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Biomedical subjects

Lisa A Williams

Publications and source records attributed to Lisa A Williams.

5 recordsLinked to original sources
PubMed2006

Broad neutralization and complement-mediated lysis of HIV-1 by PEHRG214, a novel caprine anti-HIV-1 polyclonal antibody.

OBJECTIVES: To assess the potency, breadth of action, and mechanism of action of the polyclonal goat anti-HIV antibody, PEHRG214. DESIGN: Typical human antibody responses to HIV-1 infection are unable to neutralize virus efficiently, clear the infection, or prevent disease progression. However, more potent neutralizing antibodies may be capable of playing a pivotal role in controlling HIV replication in vivo. PEHRG214 is a polyclonal caprine antibody raised against purified HIV-associated proteins, such that epitopes that are immunologically silent in humans may potentially be recognized in another species. It has been administered safely to HIV-infected individuals in Phase I clinical trials. METHODS: The anti-HIV activity of PEHRG214 was assessed using neutralization and virion lysis assays. The target proteins for PEHRG214 activity were investigated using flow cytometry and by adsorption of anti-cell antibodies from the antibody cocktail. RESULTS: PEHRG214 strongly neutralized a diverse range of primary HIV-1 isolates, encompassing subtypes A to E and both CCR5 and CXCR4 phenotypes. Neutralization was enhanced by the presence of complement. PEHRG214 also induced complement-mediated lysis of all HIV-1 isolates tested, and recognized or cross-reacted with a number of host cell proteins. Lysis was abrogated by adsorption with T and/or B cells expressing GPI-linked proteins, but not by GPI-deficient B cells or red blood cells. CONCLUSIONS: PEHRG214 was found to potently neutralize and lyse HIV-1 particles. By targeting host cell proteins present in the viral envelope, which are conserved among all strains tested, PEHRG214 potentially opens up a highly novel means of eliminating circulating virus in infected individuals.

Antibodies, Viral↗
PubMed2003

A passive immunotherapy, (PE)HRG214, in patients infected with human immunodeficiency virus: a phase I study.

(PE)HRG214 (HRG) is a polyclonal antibody preparation produced by immunization of goats with purified human immunodeficiency virus (HIV) antigens. In this phase I study, HRG was administered intravenously as a single dose (1, 2, 4, 8, or 16 mg/kg) to 18 HIV-1-infected patients with CD4 cell counts >/=50 cells/microL and virus loads >/=500 copies/mL. The most frequent adverse event was a transient rash, which appeared to be both dose- and CD4 cell count-dependent. At the 16 mg/kg level, median half-life was 68.4 h, and median C(max) was 392 microg/mL, a level well above that which inhibits HIV in vitro. At that dose level, median and maximum decreases in HIV-1 RNA levels at day 8 were 0.24 log(10) and 0.58 log(10), respectively, and, at day 29, were 0.24 log(10 ) and 2.2 log(10), respectively. HRG, administered as a single dose, is reasonably well tolerated and achieves adequate plasma concentrations.

Animals↗
PubMedDate not supplied

A phase I study of the pharmacokinetics and safety of passive immunotherapy with caprine anti-HIV antibodies, (PE)HRG214, in HIV-1-infected individuals.

PURPOSE: To establish the pharmacokinetics and safety of single-dose polyclonal caprine anti-HIV antibodies ((PE)HRG214)in HIV-1-infected individuals. DESIGN: A phase 1, open-label, nonrandomized, dose-escalating study. METHOD: HIV-1-infected patients with CD4+ T-cell counts of < or =200 cells/microL and plasma HIV viral load (VL)of > or =5,000 copies/mL received a single intravenous dose of HRG. Dosing began at 6,000 U/kg HRG with proposed step-wise escalation to 96,000 U/kg. RESULTS: Eleven males were enrolled; median CD4+T-cell count and VL were 96 cells/microL and 126,200 copies/mL, respectively. HRG exhibited linear pharmacokinetics across the dosing range studied. The mean terminal elimination half-life (t(1/2)) was 136.6 +/- 44.6 hours (range, 52.6-198 h). Serum sickness occurred in one 48,000 U/kg HRG recipient. One 6,000 U/kg and two 24,000 U/kg HRG recipients developed a mild rash. Between baseline and day 60, VL remained unchanged (n = 6), increased by 0.67 log(10) copies/mL (n = 1), or declined by 0.34-1.55 log(10) copies/mL (n = 4). CONCLUSION: Single-dose HRG exhibited linear kinetics and a long half-life. Although numbers in each dosing group were very small (n = 3), HRG was generally well tolerated in doses below 48,000 U/kg. Multiple dosing with HRG in the HIV-salvage setting may be complicated by immune-complex formation.

Animals↗