Specifically modified Env immunogens activate B-cell precursors of broadly neutralizing HIV-1 antibodies in transgenic mice

By A. McGuire, M. Gray, P. Dosenovic, Alexander D. Gitlin, N. Freund, J. Petersen, C. Correnti, W. Johnsen, R. Kegel, A. Stuart and 6 more. 2016

184 citations recorded by the source corpus.

VRC01-class broadly neutralizing HIV-1 antibodies protect animals from experimental infection and could contribute to an effective vaccine response. Their predicted germline forms (gl) bind Env inefficiently, which may explain why they are not elicited by HIV-1 Env-immunization. Here we show that an optimized Env immunogen can engage multiple glVRC01-class antibodies. Furthermore, this immunogen activates naive B cells expressing the human germline heavy chain of 3BNC60, paired with endogenous mouse light chains in vivo. To address whether it activates B cells expressing the fully humanized gl3BNC60 B-cell receptor (BCR), we immunized mice carrying both the heavy and light chains of gl3BNC60. B cells expressing this BCR display an autoreactive phenotype and fail to respond efficiently to soluble forms of the optimized immunogen, unless it is highly multimerized. Thus, specifically designed Env immunogens can activate naive B cells expressing human BCRs corresponding to precursors of broadly neutralizing HIV-1 antibodies even when the B cells display an autoreactive phenotype. The induction of broadly neutralizing antibodies (bNAbs) is a goal of HIV-1 vaccine research. Here the authors demonstrate the ability of an HIV Env-derived immunogen to bind germline precursors of a class of bNAbs and to activate the corresponding B cells in a knock-in mouse model

Subfields: Immunology, Radiology, Nuclear Medicine and Imaging, Virology

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. F. Sallusto
2. A. Lanzavecchia
3. Rafi Ahmed
4. Bali Pulendran
5. V. Schirrmacher

In Radiology, Nuclear Medicine and Imaging

1. Neil P. King
2. M. Kanekiyo
3. Daniel Ellis
4. F. Sallusto
5. David Baker
6. A. Lanzavecchia
7. Frances H. Arnold

In Virology

1. Neil P. King
2. F. Sallusto
3. A. Lanzavecchia

Citations in the corpus

• Induction of Potent Neutralizing Antibody Responses by a Designed Protein Nanoparticle Vaccine for Respiratory Syncytial Virus (2019, background): “, 2015), HIV envelope (Abbott et al., 2018; He et al., 2016; Jardine et al., 2015; McGuire et al., 2016; Sliepen et al., 2015), and Epstein-Barr virus (Kanekiyo et al.”
• New Vaccine Design and Delivery Technologies (2019, methodology): “This strategy is most established in the context of HIV vaccine research, where it is primarily (though not only [61, 62]) focused on eliciting bNAbs against the CD4 binding site of HIV Env [49, 62, [69] [70] [71] .”