Lipophilicity is a key factor to increase the antiviral activity of HIV neutralizing antibodies

Authors
Augusto, Marcelo T.; Hollmann, Axel; Troise, Fulvia; Veiga, Ana S.; Pessi, Antonello; Santos, Nuno C.
Publication Year
2017
Language
English
Format
article
Status
Published version
Description
The HIV broadly neutralizing antibody 2F5 targets the transiently exposed epitope in the membrane proximal external region (MPER) of HIV-1 gp41, by a two-step mechanism involving the viral membrane and this viral glycoprotein. It was recently shown that 2F5 conjugation with a cholesterol moiety outside of the antibody paratope substantially increases its antiviral activity. Additionally, the antiviral activity of D5, a human antibody that binds to the N-terminal heptad repeat (NHR) of gp41 and lacks membrane binding, was boosted by the same cholesterol conjugation. In this work, we evaluated the membrane affinity of both antibodies towards membranes of different compositions, using surface plasmon resonance. A correlation was found between membrane affinity and antiviral activity against HIV-1. We propose that the conjugation of cholesterol to 2F5 or D5 allows a higher degree of antibody pre-concentration at the viral membrane. This way, the antibodies become more available to bind efficiently to the gp41 epitope, blocking viral fusion faster than the unconjugated antibody. These results set up a relevant strategy to improve the rational design of therapeutic antibodies against HIV.
Fil: Augusto, Marcelo T.. Universidade de Lisboa; Portugal
Fil: Hollmann, Axel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidade de Lisboa; Portugal
Fil: Troise, Fulvia. CEINGE Biotecnologie Avanzate S.C.R.L; Italia
Fil: Veiga, Ana S.. Universidade de Lisboa; Portugal
Fil: Pessi, Antonello. PeptiPharma; Italia
Fil: Santos, Nuno C.. Universidade de Lisboa; Portugal
Subject
ANTIBODIES
ANTIVIRAL
HIV-1
MEMBRANE
SPR
Otras Ciencias Biológicas
Ciencias Biológicas
CIENCIAS NATURALES Y EXACTAS
Access level
Restricted access
License
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repository
CONICET Digital (CONICET)
Institution
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identifier
oai:ri.conicet.gov.ar:11336/53065