574. Safety and Immunogenicity Profile of an Adjuvanted Varicella-Zoster Virus (VZV) Subunit Candidate Vaccine in Human Immunodeficiency Virus (HIV)-Infected Adults
Session: Oral Abstract Session: Immunization of Children and Adults with Immune Deficiencies
Thursday, October 3, 2013: 3:00 PM
Room: The Moscone Center: 250-262

Background: Subjects infected with HIV are at increased risk of herpes zoster (HZ) despite the introduction of antiretroviral therapy (ART). As the live-attenuated HZ vaccine is contraindicated for immunocompromised individuals, a subunit vaccine may be an appropriate alternative. We report on the safety and immunogenicity of a new adjuvanted VZV subunit vaccine candidate administered as a 3-dose schedule to HIV-infected adults.

Methods: A Phase I/II, randomized, observer-blind, placebo-controlled study was conducted in Germany, the US, and the UK. Three cohorts of HIV-infected adults were enrolled: ART-treated with a high CD4+ T-cell count (≥200 cells/mm3; N=94), ART-treated with a low CD4+ T-cell count (50–199 cells/mm3; N=14), and ART-naïve with a high CD4+ T-cell count (≥500 cells/mm3; N=15). Subjects were randomized 3:2 to receive 3 doses of 50 mg VZV glycoprotein E (gE) combined with the liposome-based adjuvant AS01B or 3 doses of saline at months 0, 2, and 6. Serum anti-gE antibody concentrations were measured by ELISA and frequencies of gE-specific CD4+ T cells expressing ≥2 activation markers by intracellular cytokine staining. Subjects recorded solicited and unsolicited adverse events (AEs) for 7 and 30 days, respectively, after each dose (graded 1–3). Serious AEs were collected throughout the study. Results up to month 7 are presented. (Clinicaltrials.gov, NCT01165203)

Results: 1 month after the 3rd dose, anti-gE antibody concentrations and gE-specific CD4+ T-cell frequencies were significantly higher with gE/AS01B than with saline (p<0.0001; Figure). Median CMI responses peaked after the 2nd vaccine dose. In the 7 days post-vaccination, AEs were reported in 97.3% of gE/AS01B recipients (31.1% grade 3 AEs) and 65.3% of saline recipients (16.3% grade 3 AEs). Pain, the most frequent solicited local AE, was reported by 98.6% of gE/AS01B recipients. Vaccine-related systemic AEs were reported by 21.9%–60.3%. No vaccination-related serious AEs or deaths were reported. Overall, no sustained impact on HIV viral load was noted following study vaccinations.

Conclusion: The adjuvanted VZV subunit candidate vaccine gE/AS01B was immunogenic and had an acceptable safety profile in this population of HIV-infected adults.

 

 

 

Elchonon Berkowitz, PhD, Vaccines Discovery and Development, GlaxoSmithKline Vaccines, King of Prussia, PA, Edwin Dejesus, MD, IDC Research Initiative, Altamonte Springs, FL, Hans-Jürgen Stellbrink, MD, IPM Study Center, Hamburg, Germany, Jacob Lalezari, MD, Quest Clinical Res., San Francisco, CA, Stephen Kegg, MBBCh, Trafalgar Clinic, Queen Elizabeth Hospital NHS Trust, London, United Kingdom, Matthias Stoll, Professor, Zentrum Innere Medizin, Medizinische Hochschule Hannover, Hannover, Germany, Chloe Orkin, MD, Barts and The London NHS Trust, London, United Kingdom, Mohamed El Idrissi, MSc, GlaxoSmithKline Biologicals, Wavre, Belgium, Lidia Oostvogels, MD, GlaxoSmithKline Biologicals, Rixensart, Belgium and Thomas Heineman, MD/PhD, Glaxosmithkline Vaccines, King of Prussia, PA

Disclosures:

E. Berkowitz, GlaxoSmithKline Vaccines: Employee, Salary

E. Dejesus, GlaxoSmithKline Vaccines: Grant Investigator, Research grant

H. J. Stellbrink, GlaxoSmithKline Vaccines: Grant Investigator, Research grant

J. Lalezari, GlaxoSmithKline Vaccines: Grant Investigator, Research grant

S. Kegg, GlaxoSmithKline Vaccines: Grant Investigator, Research grant

M. Stoll, GlaxoSmithKline Vaccines: Grant Investigator, Research grant

C. Orkin, GlaxoSmithKline Vaccines: Grant Investigator, Research grant

M. El Idrissi, GlaxoSmithKline Vaccines: Employee, Salary

L. Oostvogels, GlaxoSmithKline Vaccines: Employee, Salary

T. Heineman, GlaxoSmithKline Vaccines: Employee, Salary

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