Incomplete Neutralization and Deviation from Sigmoidal Neutralization Curves for HIV Broadly Neutralizing Monoclonal Antibodies

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Antibodies that potently neutralize a broad range of circulating HIV strains have been described. These antibodies target a variety of sites on the envelope protein of HIV, three copies of which associate to form a trimer that decorate the membrane surface of the virus particle. Some of these antibodies target regions of the envelope protein close to the membrane, some bind to the top of the trimer, others bind via carbohydrates which cover the envelope protein and another subset binds to the same site as the human HIV receptor CD4. Despite effectively blocking 50% of infection at low antibody concentrations, for some particular virus/antibody combinations a proportion of virus particles are resistant to antibody neutralization, even at extremely high concentrations. This phenomenon is called incomplete neutralization and also frequently results in non-sigmoidal dose-response curves when antibody concentration is plotted against the level of virus infection. Previously, antibodies that target the apex of the trimer have been associated with incomplete neutralization and non-sigmoidal curves. In this study we show that representatives from all the groups of antibodies described above result in incomplete neutralization against at least one virus but that the phenomenon is more frequent for those binding the apex and the stalk of the trimer. Resistant populations of virus were seen whether the virus was produced in the natural target of HIV infection (human CD4+ T cells) or engineered human cells more commonly used to produce virus to test antibody function. Understanding this phenomenon is important for the future use of antibodies as therapeutics and for vaccine studies as a resistant population of viruses could result in failure to control the virus infection in patients.

Vyšlo v časopise: Incomplete Neutralization and Deviation from Sigmoidal Neutralization Curves for HIV Broadly Neutralizing Monoclonal Antibodies. PLoS Pathog 11(8): e32767. doi:10.1371/journal.ppat.1005110
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005110

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