Broad neutralization and complement-mediated lysis of HIV-1 by PEHRG214, a novel caprine anti-HIV-1 polyclonal antibody.
OBJECTIVE
To assess the potency, breadth of action, and mechanism of action of the polyclonal goat anti-HIV antibody, PEHRG214.


METHODS
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.
Verity
Erin E
EE
Department of Microbiology, Monash University, Clayton, Victoria, Australia.
Williams
Lisa A
LA
Haddad
Da'ed N
DN
Choy
Vernon
V
O'Loughlin
Chris
C
Chatfield
Catherine
C
Saksena
Nitin K
NK
Cunningham
Anthony
A
Gelder
Frank
F
McPhee
Dale A
DA
D000914:Antibodies, Viral / Q000627:therapeutic use*; D002460:Cell Line; D003165:Complement System Proteins; D005434:Flow Cytometry; D015658:HIV Infections / Q000628:therapy*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D015151:Immunoblotting
D000914:Antibodies, Viral; D003165:Complement System Proteins