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Antibodies, Neutralizing / Vaccines, Synthetic / BCG Vaccine · Journal article
Human Vaccines & Immunotherapeutics · July 9, 2026
Encouraging direction, but not yet definitive.
This preclinical mechanistic study demonstrates that heterologous prime-boost vaccination with recombinant BCG expressing chimeric SARS-CoV-2 epitopes (rBCG/rChimera+Alum) induces T cell-dependent cross-variant protection against JN.1 in K18-hACE2 transgenic mice, independent of neutralizing antibodies. The findings suggest that CD4+ and CD8+ T cell responses, enhanced macrophage activation, and IFN-γ production are key protective mechanisms, with potential implications for next-generation COVID-19 vaccine design.
Preclinical mechanistic study using genetically modified knockout mice. K18-hACE2 transgenic mice crossed with CD4−/−, CD8−/−, μMT (B cell-deficient), and IFN-γ−/− knockout strains; 6–8 weeks old; housed under standard laboratory conditions.. Intervention: Heterologous prime-boost vaccination: priming with recombinant BCG expressing chimeric SARS-CoV-2 protein (rChimera incorporating spike and nucleocapsid epitopes), followed by boost with rChimera in association with alum adjuvant.. Compared with: Unvaccinated control animals (immune compartment-matched knockout strains). Brazil (University of São Paulo, Institut Pasteur de São Paulo, Instituto Butantã), with reference to Jackson Laboratory mouse strains..
Vaccinated B lymphocyte-deficient (μMT) mice showed reduced viral loads despite lack of neutralizing antibodies, indicating humoral immunity is not the predominant protective mechanism CD4+ and CD8+ T cell-deficient animals exhibited loss of vaccine-associated protection, supporting important T cell contribution to viral control Immunized IFN-γ knockout mice revealed only partial protection, suggesting IFN-γ contributes to but is not strictly required for vaccine-induced immunity
Safety was not reported in the material analysed. Check the source before drawing any conclusion about harm.
This work identifies T cell-mediated immunity as central to cross-variant protection by an rBCG platform, suggesting a potential strategy for broad COVID-19 vaccine development. However, translation to human efficacy and safety requires clinical evaluation.
A mechanistic study using genetically modified mouse models demonstrating that T cell-associated immunity from a heterologous rBCG/protein vaccine confers cross-variant protection against SARS-CoV-2 JN.1, with clear immunological endpoints but limited to preclinical animal models.
As stated by the source record.
Quoted from the source exactly as published.
This work identifies T cell-mediated immunity as central to cross-variant protection by an rBCG platform, suggesting a potential strategy for broad COVID-19 vaccine development. However, translation to human efficacy and safety requires clinical evaluation.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
Previously, we have developed a recombinant BCG-based vaccine (rBCG) expressing a chimeric protein with spike and nucleocapsid epitopes (rChimera) to combine BCG's innate immune training capacity with SARS-CoV-2-specific adaptive immune responses. The heterologous prime-boost rBCG/rChimera+Alum regimen induced strong humoral and cellular immunity, conferring protection against the ancestral Wuhan strain in K18-hACE2 mice. Here, we used knockout mice lacking functional B cells, CD4+, or CD8+ T lymphocytes expressing hACE2 to uncover the mechanisms of anti-viral immune protection, while also evaluating vaccine efficacy against JN.1. Vaccination induced high titers of anti-rChimera antibodies with modest neutralizing capacity against the Wuhan SARS-CoV-2 strain. Nonetheless, vaccinated B lymphocyte KO mice still showed reduced viral loads, suggesting that humoral immunity may not represent the predominant protective mechanism in this model. Vaccinated mice displayed a strong Th1-biased cellular profile characterized by increased IFN-γ production and multifunctional CD4+ T cell responses, alongside activated CD8+ T cells responses. CD4+ and CD8+ T cell-deficient animals exhibited loss of vaccine-associated protection, supporting an important contribution of T cells to viral control. Additionally, immunized IFN-γ knockout mice revealed only partial protection, suggesting that IFN-γ contributes to, but is not strictly required, for vaccine-induced immunity. We also observed that macrophages derived from vaccinated animals displayed enhanced inflammatory responsiveness following heterologous stimulation. Remarkably, vaccination conferred cross-protection against JN.1, despite lack of neutralization antibodies. These findings indicate that rBCG/rChimera+Alum vaccination induces an integrated innate and predominant T cell protective immunity cross-reactive with JN.1, supporting the rBCG-based platforms as a promising approach for COVID-19 vaccine development.
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