Journal Article Epublish 1 citation
PubMed: 40791594 DOI: 10.3389/fimmu.2025.1619882
Mixed lipopeptide-based mucosal vaccine elicits a long-term bone marrow memory response that is potentially cross-reactive against a broad-spectrum of coronaviruses in mice.
Front Immunol 16:1619882
Authors: Raj S Patel, Babita Agrawal
Affiliations
- Department of Surgery, Faculty of Medicine and Dentistry, College of Health Sciences, University Alberta, Edmonton, AB, Canada.
Abstract
Introduction
SARS-CoV-2 is continuing to prevail as an endemic virus, and therefore, we need a next-generation vaccine that prevents SARS-CoV-2 infections, broadly protects against multiple CoVs, and induces long-term local and systemic immunity. To address that need, we have designed a mixed lipopeptide-based pan-coronavirus (LP Mix) vaccine based on T and B cell epitopes derived from highly conserved and functional regions of the SARS-CoV-2 spike (S), nucleocapsid (N), and membrane (M) proteins.
Methods
Male C57BL/6 mice (n=5 per group) were immunized intranasally twice, 14 days apart, with the LP Mix vaccine candidates, which consisted of seven lipopeptides (LP1-LP7), with or without HKCC (heat-killed Caulobacter crescentus), a novel mucosal adjuvant. At 2.5 weeks, 2 months, and 7 months post-immunization, lung, spleen, bone marrow, and bronchoalveolar lavage (BAL) samples were collected for immunological analyses. Additionally, blood samples were collected monthly to monitor antibody titers.
Results
We demonstrate that intranasal immunizations of mice with LP Mix induced a long-lasting systemic IgM/IgG, and mucosal IgA response against a broad-spectrum of CoVs, showing clinically significant levels of neutralizing antibody titers. Splenocytes and bone marrow cells, derived from LP Mix immunized mice, demonstrated a robust proliferation response against vaccine antigens (P 1-7), which were maintained up to 2 months and 7 months, after LP Mix immunizations, respectively. Moreover, antigen-specific B cells and memory CD4 +/CD8 + T cells were long-lived and maintained up to 7 months after LP Mix immunizations, in the lungs, spleen and bone marrow. The addition of HKCC (heat-killed Caulobacter crescentus), a novel mucosal adjuvant, promoted the longevity of memory CD4 +/CD8 + T cell and B cell responses.
Discussion
Overall, our study demonstrates that a mucosal lipopeptide-based vaccine targeting conserved SARS-CoV-2 epitopes elicits durable, long-lasting immune responses against a broad range of coronaviruses.
MeSH
Lipopeptides, Cells, Coronavirus, Lung, Immunization, Epitopes, Bone Marrow, Vaccines, Immunity, Mucosal, Immune System Diseases, Immunologic Memory, Viruses, Immunity, Memory, Spleen, B-Lymphocytes