Vaccine elicitation of HIV broadly neutralizing antibodies from engineered B cells.
Deli HuangJenny Tuyet TranAlex OlsonThomas VollbrechtMary TenutaMariia V GurylevaRoberta P FullerTorben SchiffnerJustin R AbadejosLauren CouvretteTanya R BlaneKaren SayeWenjuan LiElise LandaisAlicia Gonzalez-MartinWilliam R SchiefBen MurrellDennis R BurtonDavid NemazeeJames E VossPublished in: Nature communications (2020)
HIV broadly neutralizing antibodies (bnAbs) can suppress viremia and protect against HIV infection. However, their elicitation is made difficult by low frequencies of appropriate precursor B cell receptors and the complex maturation pathways required to generate bnAbs from these precursors. Antibody genes can be engineered into B cells for expression as both a functional antigen receptor on cell surfaces and as secreted antibody. Here, we show that HIV bnAb-engineered primary mouse B cells can be adoptively transferred and vaccinated in immunocompetent mice resulting in the expansion of durable bnAb memory and long-lived plasma cells. Somatic hypermutation after immunization indicates that engineered cells have the capacity to respond to an evolving pathogen. These results encourage further exploration of engineered B cell vaccines as a strategy for durable elicitation of HIV bnAbs to protect against infection and as a contributor to a functional HIV cure.
Keyphrases
- antiretroviral therapy
- hiv positive
- hiv infected
- hiv testing
- human immunodeficiency virus
- hepatitis c virus
- hiv aids
- men who have sex with men
- induced apoptosis
- south africa
- single cell
- cell cycle arrest
- staphylococcus aureus
- escherichia coli
- oxidative stress
- dengue virus
- working memory
- cystic fibrosis
- cell therapy
- endoplasmic reticulum stress
- biofilm formation
- insulin resistance
- genome wide identification