Persistence of antibody after a vi-tetanus toxoid conjugate vaccine and effect of boosting with a plain polysaccharide vaccine on Vi antibody and antigen-specific B cells

<strong>Background:</strong> Salmonella enterica serovar Typhi is estimated to cause 9 to 13 million cases of typhoid fever annually. Typhoid conjugate vaccines represent a promising prophylactic measure to prevent disease, but there are few data assessing persistence of immunity. The ef...

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Main Authors: Bentley, T, Jones, E, Jin, C, Moore, M, Gardner, J, Hill, J, Pollard, AJ
Format: Journal article
Language:English
Published: Frontiers Media 2021
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author Bentley, T
Jones, E
Jin, C
Moore, M
Gardner, J
Hill, J
Pollard, AJ
author_facet Bentley, T
Jones, E
Jin, C
Moore, M
Gardner, J
Hill, J
Pollard, AJ
author_sort Bentley, T
collection OXFORD
description <strong>Background:</strong> Salmonella enterica serovar Typhi is estimated to cause 9 to 13 million cases of typhoid fever annually. Typhoid conjugate vaccines represent a promising prophylactic measure to prevent disease, but there are few data assessing persistence of immunity. The effect of a Vi polysaccharide booster vaccine in individuals previously vaccinated with the Vi-tetanus toxoid typhoid conjugate vaccine has not been assessed previously. <br><strong> Methods: </strong>Thirty five healthy adult volunteers received a single dose of the Vi conjugate vaccine (Vi-TT) and 37 received a single dose of Vi polysaccharide vaccine (Vi-PS) prior to oral challenge with live S. Typhi bacteria as part of a randomised controlled, phase 2b study. In addition to data previously published showing persistence of Vi IgG and IgA antibodies for 7 months after Vi vaccination, titres were measured at intervals until 13 months post-vaccination. Ten participants who received Vi-TT (both challenged and unchallenged) were re-vaccinated with Vi-PS at an interval of 19-23 months post-prime. Anti-Vi IgG and IgA titres, and Vi-specific antibody secreting cells and memory B cells were measured at seven days and one month post-boost. <br><strong> Findings: </strong>Vi IgG and IgA antibody titres remained significantly elevated above baseline levels 13 months after priming with Vi-TT, with a 4-fold rise retained in 90% and 88% of recipients (Vi IgG and IgA, respectively). Anti-Vi IgG and IgA antibody titres were found to persist at higher levels in participants who received a single dose of Vi-TT than in those who received Vi-PS. No significant boost in Vi-antibody titre was observed in response to oral challenge with S. Typhi bacteria, one month after vaccination. Following a Vi-PS booster vaccination in those previously vaccinated with Vi-TT, anti-Vi IgG and IgA titres were significantly elevated, with similar titres observed at one month post-boost compared with one month after primary vaccination. The frequency of Vi-specific IgA antibody secreting cells increased significantly 7 days post-boost compared with pre-boost. No memory B cell response was observed following Vi-PS booster vaccination. <br><strong> Interpretation: </strong>Strong persistence of anti-Vi IgG and IgA following Vi-TT vaccination suggests that the conjugate vaccine may offer durable protection, supporting its use in endemic settings.
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spelling oxford-uuid:9a98b283-194b-425c-bea6-51b5243614472023-09-21T13:48:58ZPersistence of antibody after a vi-tetanus toxoid conjugate vaccine and effect of boosting with a plain polysaccharide vaccine on Vi antibody and antigen-specific B cellsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:9a98b283-194b-425c-bea6-51b524361447EnglishSymplectic ElementsFrontiers Media2021Bentley, TJones, EJin, CMoore, MGardner, JHill, JPollard, AJ<strong>Background:</strong> Salmonella enterica serovar Typhi is estimated to cause 9 to 13 million cases of typhoid fever annually. Typhoid conjugate vaccines represent a promising prophylactic measure to prevent disease, but there are few data assessing persistence of immunity. The effect of a Vi polysaccharide booster vaccine in individuals previously vaccinated with the Vi-tetanus toxoid typhoid conjugate vaccine has not been assessed previously. <br><strong> Methods: </strong>Thirty five healthy adult volunteers received a single dose of the Vi conjugate vaccine (Vi-TT) and 37 received a single dose of Vi polysaccharide vaccine (Vi-PS) prior to oral challenge with live S. Typhi bacteria as part of a randomised controlled, phase 2b study. In addition to data previously published showing persistence of Vi IgG and IgA antibodies for 7 months after Vi vaccination, titres were measured at intervals until 13 months post-vaccination. Ten participants who received Vi-TT (both challenged and unchallenged) were re-vaccinated with Vi-PS at an interval of 19-23 months post-prime. Anti-Vi IgG and IgA titres, and Vi-specific antibody secreting cells and memory B cells were measured at seven days and one month post-boost. <br><strong> Findings: </strong>Vi IgG and IgA antibody titres remained significantly elevated above baseline levels 13 months after priming with Vi-TT, with a 4-fold rise retained in 90% and 88% of recipients (Vi IgG and IgA, respectively). Anti-Vi IgG and IgA antibody titres were found to persist at higher levels in participants who received a single dose of Vi-TT than in those who received Vi-PS. No significant boost in Vi-antibody titre was observed in response to oral challenge with S. Typhi bacteria, one month after vaccination. Following a Vi-PS booster vaccination in those previously vaccinated with Vi-TT, anti-Vi IgG and IgA titres were significantly elevated, with similar titres observed at one month post-boost compared with one month after primary vaccination. The frequency of Vi-specific IgA antibody secreting cells increased significantly 7 days post-boost compared with pre-boost. No memory B cell response was observed following Vi-PS booster vaccination. <br><strong> Interpretation: </strong>Strong persistence of anti-Vi IgG and IgA following Vi-TT vaccination suggests that the conjugate vaccine may offer durable protection, supporting its use in endemic settings.
spellingShingle Bentley, T
Jones, E
Jin, C
Moore, M
Gardner, J
Hill, J
Pollard, AJ
Persistence of antibody after a vi-tetanus toxoid conjugate vaccine and effect of boosting with a plain polysaccharide vaccine on Vi antibody and antigen-specific B cells
title Persistence of antibody after a vi-tetanus toxoid conjugate vaccine and effect of boosting with a plain polysaccharide vaccine on Vi antibody and antigen-specific B cells
title_full Persistence of antibody after a vi-tetanus toxoid conjugate vaccine and effect of boosting with a plain polysaccharide vaccine on Vi antibody and antigen-specific B cells
title_fullStr Persistence of antibody after a vi-tetanus toxoid conjugate vaccine and effect of boosting with a plain polysaccharide vaccine on Vi antibody and antigen-specific B cells
title_full_unstemmed Persistence of antibody after a vi-tetanus toxoid conjugate vaccine and effect of boosting with a plain polysaccharide vaccine on Vi antibody and antigen-specific B cells
title_short Persistence of antibody after a vi-tetanus toxoid conjugate vaccine and effect of boosting with a plain polysaccharide vaccine on Vi antibody and antigen-specific B cells
title_sort persistence of antibody after a vi tetanus toxoid conjugate vaccine and effect of boosting with a plain polysaccharide vaccine on vi antibody and antigen specific b cells
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