Search bioRxiv⌕ Search

bioRxiv · 10.1101/2023.08.31.555805

Immunogenicity and efficacy of a subcutaneously administered, adjuvanted vaccine containing modified S1 spike protein of SARS-CoV-2 variant C.1.2

Abstract

During the COVID-19 pandemic, vaccines have produced protective immunity sufficient enough to cause a decrease in hospitalizations and deaths; however, the pandemic continues due to mutational events, predominantly occurring in the S1 sequence of the spike protein of SARS-CoV-2. We have developed a baculovirus-expressed, modified S1 SARS-CoV-2 protein based on the C.1.2 variant, which was first identified in South Africa.1 This was encapsulated in a vitamin E containing, nonphospholipid liposome, which was then used to subcutaneously immunize Syrian hamsters. This vaccine, when administered at day 1 generates IgG responses that react to the modified C.1.2 S1 protein; full-length spike proteins from Wuhan-Hu-1, Delta, Omicron BA.1; and the Omicron recombinant variant XBB.1.5 in 100% of the animals. The second dose administered subcutaneously on day 28 demonstrated anamnestic response in the quantitative IgG assay to the Wuhan-Hu-1 spike Receptor Binding Domain (RBD). In addition, antibody IgA and IgM responses in sera were demonstrated. Serum IgG antibody responses to the spike proteins of the modified C.1.2 S1 and full-length spike proteins Wuhan-Hu-1, Delta, Omicron BA.1, and Omicron recombinant XBB.1.5 variants are elevated for over 120 days. Challenge of vaccinated and unvaccinated hamsters at day 126 of the study with an Omicron BA.1 resulted in a difference in weight change and viral load based on the qRT-PCR assay seven days after challenge.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Bowe, M. L., Wright, E. M., Pushko, P., Backstedt, B., Gardner, C., Short-Freeman, M., Kar, S., Wright, D. C.. 2023-09-01. Immunogenicity and efficacy of a subcutaneously administered, adjuvanted vaccine containing modified S1 spike protein of SARS-CoV-2 variant C.1.2. https://doi.org/10.1101/2023.08.31.555805

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Common viral infections seed regionally distinct resident memory T cells in the human CNS

T cells persist in the central nervous system (CNS) and can drive both protection and neurological disease. How these cells are organized in humans and what they recognize is largely unknown. Here, we profiled CD8 T cells across anatomically distinct CNS regions, obtained through on-site autopsies and temporal lobe resection surgeries, using single-cell RNA sequencing, paired T cell receptor sequencing, and DNA-barcoded tetramers. Resident memory T cells (TRM) specific for Epstein-Barr virus, cytomegalovirus, influenza A, and SARS-CoV-2 were identified across CNS compartments. Anatomical location was the strongest correlate of TRM cell state, with leptomeningeal cells adopting a cytokine-poised TRM program, whereas brain TRM cells were transcriptionally restrained. Cells of the same clonotype spanned tissues yet adopted local transcriptional states. Viral specificity added another layer of TRM heterogeneity with GZMK/GZMA-expressing EBV-specific populations and interferon-stimulated gene signatures in SARS-CoV-2 and Influenza A-specific cells. The human CNS thus harbors regionally distinct CD8+ TRM shaped by common viral exposures.

immunology↗

A regulatory T cell signature provides a shared molecular basis for the therapeutic window of opportunity in rheumatic disease

Rheumatic diseases, including rheumatoid arthritis (RA), spondyloarthritis (SpA) and osteoarthritis (OA), show distinct phenotypes yet respond to overlapping therapies, implicating shared immune mechanisms. In the Transimmunom cohort, we profiled peripheral blood from 240 individuals (47 healthy, 44 OA, 91 RA, 58 SpA) across deep immunophenotyping, immunoproteomics and Treg-Teff transcriptomics. Single-layer analyses revealed broader Treg than Teff remodeling, along with a shared pattern of reduced activated Tregs and expanded Helios+ Tregs across all diseases, alongside a decrease in functional Treg subpopulations, including CTLA4+ and CD45RA- Tregs. In RA specifically, LAG3+ Tregs were also expanded. Combining omics layers outperformed single-layer approaches for disease classification. Among individual layers, Treg transcriptomes were most discriminative, and integration uncovered disease-specific programs. Unsupervised clustering identified a cross-disease cluster independent of activity, treatment and age, mapping to early disease (<= years) and dominated by a Treg dysfunction-associated program. These results provide a biological rationale for the therapeutic "window of opportunity" concept and duration-stratified Treg-directed trials.

immunology↗

Inhibitory Fc Receptor sets a time limit on macrophage response to IgG

Antibodies engage both activating Fc Receptors and the inhibitory receptor Fc{gamma}RIIB. Why macrophages need a dedicated inhibitory receptor rather than simply tuning activating receptor signaling is unclear. Using DNA-based chimeric receptors and in silico modeling, we independently controlled activating and inhibitory Fc Receptors. We found that Fc{gamma}RIIB imposed a time limit on macrophage phagocytosis and ERK signaling. The time limit is due to activating Fc Receptors converting PI(4,5)P2 to PI(3,4,5)P3, which is subsequently converted to PI(3,4)P2 by Fc{gamma}RIIB. This leads to a pulse of active signaling, which is sufficient for phagocytosis of small bacteria-sized targets but not phagocytosis of large targets and TNF secretion. Unlike engaging Fc{gamma}RIIB, reducing activating Fc Receptor signaling decreased initiation of phagocytosis, the speed of PI(3,4,5)P3 generation, and the amplitude of ERK signaling. Our results demonstrate that Fc{gamma}RIIB controls the duration of IgG signaling, while the activating Fc Receptors control sensitivity.

immunology↗