The predominant target of neutralizing antibody responses at the surface of HIV-1 is a complex trimeric heterodimer envelope protein (env). The high mutational rate, recombination potential and short replication cycle of HIV increases intra-patient viral diversity limiting the effectiveness of natural humoral response against env. In some rare instances (1 to10%) people living with HIV (PLWH) develop broadly neutralizing antibodies (bNAbs) over time, with the remarkable ability to cross-neutralize multiple HIV-1 clones1. Several of these bNAbs have been isolated and are under intense investigation in their potential to support prevention and cure strategies2. Interestingly, beside their capacity to directly neutralize circulating virus by preventing virus entry or cell-to-cell transmission, bNAbs can also engage cellular immune cell responses via their Fc-domain, thereby bridging the gap between adaptive and innate immune responses 3.The BioNTech RiboMab platform offers the possibility to design innovative constructs to produce in vivo highly potent and broad bNAbs from mRNA templates4.
PhD project description
In this program, we aim to generate multiple mRNA-encoded broadly neutralizing antibodies (RibobNAbs) for future clinical applications with regard to ongoing HIV-cure approaches.
We aim to design mRNA-encoded bNAbs (RibobNAbs) allowing for in vivo expression of RibobNAbs in people living with HIV (PLWH). The candidate will finalize the validation of a first RibobNAbs set in animal models. The candidate will generate and test innovative antibody designs by in vitro screening and in animal models.
Required profile of candidate
The ideal candidate will be well-versed in (human) immunology and will have experience in in vitro assays in a cell culture environment (immunological assays such as ELISA, FACS etc.)
The candidate should be familiar with molecular biology techniques and/or relevant biochemistry methodology (cloning, recombinant protein production, protein analytics such as WB, transfection etc.).
Applicants with experience in antibody work (i.e. antibody design, immunoassay with antibodies) are favored.
Previous experience in assay design and establishment is a plus.
A background in virology and/or HIV is a plus but not required.
The candidate should display high motivation and creativity for problem solving.
Proficiency in English required both written and spoken.
Proficiency in German both written and spoken is a plus.
Publications relevant to the project
Frattari GS, Caskey M, Søgaard OS. Broadly neutralizing antibodies for HIV treatment and cure approaches. Curr Opin HIV AIDS. 2023 Jul 1;18(4):157-163. doi: 10.1097/COH.0000000000000802.
Griffith SA, McCoy LE. To bnAb or Not to bnAb: Defining Broadly Neutralising Antibodies Against HIV-1. Front Immunol. 2021 Oct 19;12:708227. doi: 10.3389/fimmu.2021.708227.
Niessl J, Baxter AE, Mendoza P, Jankovic M, Cohen YZ, Butler AL, Lu CL, Dubé M, Shimeliovich I, Gruell H, Klein F, Caskey M, Nussenzweig MC, Kaufmann DE. Combination anti-HIV-1 antibody therapy is associated with increased virus-specific T cell immunity. Nat Med. 2020 Feb;26(2):222-227. doi: 10.1038/s41591-019-0747-1.
Stadler CR, Bähr-Mahmud H, Celik L, Hebich B, Roth AS, Roth RP, Karikó K, Türeci Ö, Sahin U. Elimination of large tumors in mice by mRNA-encoded bispecific antibodies. Nat Med. 2017 Jul;23(7):815-817. doi: 10.1038/nm.4356.