Frontiers in immunology · 2025
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.
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Patel Raj S, Agrawal Babita
Аннотация
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 (LPMix) 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 LPMix 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 LPMix 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 LPMix immunized mice, demonstrated a robust proliferation response against vaccine antigens (P1-7), which were maintained up to 2 months and 7 months, after LPMix immunizations, respectively. Moreover, antigen-specific B cells and memory CD4+/CD8+ T cells were long-lived and maintained up to 7 months after LPMix 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.
METHODS: Male C57BL/6 mice (n=5 per group) were immunized intranasally twice, 14 days apart, with the LPMix 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 LPMix 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 LPMix immunized mice, demonstrated a robust proliferation response against vaccine antigens (P1-7), which were maintained up to 2 months and 7 months, after LPMix immunizations, respectively. Moreover, antigen-specific B cells and memory CD4+/CD8+ T cells were long-lived and maintained up to 7 months after LPMix 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.