التفاصيل البيبلوغرافية
| العنوان: |
Optimization of an alum-anchored clinical HIV vaccine candidate. |
| المؤلفون: |
Rodrigues, Kristen A., Cottrell, Christopher A., Steichen, Jon M., Groschel, Bettina, Abraham, Wuhbet, Suh, Heikyung, Agarwal, Yash, Ni, Kaiyuan, Chang, Jason Y. H., Yousefpour, Parisa, Melo, Mariane B., Schief, William R., Irvine, Darrell J. |
| المصدر: |
NPJ Vaccines; 8/12/2023, Vol. 8 Issue 1, p1-14, 14p |
| مصطلحات موضوعية: |
AIDS vaccines, B cells, IMMUNOGLOBULINS, AMINO acid sequence, GERMINAL centers, HUMORAL immunity, HIV, VACCINE development |
| مستخلص: |
In the ongoing effort to develop a vaccine against HIV, vaccine approaches that promote strong germinal center (GC) responses may be critical to enable the selection and affinity maturation of rare B cell clones capable of evolving to produce broadly neutralizing antibodies. We previously demonstrated an approach for enhancing GC responses and overall humoral immunity elicited by alum-adjuvanted protein immunization via the use of phosphoserine (pSer) peptide-tagged immunogens that stably anchor to alum particles via ligand exchange with the alum particle surface. Here, using a clinically relevant stabilized HIV Env trimer termed MD39, we systematically evaluated the impact of several parameters relevant to pSer tag composition and trimer immunogen design to optimize this approach, including phosphate valency, amino acid sequence of the trimer C-terminus used for pSer tag conjugation, and structure of the pSer tag. We also tested the impact of co-administering a potent saponin/monophosphoryl lipid A (MPLA) nanoparticle co-adjuvant with alum-bound trimers. We identified MD39 trimer sequences bearing an optimized positively-charged C-terminal amino acid sequence, which, when conjugated to a pSer tag with four phosphates and a polypeptide spacer, bound very tightly to alum particles while retaining a native Env-like antigenicity profile. This optimized pSer-trimer design elicited robust antigen-specific GC B cell and serum IgG responses in mice. Through this optimization, we present a favorable MD39-pSer immunogen construct for clinical translation. [ABSTRACT FROM AUTHOR] |
|
Copyright of NPJ Vaccines is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |
Full Text Finder