Development of highly neutralizing nanobodies against HIV-1 and SARS-CoV-2

National Institute Of Arthritis And Musculoskeletal And Skin Diseases

Investigators

Linked publications, trials & patents

Abstract

HIV-1 and -2 are lentiviruses that cause acquired immunodeficiency syndrome (AIDS) in humans. To date, no effective vaccine has been developed and according to the World Health Organization nearly 40 million people are infected with HIV across the world. Because preventive measures and treatments are not widely available, AIDS is the leading cause of death in areas such as Sub Saharan Africa. There is therefore an urgent need to develop efficient methods, including vaccines and immunotherapies to prevent HIV infection in susceptible populations. SARS-CoV-2 has caused more than 4 million deaths worldwide since the beginning of the COVID19 pandemic in December 2019. Although several successful vaccines have been deployed to date, a large fraction of the world and the US populations remain unvaccinated and thus susceptible to infection and hospitalization. In such cases, immunotherapy have been shown to prevent mortality. While several efficient anti-HIV-1 and anti-SARS-CoV-2 antibodies have been isolated from humans, camelid heavy chain only antibodies offer an exciting alternative. V(D)J domains from such antibodies, also known as nanobodies, are particularly suited to block viruses because they can target antigen crevices such as HIV glycan-shielded spikes or SARS-CoV-2 epitopes not recognized by bulkier human antibodies. Nanobodies can also be humanized with relative ease, a strategy that reduces their immunogenicity in clinical trials. This fiscal year we have isolated and characterized nanobodies against SARS-CoV-2 from llama and nanomice (nanobody producing mice we engineered). We have shown that these molecules can block viral entry in cell culture, both for the original virus as well as its new variants. On a different set of experiments, we have produced anti-HIV-1 antibodies which we are currently characterizing against a panel of HIV-1 strains.