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| Title | A combined adjuvant approach primes robust germinal center responses and humoral immunity in non-human primates. |
|---|---|
| Journal, issue, pages | Nat Commun, Vol. 14, Issue 1, Page 7107, Year 2023 |
| Publish date | Nov 4, 2023 |
 Authors | Ivy Phung / Kristen A Rodrigues / Ester Marina-Zárate / Laura Maiorino / Bapi Pahar / Wen-Hsin Lee / Mariane Melo / Amitinder Kaur / Carolina Allers / Marissa Fahlberg / Brooke F Grasperge / Jason P Dufour / Faith Schiro / Pyone P Aye / Paul G Lopez / Jonathan L Torres / Gabriel Ozorowski / Saman Eskandarzadeh / Michael Kubitz / Erik Georgeson / Bettina Groschel / Rebecca Nedellec / Michael Bick / Katarzyna Kaczmarek Michaels / Hongmei Gao / Xiaoying Shen / Diane G Carnathan / Guido Silvestri / David C Montefiori / Andrew B Ward / Lars Hangartner / Ronald S Veazey / Dennis R Burton / William R Schief / Darrell J Irvine / Shane Crotty /  |
| PubMed Abstract | Adjuvants and antigen delivery kinetics can profoundly influence B cell responses and should be critically considered in rational vaccine design, particularly for difficult neutralizing antibody ...Adjuvants and antigen delivery kinetics can profoundly influence B cell responses and should be critically considered in rational vaccine design, particularly for difficult neutralizing antibody targets such as human immunodeficiency virus (HIV). Antigen kinetics can change depending on the delivery method. To promote extended immunogen bioavailability and to present antigen in a multivalent form, native-HIV Env trimers are modified with short phosphoserine peptide linkers that promote tight binding to aluminum hydroxide (pSer:alum). Here we explore the use of a combined adjuvant approach that incorporates pSer:alum-mediated antigen delivery with potent adjuvants (SMNP, 3M-052) in an extensive head-to-head comparison study with conventional alum to assess germinal center (GC) and humoral immune responses. Priming with pSer:alum plus SMNP induces additive effects that enhance the magnitude and persistence of GCs, which correlate with better GC-T cell help. Autologous HIV-neutralizing antibody titers are improved in SMNP-immunized animals after two immunizations. Over 9 months after priming immunization of pSer:alum with either SMNP or 3M-052, robust Env-specific bone marrow plasma cells (BM B) are observed. Furthermore, pSer-modification of Env trimer reduce targeting towards immunodominant non-neutralizing epitopes. The study shows that a combined adjuvant approach can augment humoral immunity by modulating immunodominance and shows promise for clinical translation. |
 External links | Nat Commun / PubMed:37925510 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 25.0 - 30.0 Å |
| Structure data |  EMDB-40242: BG505 MD39 SOSIP in complex with Rh.NJ85 wk12 gp120GH, N611/FP, and base epitope polyclonal antibodies  EMDB-40243: BG505 MD39 SOSIP in complex with Rh.NJ86 wk12 V1V3, C3V5, N611/FP, and base epitope polyclonal antibodies  EMDB-40244: BG505 MD39 SOSIP in complex with Rh.NJ76 wk12 C3V5, N611/FP, and base epitope polyclonal antibodies  EMDB-40252: BG505 MD39 SOSIP in complex with Rh.NK04 wk12 gp120 glycan hole and base epitope polyclonal antibodies  EMDB-40254: BG505 MD39 SOSIP in complex with Rh.NJ75 wk12 gp120 glycan hole and base epitope polyclonal antibodies  EMDB-40255: BG505 MD39 SOSIP in complex with Rh.NJ87 wk12 C3V5 and base epitope polyclonal antibodies  EMDB-40256: BG505 MD39 SOSIP in complex with Rh.NJ84 wk12 V1V3, gp120 glycan hole and base epitope polyclonal antibodies  EMDB-40257: BG505 MD39 SOSIP in complex with Rh.NJ77 wk12 V1V3, C3V5, N611/FP and base epitope polyclonal |
| Source |
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Macaca mulatta (Rhesus monkey)
