Publicação
Lipophilicity is a key factor to increase the antiviral activity of HIV neutralizing antibodies
| Resumo: | The HIV broadly neutralizing antibody 2F5 targets the transiently exposed epitope in the membraneproximal external region (MPER) of HIV-1 gp41, by a two-step mechanism involving the viral membraneand this viral glycoprotein. It was recently shown that 2F5 conjugation with a cholesterol moiety outsideof the antibody paratope substantially increases its antiviral activity. Additionally, the antiviral activityof D5, a human antibody that binds to the N-terminal heptad repeat (NHR) of gp41 and lacks membranebinding, was boosted by the same cholesterol conjugation. In this work, we evaluated the membrane affin-ity of both antibodies towards membranes of different compositions, using surface plasmon resonance. Acorrelation was found between membrane affinity and antiviral activity against HIV-1. We propose thatthe conjugation of cholesterol to 2F5 or D5 allows a higher degree of antibody pre-concentration at theviral 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 toimprove the rational design of therapeutic antibodies against HIV. |
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| Autores principais: | Augusto, Marcelo T. |
| Outros Autores: | Hollmann, Axel; Troise, Fulvia; Veiga, Ana S.; Pessi, Antonello; Santos, Nuno C. |
| Assunto: | HIV-1 Antibodies Antiviral SPR Membrane |
| Ano: | 2017 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso restrito |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| Resumo: | The HIV broadly neutralizing antibody 2F5 targets the transiently exposed epitope in the membraneproximal external region (MPER) of HIV-1 gp41, by a two-step mechanism involving the viral membraneand this viral glycoprotein. It was recently shown that 2F5 conjugation with a cholesterol moiety outsideof the antibody paratope substantially increases its antiviral activity. Additionally, the antiviral activityof D5, a human antibody that binds to the N-terminal heptad repeat (NHR) of gp41 and lacks membranebinding, was boosted by the same cholesterol conjugation. In this work, we evaluated the membrane affin-ity of both antibodies towards membranes of different compositions, using surface plasmon resonance. Acorrelation was found between membrane affinity and antiviral activity against HIV-1. We propose thatthe conjugation of cholesterol to 2F5 or D5 allows a higher degree of antibody pre-concentration at theviral 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 toimprove the rational design of therapeutic antibodies against HIV. |
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