The recent emergence of the Omicron variant has raised concerns on vaccine efficacy and the urgent need to study more efficient vaccination strategies. Here we observed that an mRNA vaccine booster in individuals vaccinated with two doses of inactivated vaccine significantly increased the plasma level of specific antibodies that bind to the receptor-binding domain (RBD) or the spike (S) ectodomain (S1 + S2) of both the G614 and the Omicron variants, compared to two doses of homologous inactivated vaccine. The level of RBD- and S-specific IgG antibodies and virus neutralization titers against variants of concern in the heterologous vaccination group were similar to that in individuals receiving three doses of homologous mRNA-vaccine or a boost of mRNA vaccine after infection, but markedly higher than that in individuals receiving three doses of a homologous inactivated vaccine. This heterologous vaccination regime furthermore significantly enhanced the RBD-specific memory B cell response and S1-specific T cell response, compared to two or three doses of homologous inactivated vaccine. Our study demonstrates that mRNA vaccine booster in individuals vaccinated with inactivated vaccines can be highly beneficial, as it markedly increases the humoral and cellular immune responses against the virus, including the Omicron variant.

Intestinal bifidobacteria benefit human health by promoting and modulating the gut flora, and boosting therapeutic efficiency for chronic metabolic diseases and cancer. Recently, Bifidobacterium adolescentis strains with high adhesion to intestinal epithelial cells were associated with induction of T-helper 17 (Th17) cells in humans and rodents. Here, two B. adolescentis strains with similar adhesive ability but different aggregation properties were investigated for specific immunoregulatory effects, including the underlying cellular pathway, on macrophage and T-regulatory (Treg)/Th17 axis activation in vitro and in the colon of dextran sodium sulfate (DSS)-colitis mice in vivo. In-vitro, the auto-aggregative B. adolescentis strain IF1-11 induced significantly higher IL-6 and lower IL-10 secretion from immune cells, and it induced abundant Th17 cells. The non-aggregating strain IF1-03 induced significantly higher IL-10, less IL-6 and a high proportion of Treg/Th17 cells compared to total T cells. In vivo, orally administered IF1-03 protected DSS-colitis mice via activation of dendritic cells or macrophages and skewing of Treg/Th17 cells, consistent with Treg cell induction in vitro. IF1-03 exopolysaccharides showed a functional recognition pattern similar to IF1-03 for IL-10 cytokine secretion and Treg cell-differentiation induction, both dependent on the toll-like receptor 2–ERK/p38 MAPK-signaling cascade for macrophage activation. We suggest that B. adolescentis exopolysaccharide-associated enterocyte adhesion/aggregation phenotypes determine strain-specific adaptive immune responses in the gut via the macrophage-regulated Treg/Th17 axis.

Information concerning the longevity of immunity to SARS-CoV-2 following natural infection may have considerable implications for durability of immunity induced by vaccines. Here, we monitored the SARS-CoV-2 specific immune response in COVID-19 patients followed up to 15 months after symptoms onset. Following a peak at day 15–28 postinfection, the IgG antibody response and plasma neutralizing titers gradually decreased over time but stabilized after 6 months. Compared to G614, plasma neutralizing titers were more than 8-fold lower against variants Beta, Gamma, and Delta. SARS-CoV-2-specific memory B and T cells persisted in the majority of patients up to 15 months although a significant decrease in specific T cells, but not B cells, was observed between 6 and 15 months. Antiviral specific immunity, especially memory B cells in COVID-19 convalescent patients, is long-lasting, but some variants of concern may at least partially escape the neutralizing activity of plasma antibodies.

Bifidobacteria are members of the human gut microbiota and have shown to exert beneficial effects on their host. Certain strains have a long history of safe and effective use as probiotics. Due to the lack of efficient genetic tools, however, little is known about the molecular mechanisms on which these health-promoting properties are based, thus limiting the synthetic biology applications in bifidobacteria. Here, we discuss the recent development of genetic tools and their engagement in engineering bifidobacteria for food and biomedical applications, from eliminating antibiotic resistance mobile elements and improving robustness to preventing pathogen infections and delivering therapeutics for cancer treatment. In addition, we highlight the application of emerging genome engineering techniques for manipulating the bifidobacterial genome. Finally, we provide our perspective on the future development of synthetic biology techniques and programmed probiotic bifidobacteria with enhanced robustness and designer functionalities.