473. Functionality and Determinants of Antibody Responses to H1N1 pandemic Inactivated Vaccine (pH1N1 vaccine) in HIV-Infected Children and Youth
Session: Poster Abstract Session: Prevention and Treatment of Viral Infections
Thursday, October 3, 2013
Room: The Moscone Center: Poster Hall C
Posters
  • NWCS114_Poster_FINAL.pdf (252.0 kB)
  • Background: HIV infection is associated with decreased antibody responses to inactivated influenza vaccines. We investigated the antibody functionality (avidity and neutralization) and the immune determinants of antibody response to a pH1N1 inactivated vaccine.

    Methods: 90 HIV-infected subjects 4-25 -years old received two doses of pH1N1 vaccine at weeks 0 and 3 and had plasma and cells frozen at week 0 and after both doses (weeks 3 and 5).  Hemagglutinin inhibition (HAI), avidity, B-cell phenotype (flow cytometry) (N=58), pH1N1-B cell-memory (IgG ELISPOT) (N=46) were measured at all timepoints; neutralization, and pH1N1-Th1 and Th2 cytokine responses (Luminex of stimulated culture supernatants, N=72) were measured at weeks 0 and 3.

    Results: pH1N1-IgG ELISPOT values increased after vaccinations (p<0.048), which correlated with HAI (rho>0.34, p<0.03). B-cell phenotypes did not change after vaccination. pH1N1-IL2 and IL4 production increased after vaccination (p<0.005), but IFNg, IL5, IL13 and IL21 did not.

    pH1N1 antibody avidity increased after dose 2 (p=0.04). Older subjects (age >9 years) showed increases post dose 2 (p<0.04) while the younger ones did not. In addition, baseline pH1N1-seropositive subjects (HAI≥40) had the highest increases in avidity after vaccination (p<0.02). Avidity post dose 2 positively correlated with HAI titers (rho=0.28, p=0.01) and negatively with CD19+CD21-CD27-CD20+% exhausted and CD19+CD21-CD27-CD20-% transitional B cells (rho<-0.33, p=0.03).
     
    pH1N1 neutralizing antibodies increased in all age groups after vaccination (N=30, p<0.0001).  The rate of titers >40 post dose 1 was marginally predicted by IgG ELISPOT results, CD19+CD21-CD27-CD20+% exhausted cells and pH1N1-IL-2 levels (p<0.06).  In multivariable analysis, IL-2 and CD19+CD21-CD27-CD20+% independently predicted the neutralizing titers (p=0.02 and p=0.048, respectively).
     
    Conclusion: The functionality of pH1N1 antibodies in HIV-infected subjects following vaccination correlated with HAI responses, but also with the proportion of memory B cells, age, baseline serostatus and pH1N1-Th1 responses. High proportions of exhausted and transitional B cells negatively correlated with functionality.
    Donna Curtis, MD, MPH1, Petronella Muresan, MS2, Sharon Nachman, MD3, Terence Fenton, PhD2, Kelly M. Richardson, MS4, Teresa Dominguez, MS4, Pat Flynn, MD5, George Siberry, MD, MPH6, Stephen Spector, MD7, Coleen Cunningham, MD8, Anthony Bloom, BA9 and Adriana Weinberg, MD1, (1)Pediatric Infectious Diseases, University of Colorado Denver School of Medicine, Aurora, CO, (2)Harvard School of Public Health, Boston, MA, (3)SUNY Stony Brook, Stony Brook, NY, (4)University of Colorado Denver, Aurora, CO, (5)St. Jude's Children's Hospital, Memphis, TN, (6)NICHD, Bethesda, MD, (7)University of California San Diego, San Diego, CA, (8)Pediatrics, Duke University Medical Center, Durham, NC, (9)Frontier Science and Technology Research Foundation, Amherst, NY

    Disclosures:

    D. Curtis, None

    P. Muresan, None

    S. Nachman, None

    T. Fenton, None

    K. M. Richardson, None

    T. Dominguez, None

    P. Flynn, None

    G. Siberry, None

    S. Spector, None

    C. Cunningham, None

    A. Bloom, None

    A. Weinberg, None

    Findings in the abstracts are embargoed until 12:01 a.m. PST, Oct. 2nd with the exception of research findings presented at the IDWeek press conferences.