Molecular Evolution of Broadly Neutralizing Llama Antibodies to the CD4-Binding Site of HIV-1

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Developing a vaccine against HIV-1 is a priority, but it remains unclear whether immunizations in humans can elicit potent broadly neutralizing antibodies able to prevent HIV-1 transmission. Llamas possess heavy chain only antibodies and conventional heavy and light chain antibodies. We previously reported the heavy chain only antibody J3, which potently neutralizes more than 95% of HIV strains, and was induced by immunization. Here we immunized two further llamas and elicited three novel broadly neutralizing heavy chain only antibodies, which were identified by high-throughput screening. These neutralizing llama antibodies target different areas of the CD4-binding site of the virus, therefore breadth and potency are increased when they are used in combination. To gain greater understanding of how the llama immunizations worked, deep sequencing of the HIV binding region of the antibodies was performed. This revealed that the antibodies were matured fully only in response to the protein immunogens. Furthermore, the VHH elicited in different animals, while sharing functional hallmarks, were encoded by distinct sequences and thus could not have been identified by a deep sequencing analysis alone. Our results show that immunization can potentially induce protective antibodies in llamas and provide a method to more extensively evaluate immunization studies.

Vyšlo v časopise: Molecular Evolution of Broadly Neutralizing Llama Antibodies to the CD4-Binding Site of HIV-1. PLoS Pathog 10(12): e32767. doi:10.1371/journal.ppat.1004552
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004552

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