Messenger RNA (mRNA) vaccines have revolutionized infectious disease prevention and cancer immunotherapy due to their rapid development, potent immunogenicity, and flexible design. Central to the clinical success of mRNA vaccines, lipid nanoparticles (LNPs) function as efficient, nonviral delivery systems capable of protecting mRNA and facilitating its uptake by target cells. Recent advances have demonstrated that LNP‐formulated mRNA vaccines and therapeutics elicit robust immune responses and confer effective protection against a broad spectrum of pathogens, including viruses and bacteria. Moreover, LNP‐based therapies have shown promising therapeutic efficacy in various cancers and rare diseases, as evidenced by both preclinical models and clinical trials. This review provides a comprehensive overview of the key components, structural features, and preparation technologies of LNPs. It further discusses ongoing challenges in LNP design, such as delivery efficiency, tissue targeting, and safety, and proposes rational strategies to address these limitations. Additionally, recent progress in the analytical methods used to characterize the critical quality attributes of LNPs is highlighted. This review aims to guide the rational design of next‐generation LNPs and to support the broader application of mRNA‐based vaccines and therapeutics.

The BCG vaccine is prepared from a weakened strain of Mycobacterium bovis (M. bovis), a bacterium closely related to Mycobacterium tuberculosis (MTB), which causes tuberculosis (TB). The vaccine was developed over 13 years, from 1908 to 1921, in the French Institut Pasteur by Léon Charles Albert Calmette and Jean-Marie Camille Guérin, who named the product Bacillus Calmette–Guérin (BCG). BCG, the only licensed vaccine currently available to prevent TB, is given to infants at high risk of TB shortly after birth to protect infants and young children from pulmonary, meningeal, and disseminated TB. The BCG vaccine, one of the safest and most widely used live attenuated vaccines in the world, recently celebrated its 100th anniversary (from 1921 to 2021); its record of use in preventing TB in China is also approaching 100 years. In 2022, a new century of BCG vaccine immunization will begin. In this article, we briefly review the history of BCG vaccine use in China, describe its current status, and offer a preliminary outlook on the future of the vaccine, to provide BCG researchers with a clearer understanding of its use in China.

Since 2019, there has been a growing focus on mRNA vaccines for infectious disease prevention, particularly following the emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). mRNA vaccines offer advantages such as rapid production and the ability to induce robust cellular and antibody responses, which are essential for combating infections that require cell-mediated immunity, including Tuberculosis (TB). This review explores recent progress in TB mRNA vaccines and addresses several key areas: (1) the urgent need for new TB vaccines; (2) current advancements in TB vaccine development, and the advantages and challenges of mRNA technology; (3) the design and characteristics of TB mRNA vaccines; (4) the immunological mechanisms of TB mRNA vaccines; (5) manufacturing processes for TB mRNA vaccines; and (6) safety and regulatory considerations. This interdisciplinary review aims to provide insights for researchers working to address critical questions in TB mRNA vaccine development.

The potency of synthetic CpG-oligo-deoxynucleotides (CpG-ODNs) adjuvants in modulating the immune cell functions through the TLR pathway has been tested and reported previously. However, the cellular signaling involved in the stimulation of macrophages by natural, CpG motif-containing adjuvant and the effector functions modulated by such stimulation has not been well studied. Here, we used in vitro and ex vivo murine macrophage assay systems, and mouse model of in vivo stimulation to explore the signaling pathway and the effector functions mediated by BC01. Results show that BC01 can induce the production of TNF-α and MCP-1 in macrophages by up-regulating the activation of NF-κB and MAPKs signaling pathway, and elevated the expression of MHC-II, CD40, CD80, and CD86. Upon stimulation with BC01, the peritoneal macrophages isolated from TLR9^−/− mice produced significantly low levels of pro-inflammatory cytokines, attenuated the activation of NF-κB and MAPKs signaling pathways, and showed reduced phagocytosis. Following in vivo stimulation with BC01, the TLR9^−/− mice produced significantly lower levels of pro-inflammatory cytokines in the serum and lymph nodes showed reduced cell proliferation. These results indicate that BC01 is an efficient agonist of TLR9 that can significantly enhance the host-protective immune functions of macrophages.

Novel adjuvants and innovative combinations of adjuvants (Adjuvant Systems) have facilitated the development of enhanced and new vaccines against re-emerging and challenging pathogenic microorganisms. Nonetheless, the efficacy of adjuvants is influenced by various factors, and the same adjuvant may generate entirely different immune responses when paired with different antigens. Herein, we combined the MPXV-B6R antigen with BC02, a novel adjuvant with proprietary technology, to assess its capability to induce both cellular and humoral immunity in mouse models. Mice received two intramuscular injections of B6R-BC02, which resulted in the production of MPXV-specific IgG, IgG1, and IgG2a antibodies. Additionally, it elicited strong MPXV-specific Th1-oriented cellular immunity and persistent effector memory B-cell responses. The advantages of BC02 were further validated, including rapid initiation of the immune response, robust recall memory, and sustained immune response induction. Although the potential of immunized mice to produce serum-neutralizing antibodies against the vaccinia virus requires further improvement, the exceptional performance of BC02 as an adjuvant for the MPXV-B6R antigen has been consistently demonstrated.

A latent tuberculosis infection (LTBI) is a major source of active tuberculosis, and addressing an LTBI is crucial for the elimination of tuberculosis. The treatment of tuberculosis often requires a 6-month course of multidrug therapy, and for drug-resistant tuberculosis, a longer course of multidrug therapy is needed, which has many drawbacks. At present, vaccines are proposed as an adjunct to chemotherapy to protect populations with an LTBI and delay its recurrence. In this study, we analyzed the protective effect of a novel subunit vaccine, AEC/BC02, in a guinea pig latent infection model. Through the optimization of different chemotherapy durations and immunization times, it was found that 4 weeks of administration of isoniazid–rifampin tablets combined with three or six injections of the vaccine could significantly reduce the gross pathological score and bacterial load in organs and improve the pathological lesions. This treatment regimen had a better protective effect than the other administration methods. Furthermore, no drug resistance of Mycobacterium tuberculosis was detected after 2 or 4 weeks of administration of the isoniazid–rifampin tablets, indicating a low risk of developing drug-resistant bacteria during short-term chemotherapy. The above results provided the foundation for an AEC/BC02 clinical protocol.