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PLoS One. 2015 Mar 18;10(3):e0118567. doi: 10.1371/journal.pone.0118567. eCollection 2015.

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

Author information

1
Pediatric Infectious Diseases, University of Colorado School of Medicine, Aurora, Colorado, United States of America.
2
Statistical and Data Analysis Center, Harvard School of Public Health, Boston, Massachusetts, United States of America.
3
SUNY Stony Brook, Stony Brook, New York, United States of America.
4
St. Jude's Children's Hospital, Memphis, Tennessee, United States of America.
5
University of California San Diego, La Jolla, California, and Rady Children's Hospital, San Diego, California, United States of America.
6
Duke University Medical Center, Durham, North Carolina, United States of America.
7
Frontier Science and Technology Research Foundation, Amherst, New York, United States of America.
8
Pediatric Infectious Diseases, University of Colorado School of Medicine, Aurora, Colorado, United States of America; Departments of Medicine and Pathology, University of Colorado School of Medicine, Aurora, Colorado, United States of America.

Abstract

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<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.

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.

PMID:
25785995
PMCID:
PMC4364897
DOI:
10.1371/journal.pone.0118567
[Indexed for MEDLINE]
Free PMC Article

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