In-stent restenosis and stented-territory infarction after carotid and vertebrobasilar artery stenting.

BACKGROUND: Prognosis after vertebrobasilar stenting (VBS) may differ from that after carotid artery stenting (CAS). Here, we directly compared the incidence and predictors of in-stent restenosis and stented-territory infarction after VBS and compared them with those of CAS. METHODS: We enrolled patients who underwent VBS or CAS. Clinical variables and procedure-related factors were obtained. During the 3 years of follow-up, in-stent restenosis and infarction were investigated in each group. In-stent restenosis was defined as reduction in the lumen diameter > 50% compared with that after stenting. Factors associated with the occurrence of in-stent restenosis and stented-territory infarction in VBS and CAS were compared. RESULTS: Among 417 stent insertions (93 VBS and 324 CAS), there was no statistical difference in in-stent restenosis between VBS and CAS (12.9% vs. 6.8%, P = 0.092). However, stented-territory infarction was more frequently observed in VBS than in CAS (22.6% vs. 10.8%; P = 0.006), especially a month after stent insertion. HbA1c level, clopidogrel resistance, and multiple stents in VBS and young age in CAS increased the risk of in-stent restenosis. Diabetes (3.82 [1.24-11.7]) and multiple stents (22.4 [2.4-206.4]) were associated with stented-territory infarction in VBS. However, in-stent restenosis (odds ratio: 15.1, 95% confidence interval: 3.17-72.2) was associated with stented-territory infarction in CAS. CONCLUSIONS: Stented-territory infarction occurred more frequently in VBS, especially after the periprocedural period. In-stent restenosis was associated with stented-territory infarction after CAS, but not in VBS. The mechanism of stented-territory infarction after VBS may be different from that after CAS.

COVID-19 vaccine development based on recombinant viral and bacterial vector systems: combinatorial effect of adaptive and trained immunity.

Severe acute respiratory syndrome coronavirus 2 virus (SARS-CoV-2) infection, which causes coronavirus disease 2019 (COVID-19), has led to many cases and deaths worldwide. Therefore, a number of vaccine candidates have been developed to control the COVID-19 pandemic. Of these, to date, 21 vaccines have received emergency approval for human use in at least one country. However, the recent global emergence of SARS-CoV-2 variants has compromised the efficacy of the currently available vaccines. To protect against these variants, the use of vaccines that modulate T cell-mediated immune responses or innate immune cell memory function, termed trained immunity, is needed. The major advantage of a vaccine that uses bacteria or viral systems for the delivery of COVID-19 antigens is the ability to induce both T cell-mediated and humoral immune responses. In addition, such vaccine systems can also exert off-target effects via the vector itself, mediated partly through trained immunity; compared to other vaccine platforms, suggesting that this approach can provide better protection against even vaccine escape variants. This review presents the current status of the development of COVID-19 vaccines based on recombinant viral and bacterial delivery systems. We also discuss the current status of the use of licensed live vaccines for other infections, including BCG, oral polio and MMR vaccines, to prevent COVID-19 infections.

Recombinant Mycobacterium paragordonae Expressing SARS-CoV-2 Receptor-Binding Domain as a Vaccine Candidate Against SARS-CoV-2 Infections.

At present, concerns that the recent global emergence of SARS-CoV-2 variants could compromise the current vaccines have been raised, highlighting the urgent demand for new vaccines capable of eliciting T cell-mediated immune responses, as well as B cell-mediated neutralizing antibody production. In this study, we developed a novel recombinant Mycobacterium paragordonae expressing the SARS-CoV-2 receptor-binding domain (RBD) (rMpg-RBD-7) that is capable of eliciting RBD-specific immune responses in vaccinated mice. The potential use of rMpg-RBD-7 as a vaccine for SARS-CoV-2 infections was evaluated in in vivo using mouse models of two different modules, one for single-dose vaccination and the other for two-dose vaccination. In a single-dose vaccination model, we found that rMpg-RBD-7 versus a heat-killed strain could exert an enhanced cell-mediated immune (CMI) response, as well as a humoral immune response capable of neutralizing the RBD and ACE2 interaction. In a two-dose vaccination model, rMpg-RBD-7 in a two-dose vaccination could also exert a stronger CMI and humoral immune response to neutralize SARS-CoV-2 infections in pseudoviral or live virus infection systems, compared to single dose vaccinations of rMpg-RBD or two-dose RBD protein immunization. In conclusion, our data showed that rMpg-RBD-7 can lead to an enhanced CMI response and humoral immune responses in mice vaccinated with both single- or two-dose vaccination, highlighting its feasibility as a novel vaccine candidate for SARS-CoV-2. To the best of our knowledge, this study is the first in which mycobacteria is used as a delivery system for a SARS-CoV-2 vaccine.

A Hepatitis B Virus-Derived Peptide Can Inhibit Infection of Human Lung Cells with SARS-CoV-2 in a Type-1 Interferon-Dependent Manner.

The current COVID-19 pandemic has highlighted the urgent need to develop effective therapeutic strategies. We evaluated the in vitro antiviral effect against SARS-CoV-2 of a hepatitis B virus (HBV) hexamer peptide, Poly6, which is capable of eliciting an antiviral effect against human immunodeficiency virus -1 (HIV-1), as a novel HIV-1 integrase inhibitor, and a strong anticancer immune response in an IFN-I-dependent manner, as a novel potential adjuvant in anticancer immunotherapy. Here, we report that Poly6 exerts an anti-SARS-CoV-2 effect, with an estimated 50% inhibitory concentration of 2.617 µM, in the human bronchial epithelial cell line, Calu-3 but not in Vero-E6 cells, which are deficient in type 1 interferon (IFN-I) signaling. We proved via assays based on mRNA profiles, inhibitors, or blocking antibodies that Poly6 can exert an anti-SARS-CoV-2 effect in an IFN-I-dependent manner. We also found that Poly6 inhibits IL-6 production enhanced by SARS-CoV-2 in infected Calu-3 cells at both the transcription and the translation levels, mediated via IL-10 induction in an IFN-I-dependent manner. These results indicate the feasibility of Poly6 as an IFN-I-inducing COVID-19 drug with potent antiviral and anti-inflammatory activities.

A Novel DNA Vaccine Against SARS-CoV-2 Encoding a Chimeric Protein of Its Receptor-Binding Domain (RBD) Fused to the Amino-Terminal Region of Hepatitis B Virus preS1 With a W4P Mutation.

A coronavirus SARS-CoV-2, which has caused the pandemic viral pneumonia disease COVID-19, significantly threatens global public health, highlighting the need to develop effective and safe vaccines against its infection. In this study, we developed a novel DNA vaccine candidate against SARS-CoV-2 by expressing a chimeric protein of its receptor-binding domain (RBD) fused to a 33-bp sequence (11 aa) from the hepatitis B virus (HBV) preS1 region with a W4P mutation (W4P-RBD) at the N-terminal region and evaluated its immunogenicity. In vitro transfection experiments in multiple cell lines demonstrated that W4P-RBD vs. wild-type RBD protein (W-RBD) led to enhanced production of IL-6 and TNFα at the transcription and translation levels, suggesting the adjuvant potential of N-terminal HBV preS1 sequences for DNA vaccines against SARS-CoV-2. W4P-RBD also led to enhanced production of IgG and IgA, which can neutralize and block SARS-CoV-2 infection in both blood sera and bronchoalveolar lavage (BAL) fluid from the lung in vaccinated mice. Additionally, W4P-RBD led to an enhanced T-cell-mediated cellular immune response under S1 protein stimulation. In summary, W4P-RBD led to robust humoral and cell-mediated immune responses against SARS-CoV-2 in vaccinated mice, highlighting its feasibility as a novel DNA vaccine to protect against SARS-CoV-2 infection.