1158. Impact of HIV Infection on Avidity and Function of Pneumococcal Capsule-specific IgG After Revaccination with Polysaccharide and Conjugate Vaccines
Session: Poster Abstract Session: Innate and Adaptive Immunity to Infections
Saturday, October 22, 2011
Room: Poster Hall B1
Background: Reimmunization is targeted to limit the persistent risk of pneumococcal disease in persons with HIV.  We characterized changes in the quality of pneumococcal capsule-specific IgG (avidity and killing) following reimmunization with 23-valent polysaccharide (PPV) and 7-valent conjugate (PCV) vaccines. 

Methods: We measured the avidity of IgG to serotypes (ST) 14 and 19F before and 60 days after reimmunization with PPV or PCV among 60 adults with HIV (HIV+) who received PPV primary immunization 3-8 years earlier, and 20 seronegative HIV- control subjects (HIV-) receiving primary PCV. Avidity was determined by the moles (M) of ammonium thiocyanate required to dissociate 50% of IgG by ELISA.  Function was determined for ST 14 and PCV group by killing assays with antibody, neutrophils and complement. We compared group medians with analysis of variance and mean changes in avidity with paired t-tests.

Results: Baseline avidity for ST 14, but not 19, was higher among HIV+ with ≤350 CD4+ T cells/uL vs. HIV- (1.16 vs. 0.67 M; p=.04). Post-immunization, HIV- generated increased avidity to ST 14 (0.67 to 1.31M; p<.001) and 19 (.83 to 1.3M; p=.005) with PCV, as did HIV+ with >350 CD4+ T cells/µL for ST 14 with both vaccines (p≤ .05). HIV+ with ≤350 CD4+ showed no change in avidity for ST 14 nor did any HIV+ for ST 19. The change in avidity was higher in HIV- (PCV) vs. HIV+ (PCV/PPV) and CD4 groups (p≤.01 for all comparisons). Few (25%) HIV- but most (93%) HIV+ supported killing of ST14 prevaccination at baseline.  Reciprocal killing titers increased with PCV from median 6 to 259 (p<.001) among HIV- but HIV+ showed no rise from low baselines values.  The efficiency of antibody to support killing (Killing Index = percent kill per ug PPS14-specific IgG) was similar in all groups on day 60.

Conclusion: Limitations in both the quality and quantity of functional antibody responses to pneumococcal revaccination may limit vaccine efficacy in high-risk groups.


Subject Category: E. Innate and adaptive immunity to infections, including vaccine immunology

Jeremy Rahkola, BS1,2, Mollie Roediger, MS3,4, Kathy H. Hullsiek, PhD3,4, Anuradha Ganesan, MD5,6, Michael Landrum, MD4, Amy Weintrob, MD4, Brian Agan, MD4, Sheila Medina, MPH4, Braden Hale, MD, MPH4, Nancy Crum-Cianflone, MD MPH4 and Edward Janoff, MD1,2, (1)Mucosal and Vaccine Research Program Colorado (MAVRC) Infectious Disease, University of Colorado Denver, Aurora, CO, (2)Infectious Disease, Denver Veterans Affairs Medical Center , Denver, CO, (3)Division of Biostatistics, University of Minnesota, Minneapolis, MN, (4)Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences, Bethesda, MD, (5)Infectious Disease Clinic, National Naval Medical Center, Bethesda, MD, (6)Infectious Disease Clinical Research Program, Uniformed Services University, Bethesda, MD

Disclosures:

J. Rahkola, None

M. Roediger, None

K. H. Hullsiek, None

A. Ganesan, None

M. Landrum, None

A. Weintrob, None

B. Agan, None

S. Medina, None

B. Hale, None

N. Crum-Cianflone, None

E. Janoff, None

Findings in the abstracts are embargoed until 12:01 a.m. EST Thursday, Oct. 20 with the exception of research findings presented at IDSA press conferences.