دورية أكاديمية
Potency and durability of T and B cell immune responses after homologous and heterologous vector delivery of a trimer-stabilized, membrane-displayed HIV-1 clade ConC Env protein.
| العنوان: | Potency and durability of T and B cell immune responses after homologous and heterologous vector delivery of a trimer-stabilized, membrane-displayed HIV-1 clade ConC Env protein. |
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| المؤلفون: | Perdiguero, B., Hauser, A., Gómez, C.E., Peterhoff, D., Sideris, E., Sorzano, CÓS, Wilmschen, S., Schaber, M., Stengel, L., Asbach, B., Ding, S., Von Laer, D., Levy, Y., Pantaleo, G., Kimpel, J., Esteban, M., Wagner, R. |
| المصدر: | Frontiers in immunology, vol. 14, pp. 1270908 |
| سنة النشر: | 2023 |
| المجموعة: | Université de Lausanne (UNIL): Serval - Serveur académique lausannois |
| مصطلحات موضوعية: | Animals, Mice, HIV Antibodies, HIV-1/genetics, Membrane Proteins, env Gene Products, Human Immunodeficiency Virus/genetics, Antibodies, Neutralizing, HIV Seropositivity, AIDS Vaccines/genetics, Immunity, DNA, HIV-1 vaccine, T and B cells, VSV-GP and NYVAC vectors, membrane display, mice immunization, trimeric ConCv5 KIKO protein |
| الوصف: | The generation of an HIV-1 vaccine able to induce long-lasting protective immunity remains a main challenge. Here, we aimed to modify next-generation soluble, prefusion-stabilized, close-to-native, glycan-engineered clade C gp140 envelope (Env) trimers (sC23v4 KIKO and ConCv5 KIKO) for optimal display on the cell surface following homologous or heterologous vector delivery. A combination of the following modifications scored best regarding the preservation of closed, native-like Env trimer conformation and antigenicity when using a panel of selected broadly neutralizing (bnAb) and non-neutralizing (nnAb) monoclonal antibodies for flow cytometry: i) replacing the natural cleavage site with a native flexible linker and introducing a single amino acid substitution to prevent CD4 binding (*), ii) fusing a heterologous VSV-G-derived transmembrane moiety to the gp140 C-terminus, and iii) deleting six residues proximal to the membrane. When delivering membrane-tethered sC23v4 KIKO* and ConCv5 KIKO* via DNA, VSV-GP, and NYVAC vectors, the two native-like Env trimers provide differential antigenicity profiles. Whereas such patterns were largely consistent among the different vectors for either Env trimer, the membrane-tethered ConCv5 KIKO* trimer adopted a more closed and native-like structure than sC23v4 KIKO*. In immunized mice, VSV-GP and NYVAC vectors expressing the membrane-tethered ConCv5 KIKO* administered in prime/boost combination were the most effective regimens for the priming of Env-specific CD4 T cells among all tested combinations. The subsequent booster administration of trimeric ConCv5 KIKO* Env protein preserved the T cell activation levels between groups. The evaluation of the HIV-1-specific humoral responses induced in the different immunization groups after protein boosts showed that the various prime/boost protocols elicited broad and potent antibody responses, preferentially of a Th1-associated IgG2a subclass, and that the obtained antibody levels remained high at the memory phase. In summary, we ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1664-3224 |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/38045703; info:eu-repo/semantics/altIdentifier/eissn/1664-3224; https://serval.unil.ch/notice/serval:BIB_D789F3FAEA8ATest; urn:issn:1664-3224 |
| DOI: | 10.3389/fimmu.2023.1270908 |
| الإتاحة: | https://doi.org/10.3389/fimmu.2023.1270908Test https://serval.unil.ch/notice/serval:BIB_D789F3FAEA8ATest |
| رقم الانضمام: | edsbas.4B3ED84F |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 16643224 |
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| DOI: | 10.3389/fimmu.2023.1270908 |