Intranasal SARS-CoV-2 spike-based immunisation adjuvanted with polyethyleneimine elicits mucosal and systemic humoral responses in mice

The SARS-CoV-2 pandemic continues despite the presence of effective vaccines, and novel vaccine approaches may help to reduce viral spread and associated COVID-19 disease. Current vaccine administration modalities are based on systemic needle-administered immunisation which may be suboptimal for mucosal pathogens. Here we demonstrate in a mouse model that small-volume intranasal administration of purified spike (S) protein in the adjuvant polyethylenemine (PEI) elicits robust antibody responses with modest systemic neutralisation activity. Further, we test a heterologous intranasal immunisation regimen, priming with S and boosting with RBD-Fc. Our data identify small volume PEI adjuvantation as a novel platform with potential for protective mucosal vaccine development

Pathogen-sugar interactions revealed by universal saturation transfer analysis

Many pathogens exploit host cell-surface glycans. However, precise analyses of glycan ligands binding with heavily modified pathogen proteins can be confounded by overlapping sugar signals and/or compounded with known experimental constraints. Universal saturation transfer analysis (uSTA) builds on existing nuclear magnetic resonance spectroscopy to provide an automated workflow for quantitating protein-ligand interactions. uSTA reveals that early-pandemic, B-origin-lineage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike trimer binds sialoside sugars in an "end-on" manner. uSTA-guided modeling and a high-resolution cryo-electron microscopy structure implicate the spike N-terminal domain (NTD) and confirm end-on binding. This finding rationalizes the effect of NTD mutations that abolish sugar binding in SARS-CoV-2 variants of concern. Together with genetic variance analyses in early pandemic patient cohorts, this binding implicates a sialylated polylactosamine motif found on tetraantennary N-linked glycoproteins deep in the human lung as potentially relevant to virulence and/or zoonosis

Shared sugars - parasite glycan homology in HIV-1 vaccine design

Immune tolerance to self-glycans is a host mechanism to avoid autoimmunity, which is exploited by HIV-1 coating its envelope glycoproteins with glycans to evade neutralising antibodies (nAbs). Huettner et al. describe cross-reactivity between Schistosoma mansoni glycans and HIV-1 envelope glycoprotein glycans, suggesting a strategy for induction of HIV-1 nAbs by vaccination

Glycans in HIV-1 vaccine design - engaging the shield

Glycans are repeating carbohydrate structures added as post-translational modifications (PTMs) to proteins, forming glycoproteins. Self-glycans found on human cells, and viral glycoproteins produced in host cells, are generally weakly immunogenic, which is necessary to avoid autoimmunity. This feature is exploited by many pathogenic viruses, which glycosylate surface proteins to evade or reduce immune recognition. The HIV type-1 (HIV-1) envelope glycoprotein (Env) is heavily glycosylated, which broadly acts to shield neutralisation-relevant protein surfaces with immunorecessive self-glycans to hinder B cell recognition. However, a small subset of HIV-1-infected individuals develops potent broadly neutralising antibodies (bnAbs), many of which directly engage the glycan shield. This provides hope that such antibodies could be elicited via vaccination and help to provide protective immunity. However, HIV-1 vaccine candidates have thus far failed to fully recapitulate such glycan-specific neutralising responses. In this review we consider the fundamental glycoimmunology and structural biology that underpin glycans in antibody evasion and as antibody targets and discuss potential approaches to harness glycan targeting for HIV-1 vaccine design