Western New England Maternal Pediatric Adolescent AIDS Clinical Trials Unit
Immune System Diseases | Influenza Virus Vaccines | Pediatrics | Therapeutics | Translational Medical Research | Virus Diseases
OBJECTIVES: 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.
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Copyright © 2015 Curtis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI of Published Version
PLoS One. 2015 Mar 18;10(3):e0118567. doi: 10.1371/journal.pone.0118567. Link to article on publisher's site.
Curtis, Donna J.; Muresan, Petronella; Nachman, Sharon; Fenton, Terence; Richardson, Kelly M.; Dominguez, Teresa; Flynn, Patricia M.; Spector, Stephen A.; Cunningham, Coleen K.; Bloom, Anthony; and Weinberg, Adriana, "Characterization of functional antibody and memory B-cell responses to pH1N1 monovalent vaccine in HIV-infected children and youth" (2015). UMass Center for Clinical and Translational Science Supported Publications. 52.
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