distinct protective signatures for Vi-TT and Vi-PS vaccines in addition to shared features that predicted protection across both groups. Vi IgA quantity and avidity correlated with protection from S. Typhi infection, whereas higher fold increases in Vi IgG responses were associated with reduced disease severity. Targeted antibody-mediated functional responses, particularly neutrophil phagocytosis, were also identified as important components of the protective signature. These humoral markers could be used to evaluate and develop efficacious Vi-conjugate vaccines and assist with accelerating vaccine availability to typhoid-endemic regions.
U2 - 10.1084/jem.20201116
DO - 10.1084/jem.20201116
M3 - Journal article
C2 - 33180929
AN - SCOPUS:85096082312
VL - 218
JO - The Journal of Experimental Medicine
JF - The Journal of Experimental Medicine
SN - 0022-1007
IS - 2
M1 - e20201116
ER -
ID: 253781433