Several countries have made unremitting efforts to develop an optimal vaccine in the fight against coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With the increasing occurrence of SARS-CoV-2 variants, current vaccines show decreased neutralizing activities, especially towards the Omicron variant. In this context, adding appropriate adjuvants to COVID-19 vaccines can substantially reduce the number of required doses and improve efficacy or cross-neutralizing protection. We mainly focus on research progress and achievements associated with adjuvanted COVID-19 subunit and inactivated vaccines. We further compare the advantages and disadvantages of different adjuvant formulations in order to provide a scientific reference for designing an effective strategy for future vaccine development.

The global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become more serious because of the continuous emergence of variants of concern (VOC), thus calling for the development of broad-spectrum vaccines with greater efficacy. Adjuvants play important roles in enhancing the immunogenicity of protein-based subunit vaccines. In this study, we compared the effect of three adjuvants, including aluminum, nanoparticle manganese and MF59, on the immunogenicity of three protein-based COVID-19 vaccine candidates, including RBD-Fc, RBD and S-trimer. We found that the nanoparticle manganese adjuvant elicited the highest titers of SARS-CoV-2 RBD-specific IgG, IgG1 and IgG2a, as well as neutralizing antibodies against infection by pseudotyped SARS-CoV-2 and its Delta variant. What is more, the nanoparticle manganese adjuvant effectively reduced the viral load of the authentic SARS-CoV-2 and Delta variant in the cell culture supernatants. These results suggest that nanoparticle manganese, known to facilitate cGAS-STING activation, is an optimal adjuvant for protein-based COVID-19 subunit vaccines.

Effective compound combination (ECC; i.e, 20-S-ginsenoside Rh1, astragaloside, icariin, nobiletin, and paeonol), derived from Chinese herbal medicine, significantly ameliorates chronic obstructive pulmonary disease (COPD) in rats; however, the underlying mechanisms of ECC remain largely unclear. In this study, network pharmacology analysis integrated with experimental validation was used to explore the therapeutic mechanisms of ECC against COPD. ECC targets and COPD genes and targets were identified from multiple databases, and then used for an analysis of protein–protein interaction (PPI) networks, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and biological functioning. BisoGenet was used to comprehensively analyze the hub-network. We validated the therapeutic effect and mechanisms of ECC both in vivo and in vitro. We identified 45 ECC targets, which were mainly related to inflammatory processes, such as the NOD-like and NF-kappa B signaling pathways, hematopoietic cell lineage, Th17 cell differentiation, cellular response to lipopolysaccharide, and interleukin-8 secretion. In addition, 1180 COPD genes and 70 COPD targets were identified as being involved in the biological functions associated with COPD development, such as cytokine–cytokine receptor interaction, the TNF signaling pathway, the mitogen-activated protein kinase (MAPK) signaling pathway, regulation of lymphocyte proliferation, and positive regulation of leukocyte migration. Integrative analysis of COPD genes and targets and ECC target networks revealed that 54 genes were mainly involved in the inflammatory process, such as IL-17 signaling, NF-kappa B signaling, innate immune response–activating signal transduction, and macrophage cell differentiation. Six targets (AR, ESR1, HNRNPA1, PAPR1, TP53, and VCAM1) contained in the hub-network and their four related compounds were obtained and recognized as the key molecules associated with the effects of ECC. Molecular docking validation demonstrated that four compounds could bind to six targets that interact with COPD genes. Finally, in vivo and in vitro experiments verified that ECC treatment ameliorated the symptoms of COPD in rats by improving their lung function, reducing pathological changes, and suppressing oxidative responses and pro-inflammatory cytokine secretion, while inhibiting inflammation in LPS-induced macrophages, which may be associated with NF-kappa B and MAPK signaling regulation. This study demonstrates the therapeutic mechanisms and effects of ECC on COPD via regulation of the underlying inflammatory process.

Pyroptosis, an inflammatory programmed cell death, is characterized by the caspase-mediated pore formation of plasma membranes and the release of large quantities of inflammatory mediators. In recent years, the morphological characteristics, induction mechanism and action process of pyroptosis have been gradually unraveled. As a malignant tumor with high morbidity and mortality, cervical cancer is seriously harmful to women’s health. It has been found that pyroptosis is closely related to the initiation and development of cervical cancer. In this review the mechanisms of pyroptosis and its role in the initiation, progression and treatment application of cervical cancer are summarized and discussed.