CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

803 B- AND T-CELL SUBSETS AND IMMUNOGENICITY OF ROTAVIRUS VACCINE IN PHIV & PHEU INFANTS

Adriana Weinberg 1 , Jane Lindsey 2 , Ronald Bosch 2 , Deborah Persaud 3 , Paul Sato 4 , Barbara Heckman 5 , Kelly Richardson 1 , Amanda Zadzilka 6 , Margaret Nelson 7 , Myron Levin 1 1 Univ of Colorado, Aurora, CO, USA, 2 Harvard Univ, Boston, MA, USA, 3 The Johns Hopkins Univ, Baltimore, MD, USA, 4 DAIDS, NIAID, Bethesda, MD, USA, 5 Data Mgmt Cntr, Amherst, NY, USA, 6 Frontier Sci and Tech Rsr Fndn, Amherst, NY, USA, 7 Merck & Co, Inc, Upper Gwynedd, PA, USA Background: IMPAACT P1072 was a double-blind placebo-controlled study of safety and immunogenicity of pentavalent rotavirus vaccine (RV5) in perinatally HIV-infected (PHIV) and exposed uninfected (PHEU) infants. This secondary analysis reports associations of HIV status and RV5 with B and T cell subsets and correlations of subsets with RV5 antibody responses. Methods: 89 infants (23 PHIV/19 PHEU vaccine- and 24 PHIV/ 23 PHEU placebo-recipients) had activated (act), inflammatory (inflam) and regulatory (reg) B/T cells and B cell differentiation measured before vaccination, 3wks post-dose 1 (PD1), and 2wks PD3. Immunogenicity was measured by anti-RV5 IgA and anti-G1-4 and P IgG. Spearman correlations (|ρ| ≥ 0.2) were used to identify associations. Area under the curve (AUC) was calculated for markers (log10 scale) using predicted values frommixed random effects models. Results: At entry: PHIV had median HIV viral load (VL) of 33,500 c/mL and 28% CD4+ cells, and 89% had initiated cART. PHEU and PHIV did not differ significantly (p>0.05) in B/T cell subset distribution. In PHIV, VL positively correlated with act CD8+CD38+HLADR+%, CD19+IL21r+%, CD19+BAFFr+% and immature CD19+CD10+%; cART duration negatively correlated with inflam CD4+/CD8+CD17+%. In PHIV and PHEU, CD4+% and counts positively correlated with reg CD8+CD25+FOXP3+%. Among lymphocyte subsets, reg CD4+/CD8+/CD19+IL10+% and CD4+/CD8+/CD19+TGFb+% in general positively correlated with inflam CD4+/CD8+IL17+%; and act CD4+/CD8+CD38+HLADR+% positively correlated with immature CD19+CD10+%. Vaccination and HIV status were not significantly associated with differential changes in B/T cell subsets except for reg CD4+IL10+%, which increased in PHIV vaccinees and decreased in PHEU and PHIV placebo recipients. IgA and/or IgG responses to RV5 positively correlated with CD4+% and/or counts and with reg CD4+/CD8+CD25+FOXP3+%; but negatively correlated with reg CD4+IL10+%, CD4+TGFb+% and inflam CD4+IL17+% (Figure). Conclusion: We did not find reg, inflam or act B/T-cell differences between PHEU and PHIV. Higher inflam, IL10+ and TGFb+ Tregs were associated with lower responses to RV5, while CD25+FOXP3+ Tregs were associated with higher responses. IL10+ and TGFb+ B/Tregs were associated with higher Tinflam, while CD25+FOXP3+ Tregs were associated with higher CD4+ cells. This is the 1st demonstration that phenotypically distinct Tregs differ in the way they associate with immune responses to vaccination and Tinflam or Tact. 804 IMMUNOLOGICAL RESPONSE AFTER A BOOSTER DOSE OF HBV VACCINE IN HIV-INFECTED YOUTH Background: Three doses of vaccine against HBV induce the production of protective antibody (Ab) levels (>10 IU/mL) in 95-100 % of healthy children but in only 23-56% of HIV- infected children. Ab titer elicited by vaccination decreases over time in both populations with a faster slope observed in HIV+. This decline protection against HBV is known to last almost three decades after vaccination in immunocompetent children, these data are limited in HIV+ children Methods: 53 HIV+ patients (aged 8-25 years old) in whom HBV vaccination according the Italian schedule did not elicit the generation of protective Ab titers were enrolled in the study at Paediatric Infectious Diseases Unit, L. Sacco Hospital, University of Milan. All patients had undergone ART for at least 1 year; HIV viral load was undetectable in all of them, median CD4+ count 718 mm3. All patients received a booster dose of HBV vaccine (HBVAXPRO 10 micrograms i.m.). HBV-specific Ab titer, viral load and CD4 + were measured in all subjects at baseline (T0), at 1 (T1), 6 (T6) and 12 (T12) months after the booster dose. In a subgroup of 16 patients HBV-specific cell mediated immune (CMI) responses were evaluated at baseline and at T6. Results: The booster HBV vaccine dose resulted in a seroconversion rate (anti-HBs ≥ 10 IU/mL) in 51% of patients at T1, 57% at T6 and 49% at T12; seroconversion rate was significantly correlated with CD4+T lymphocyte counts at T0 and to CD4 nadir (p<0.05). HIV viral load was undetectable at each time. CMI responses were evaluated in 11 responders (HBsAb >10 IU/mL) and 5 non-responders (HBsAb <10 IU/mL). Upregulation of HBV-specific CMI compared to baseline values was observed at T6 in responders alone. Memory (p= 0.007), Effector Memory (p= 0.003), TNF a - (p= 0.041), IFN g - (p= 0.004), and granzyme-secreting CD8+ T cells (p= 0.003), Central Memory (p= 0.005) and IL2- secreting CD4+ T cells (p= 0.015) were significantly increased in responders compared to baseline values. Activated CD8+CD38+CD45RO+ T cells (p= 0.004) were significantly reduced as well at T6 in these individuals. No significant differences were observed when T0 and T6 data were compared in non responders. Conclusion: In HIV+ patients no responding to the standard HBV immunization protocol, seroconversion induced by a booster dose of vaccine (Ab titers <10 IU/mL) correlates with the development of T cell immunological memory. Alternate immunization schedules should be designed for those individuals who don’t respond even to a booster dose of vaccine 805 HPV4 VACCINE IMMUNOGENICITY/EFFECTIVENESS IN PERINATALLY HIV-INFECTED (PHIV) YOUTH Anna-Barbara Moscicki 1 , Brad Karalius 2 , Katherine Tassiopoulos 2 , Denise Jacobson 2 , Kunjal Patel 2 , Murli U. Purswani 3 , George R. Seage 2 , Tzy-Jyun Yao 2 1 Univ of California Los Angeles, Los Angeles, CA, USA, 2 Harvard Univ, Boston, MA, USA, 3 Bronx Lebanon Hosp, Bronx, NY, USA Background: HIV-infected persons are at high risk of HPV-associated cancers. Efficacy of HPV vaccine may be suboptimal in PHIV children who have lower rates of protection from other vaccines. We sought to compare HPV antibodies and effectiveness between HPV-vaccinated PHIV and perinatally HIV-exposed uninfected (PHEU) youth. Vania Giacomet 1 , Daria Trabattoni 2 , Pilar Nannini 2 , Michela Masetti 2 , Federica Forlanini 2 , Mario Clerici 3 , Gian Vincenzo Zuccotti 4 1 L. Sacco Hosp, Milan, Italy, 2 Univ of Milan, Milan, Italy, 3 Univ of Milan, Segrate, Milan, Italy, 4 Ospedale dei Bambini V. Buzzi, Milan, Italy

Poster and Themed Discussion Abstracts

CROI 2017 348