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dc.contributor.authorCurtis, Donna J.
dc.contributor.authorMuresan, Petronella
dc.contributor.authorNachman, Sharon
dc.contributor.authorFenton, Terence
dc.contributor.authorRichardson, Kelly M.
dc.contributor.authorDominguez, Teresa
dc.contributor.authorFlynn, Patricia M.
dc.contributor.authorSpector, Stephen A.
dc.contributor.authorCunningham, Coleen K.
dc.contributor.authorBloom, Anthony
dc.contributor.authorWeinberg, Adriana
dc.date2022-08-11T08:11:03.000
dc.date.accessioned2022-08-23T17:30:15Z
dc.date.available2022-08-23T17:30:15Z
dc.date.issued2015-03-18
dc.date.submitted2015-10-27
dc.identifier.citationPLoS One. 2015 Mar 18;10(3):e0118567. doi: 10.1371/journal.pone.0118567. <a href="http://dx.doi.org/10.1371/journal.pone.0118567">Link to article on publisher's site</a>.
dc.identifier.issn1932-6203 (Linking)
dc.identifier.doi10.1371/journal.pone.0118567
dc.identifier.pmid25785995
dc.identifier.urihttp://hdl.handle.net/20.500.14038/50481
dc.description<p>Participating study sites and personnel include the Western New England Maternal Pediatric Adolescent AIDS Clinical Trials Unit (Katherine Luzuriaga, MD; Jesica Pagano-Therrien, RN, NP; CTSA Grant: UL1RR031982).</p>
dc.description.abstractOBJECTIVES: We investigated immune determinants of antibody responses and B-cell memory to pH1N1 vaccine in HIV-infected children. METHODS: 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. RESULTS: 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 /=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, IFNgamma, 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 IFNgamma 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. CONCLUSIONS: 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. TRIAL REGISTRATION: ClinicalTrials.gov NCT00992836.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=25785995&dopt=Abstract">Link to Article in PubMed</a>
dc.rightsCopyright © 2015 Curtis et al. This is an open access article distributed under the terms of the <a href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</a>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectUMCCTS funding
dc.subjectImmune System Diseases
dc.subjectInfluenza Virus Vaccines
dc.subjectPediatrics
dc.subjectTherapeutics
dc.subjectTranslational Medical Research
dc.subjectVirus Diseases
dc.titleCharacterization of functional antibody and memory B-cell responses to pH1N1 monovalent vaccine in HIV-infected children and youth
dc.typeJournal Article
dc.source.journaltitlePloS one
dc.source.volume10
dc.source.issue3
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1051&amp;context=umccts_pubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/umccts_pubs/52
dc.identifier.contextkey7770027
refterms.dateFOA2022-08-23T17:30:15Z
html.description.abstract<p>OBJECTIVES: We investigated immune determinants of antibody responses and B-cell memory to pH1N1 vaccine in HIV-infected children.</p> <p>METHODS: 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.</p> <p>RESULTS: 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 /=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, IFNgamma, 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 IFNgamma 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.</p> <p>CONCLUSIONS: 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.</p> <p>TRIAL REGISTRATION: ClinicalTrials.gov NCT00992836.</p>
dc.identifier.submissionpathumccts_pubs/52
dc.contributor.departmentCenter for Clinical and Translational Science
dc.source.pagese0118567


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Copyright © 2015 Curtis et al. This is an open access article distributed under the terms of the <a href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</a>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Except where otherwise noted, this item's license is described as Copyright © 2015 Curtis et al. This is an open access article distributed under the terms of the <a href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</a>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.