Outperforms Bacterial & Nano Vaccines! Anchored Yeast Vaccine Fixes the Weak-IgA Bottleneck of Mucosal Platforms

Title: Orally Antigen-Engineered Yeast Vaccine Elicits Robust Intestinal Mucosal Immunity

Journal: ACS Nano (IF 16)

DOI: https://doi.org/10.1021/acsnano.4c14690

Absin reagent: Recombinant SARS-CoV-2 Spike RBD Protein (abs05113)

1. Background: bottlenecks and breakthroughs in mucosal-vaccine development

Mucosae constitute the primary physical and immunological barrier against invading pathogens, with the intestinal mucosa representing the largest interface between host and environment. Conventional mucosal vaccines, however, are hampered by low antigen-display efficiency and inadequate adjuvant safety, and thus fail to simultaneously trigger innate and adaptive mucosal immunity.

The authors therefore exploited the Pichia pastoris expression system: yeast β-glucans act as natural, self-adjuvanting pathogen-associated molecular patterns (PAMPs), while the eukaryotic machinery enables authentic glycosylation of viral antigens. Two modalities—antigen-anchored (YVm) and secreted (YVs) yeast vaccines—were engineered to display or secrete the SARS-CoV-2 receptor-binding domain (RBD) and to dissect the optimal strategy for mucosal immunization.

2. Research pipeline: from vaccine construction to mechanistic dissection

The study followed an integrated workflow—“vaccine design → in-vitro characterization → in-vivo biodistribution → immunogenicity → mechanistic analysis → benchmarking”—to validate the superiority of the anchored yeast vaccine:

1. Vaccine construction: RBD was either GPI-anchored to the yeast surface (YVm) or secreted via an α-factor signal peptide (YVs).
2. In-vitro validation: expression, glycosylation status, gastrointestinal stability, and bone-marrow-derived dendritic-cell (BMDC) maturation were assessed.
3. Biodistribution: DiD-labelled yeasts were tracked in the small intestine, Peyer’s patches (PPs) and mesenteric lymph nodes (MLNs).
4. Immunogenicity: RBD-specific IgA/IgG titres and pseudovirus-neutralising activity were quantified.
5. Mechanistic insight: single-cell RNA-seq and bulk transcriptomics delineated DC–Tfh–B-cell crosstalk.
6. Benchmarking: YVm was compared with bacterium-anchored vaccine (BVm) and cell-membrane-biomimetic nanovaccine (CNV).

3. Key findings: anchored yeast vaccine elicits potent mucosal immunity

4. Critical contribution of Absin reagents

Throughout the study, Absin recombinant SARS-CoV-2 RBD protein (cat. abs05113) served as the gold-standard reference:

1. Positive control for Western blot: 50 ng Absin RBD enabled precise calibration of expression level and molecular mass.
2. Calibration of antigen-activity assays: ACE2-binding and gastrointestinal-stability assays were standardised against Absin RBD, ensuring inter-assay comparability.

The high purity and bioactivity of Absin RBD guaranteed reliable antigen validation, accelerating the iterative optimisation of the yeast-vaccine platform.

5. Implications and translational outlook

This work provides the first direct evidence that antigen-display modality dictates the immunogenicity of yeast-based mucosal vaccines, and establishes an anchor-and-display strategy that integrates natural adjuvanticity with authentic glycosylation. The pivotal use of Absin reagents underscores how high-quality biologics empower cutting-edge vaccine research.

Content is based on the article published in ACS Nano (DOI: 10.1021/acsnano.4c14690). All original figures and data are the intellectual property of the journal and the authors. If any infringement is identified, please contact us for prompt removal.