Characterization of functional antibody and memory B-cell responses to pH1N1 monovalent vaccine in HIV-infected children and youth.

We investigated immune determinants of antibody responses and B-cell memory to pH1N1 vaccine in HIV-infected children.Ninety subjects 4 to <25 years of age received two double doses of pH1N1 vaccine. Serum and cells were frozen at baseline, after each vaccination, and at 28 weeks post-immunizatio...

Full description

Bibliographic Details
Main Authors: Donna J Curtis, Petronella Muresan, Sharon Nachman, Terence Fenton, Kelly M Richardson, Teresa Dominguez, Patricia M Flynn, Stephen A Spector, Coleen K Cunningham, Anthony Bloom, Adriana Weinberg
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4364897?pdf=render
_version_ 1818363095693656064
author Donna J Curtis
Petronella Muresan
Sharon Nachman
Terence Fenton
Kelly M Richardson
Teresa Dominguez
Patricia M Flynn
Stephen A Spector
Coleen K Cunningham
Anthony Bloom
Adriana Weinberg
author_facet Donna J Curtis
Petronella Muresan
Sharon Nachman
Terence Fenton
Kelly M Richardson
Teresa Dominguez
Patricia M Flynn
Stephen A Spector
Coleen K Cunningham
Anthony Bloom
Adriana Weinberg
author_sort Donna J Curtis
collection DOAJ
description We investigated immune determinants of antibody responses and B-cell memory to pH1N1 vaccine in HIV-infected children.Ninety subjects 4 to <25 years of age received two double doses of pH1N1 vaccine. Serum and cells were frozen at baseline, after each vaccination, and at 28 weeks post-immunization. Hemagglutination inhibition (HAI) titers, avidity indices (AI), B-cell subsets, and pH1N1 IgG and IgA antigen secreting cells (ASC) were measured at baseline and after each vaccination. Neutralizing antibodies and pH1N1-specific Th1, Th2 and Tfh cytokines were measured at baseline and post-dose 1.At entry, 26 (29%) subjects had pH1N1 protective HAI titers (≥1:40). pH1N1-specific HAI, neutralizing titers, AI, IgG ASC, IL-2 and IL-4 increased in response to vaccination (p<0.05), but IgA ASC, IL-5, IL-13, IL-21, IFNγ and B-cell subsets did not change. Subjects with baseline HAI ≥1:40 had significantly greater increases in IgG ASC and AI after immunization compared with those with HAI <1:40. Neutralizing titers and AI after vaccination increased with older age. High pH1N1 HAI responses were associated with increased IgG ASC, IFNγ, IL-2, microneutralizion titers, and AI. Microneutralization titers after vaccination increased with high IgG ASC and IL-2 responses. IgG ASC also increased with high IFNγ responses. CD4% and viral load did not predict the immune responses post-vaccination, but the B-cell distribution did. Notably, vaccine immunogenicity increased with high CD19+CD21+CD27+% resting memory, high CD19+CD10+CD27+% immature activated, low CD19+CD21-CD27-CD20-% tissue-like, low CD19+CD21-CD27-CD20-% transitional and low CD19+CD38+HLADR+% activated B-cell subsets.HIV-infected children on HAART mount a broad B-cell memory response to pH1N1 vaccine, which was higher for subjects with baseline HAI≥1:40 and increased with age, presumably due to prior exposure to pH1N1 or to other influenza vaccination/infection. The response to the vaccine was dependent on B-cell subset distribution, but not on CD4 counts or viral load.ClinicalTrials.gov NCT00992836.
first_indexed 2024-12-13T21:43:02Z
format Article
id doaj.art-58cb21da90014eddb9bf98b6ebffac55
institution Directory Open Access Journal
issn 1932-6203
language English
last_indexed 2024-12-13T21:43:02Z
publishDate 2015-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj.art-58cb21da90014eddb9bf98b6ebffac552022-12-21T23:30:29ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01103e011856710.1371/journal.pone.0118567Characterization of functional antibody and memory B-cell responses to pH1N1 monovalent vaccine in HIV-infected children and youth.Donna J CurtisPetronella MuresanSharon NachmanTerence FentonKelly M RichardsonTeresa DominguezPatricia M FlynnStephen A SpectorColeen K CunninghamAnthony BloomAdriana WeinbergWe investigated immune determinants of antibody responses and B-cell memory to pH1N1 vaccine in HIV-infected children.Ninety subjects 4 to <25 years of age received two double doses of pH1N1 vaccine. Serum and cells were frozen at baseline, after each vaccination, and at 28 weeks post-immunization. Hemagglutination inhibition (HAI) titers, avidity indices (AI), B-cell subsets, and pH1N1 IgG and IgA antigen secreting cells (ASC) were measured at baseline and after each vaccination. Neutralizing antibodies and pH1N1-specific Th1, Th2 and Tfh cytokines were measured at baseline and post-dose 1.At entry, 26 (29%) subjects had pH1N1 protective HAI titers (≥1:40). pH1N1-specific HAI, neutralizing titers, AI, IgG ASC, IL-2 and IL-4 increased in response to vaccination (p<0.05), but IgA ASC, IL-5, IL-13, IL-21, IFNγ and B-cell subsets did not change. Subjects with baseline HAI ≥1:40 had significantly greater increases in IgG ASC and AI after immunization compared with those with HAI <1:40. Neutralizing titers and AI after vaccination increased with older age. High pH1N1 HAI responses were associated with increased IgG ASC, IFNγ, IL-2, microneutralizion titers, and AI. Microneutralization titers after vaccination increased with high IgG ASC and IL-2 responses. IgG ASC also increased with high IFNγ responses. CD4% and viral load did not predict the immune responses post-vaccination, but the B-cell distribution did. Notably, vaccine immunogenicity increased with high CD19+CD21+CD27+% resting memory, high CD19+CD10+CD27+% immature activated, low CD19+CD21-CD27-CD20-% tissue-like, low CD19+CD21-CD27-CD20-% transitional and low CD19+CD38+HLADR+% activated B-cell subsets.HIV-infected children on HAART mount a broad B-cell memory response to pH1N1 vaccine, which was higher for subjects with baseline HAI≥1:40 and increased with age, presumably due to prior exposure to pH1N1 or to other influenza vaccination/infection. The response to the vaccine was dependent on B-cell subset distribution, but not on CD4 counts or viral load.ClinicalTrials.gov NCT00992836.http://europepmc.org/articles/PMC4364897?pdf=render
spellingShingle Donna J Curtis
Petronella Muresan
Sharon Nachman
Terence Fenton
Kelly M Richardson
Teresa Dominguez
Patricia M Flynn
Stephen A Spector
Coleen K Cunningham
Anthony Bloom
Adriana Weinberg
Characterization of functional antibody and memory B-cell responses to pH1N1 monovalent vaccine in HIV-infected children and youth.
PLoS ONE
title Characterization of functional antibody and memory B-cell responses to pH1N1 monovalent vaccine in HIV-infected children and youth.
title_full Characterization of functional antibody and memory B-cell responses to pH1N1 monovalent vaccine in HIV-infected children and youth.
title_fullStr Characterization of functional antibody and memory B-cell responses to pH1N1 monovalent vaccine in HIV-infected children and youth.
title_full_unstemmed Characterization of functional antibody and memory B-cell responses to pH1N1 monovalent vaccine in HIV-infected children and youth.
title_short Characterization of functional antibody and memory B-cell responses to pH1N1 monovalent vaccine in HIV-infected children and youth.
title_sort characterization of functional antibody and memory b cell responses to ph1n1 monovalent vaccine in hiv infected children and youth
url http://europepmc.org/articles/PMC4364897?pdf=render
work_keys_str_mv AT donnajcurtis characterizationoffunctionalantibodyandmemorybcellresponsestoph1n1monovalentvaccineinhivinfectedchildrenandyouth
AT petronellamuresan characterizationoffunctionalantibodyandmemorybcellresponsestoph1n1monovalentvaccineinhivinfectedchildrenandyouth
AT sharonnachman characterizationoffunctionalantibodyandmemorybcellresponsestoph1n1monovalentvaccineinhivinfectedchildrenandyouth
AT terencefenton characterizationoffunctionalantibodyandmemorybcellresponsestoph1n1monovalentvaccineinhivinfectedchildrenandyouth
AT kellymrichardson characterizationoffunctionalantibodyandmemorybcellresponsestoph1n1monovalentvaccineinhivinfectedchildrenandyouth
AT teresadominguez characterizationoffunctionalantibodyandmemorybcellresponsestoph1n1monovalentvaccineinhivinfectedchildrenandyouth
AT patriciamflynn characterizationoffunctionalantibodyandmemorybcellresponsestoph1n1monovalentvaccineinhivinfectedchildrenandyouth
AT stephenaspector characterizationoffunctionalantibodyandmemorybcellresponsestoph1n1monovalentvaccineinhivinfectedchildrenandyouth
AT coleenkcunningham characterizationoffunctionalantibodyandmemorybcellresponsestoph1n1monovalentvaccineinhivinfectedchildrenandyouth
AT anthonybloom characterizationoffunctionalantibodyandmemorybcellresponsestoph1n1monovalentvaccineinhivinfectedchildrenandyouth
AT adrianaweinberg characterizationoffunctionalantibodyandmemorybcellresponsestoph1n1monovalentvaccineinhivinfectedchildrenandyouth