Lipid Nanoparticle with 1,2-Di-O-octadecenyl-3-trimethylammonium-propane as a Component Lipid Confers Potent Responses of Th1 Cells and Antibody against Vaccine Antigen.

Adjuvants are effective tools to enhance vaccine efficacy and control the type of immune responses such as antibody and T helper 1 (Th1)- or Th2-type responses. Several studies suggest that interferon (IFN)-γ-producing Th1 cells play a significant role against infections caused by intracellular bacteria and viruses; however, only a few adjuvants can induce a strong Th1-type immune response. Recently, several studies have shown that lipid nanoparticles (LNPs) can be used as vaccine adjuvants and that each LNP has a different adjuvant activity. In this study, we screened LNPs to develop an adjuvant that can induce Th1 cells and antibodies using a conventional influenza split vaccine (SV) as an antigen in mice. We observed that LNP with 1,2-di-O-octadecenyl-3-trimethylammonium-propane (DOTMA) as a component lipid (DOTMA-LNP) elicited robust SV-specific IgG1 and IgG2 responses compared with SV alone in mice and was as efficient as SV adjuvanted with other adjuvants in mice. Furthermore, DOTMA-LNPs induced robust IFN-γ-producing Th1 cells without inflammatory responses compared to those of other adjuvants, which conferred strong cross-protection in mice. We also demonstrated the high versatility of DOTMA-LNP as a Th1 cell-inducing vaccine adjuvant using vaccine antigens derived from severe acute respiratory syndrome coronavirus 2 and Streptococcus pneumoniae. Our findings suggest the potential of DOTMA-LNP as a safe and effective Th1 cell-inducing adjuvant and show that LNP formulations are potentially potent adjuvants to enhance the effectiveness of other subunit vaccines.

Isolated cortical vein thrombosis with hemorrhagic infarction during the application of a transdermal estradiol patch: A case report.

Isolated cortical vein thrombosis (ICVT) is a rarer subtype of cerebral venous sinus thrombosis (CVST) that involves only the cortical veins without any thrombosis in the major cerebral veins or sinuses. Among the known causes of CVST are factors, such as being a young female or the use of hormonal preparations. This study presents a case of a 35-year-old female who underwent endometrial polyp removal 5 days before symptom onset and started using a transdermal estradiol patch. After 4 days of using the transdermal estradiol patch, the patient developed recurrent seizures and sustained sensory aphasia. The head computed tomography revealed hemorrhagic infarction. Given her young age and the use of hormonal therapy, CVST was suspected. However, the initial diagnosis with magnetic resonance imaging (MRI) was inconclusive, and no venous sinus thrombosis could be identified on additional cerebral angiography. Instead, stasis of venous flow in the temporal vein was noted. It was difficult to determine whether these findings were due to hemorrhage or ICVT. Upon re-evaluation with MRI, signal changes suggestive of thrombosis in a cortical vein in the parietal region, which is different from the stasis observed in cerebral angiography, led to the diagnosis of ICVT. This is the first study to link the use of transdermal estradiol patches to ICVT. In cases where ICVT leads to cerebral hemorrhage, cerebral angiography may not be useful. Instead, a comprehensive diagnosis should be made based on imaging findings from various MRI sequences and the patient's medical history.

Adjuvant-free parenterally injectable vaccine platform that harnesses previously induced IgG as an antigen delivery carrier.

Subunit vaccines are among the most useful vaccine modalities; however, their low immunogenicity necessitates the addition of adjuvants. Although adjuvants improve immune responses induced by vaccines, they often cause adverse reactions. To address this, we developed an adjuvant-free subunit vaccine platform that uses pre-existing antibodies generated from past infections or vaccinations as carriers for the delivery of vaccine antigens. Although we have confirmed the usefulness of this platform for nasal vaccines, its suitability as a parenterally injectable vaccine remains uncertain. Here, we verified the potential of our vaccine platform to harness pre-existing immunity for parenterally injectable vaccines. We generated RBD-HA by combining the receptor binding domain (RBD) derived from SARS-CoV-2 as a vaccine antigen with hemagglutinin (HA) sourced from influenza viruses to serve as the carrier protein. We revealed that subcutaneous vaccination with RBD-HA effectively triggered strong RBD-specific IgG responses in mice previously infected with the influenza A virus, even in the absence of adjuvants, and conferred protection to mice against SARS-CoV-2 upon challenge. Furthermore, we revealed that vaccination with RBD-HA did not induce an inflammatory response, such as inflammatory cytokine production, swelling, and recruitment of inflammatory immune cells, whereas conventional vaccines combined with adjuvants induced these adverse reactions. In addition, we demonstrated the remarkable versatility of this platform using a vaccine antigen derived from Streptococcus pneumoniae. These findings indicate the potential of this adjuvant-free vaccine platform to enhance the efficacy of parenterally injectable subunit vaccines and reduce adverse reactions.

Mechanical Thrombectomy Using Double Stent Retriever Technique for Acute Ischemic Stroke Following Embolism From the Pulmonary Vein Stump After Left Upper Lobectomy: A Case Report.

Acute ischemic stroke (AIS) following pulmonary lobectomy, which is traditionally attributed to air embolism and atrial fibrillation (AF), may occur after thrombus formation in the pulmonary vein stump (PVS). Herein, we document the mechanical thrombectomy (MT) of a carotid bifurcation occlusion post-left upper lobectomy (LUL) to manage AIS. A 76-year-old male with a history of diabetes, dyslipidemia, and a treated dural arteriovenous fistula at the transverse sigmoid junction, with no history of AF, successfully underwent LUL for a pulmonary tumor. The patient independently walked on postoperative day 1. He developed right hemiparesis and total aphasia on the morning of the second day after surgery, which was discovered by the nursing staff. A magnetic resonance imaging (MRI) confirmed an occlusion of the left common carotid artery (CCA). Tissue plasminogen activator (t-PA) was not administered owing to recent surgery. An urgent MT using multiple MT techniques carried out 90 minutes after the discovery of symptoms only achieved partial recanalization. Subsequently, a double stent retriever technique (DSRT) addressed the occlusion in the common and cervical internal carotid artery (ICA). Following this, a T occlusion was encountered, which was addressed with a combined approach using a single stent retriever (SR), achieving a thrombolysis in cerebral infarction (TICI) grade 2b result. However, postoperative aphasia and severe right hemiparesis remained. Postoperative imaging showed a significant left cerebral hemisphere infarction and a thrombus in the PVS. Oral edoxaban was administered, and PVS thrombosis did not recur. The patient was transferred to a rehabilitation facility 190 days post-embolization with a modified Rankin Scale score of 4. In this report, we demonstrate the challenging case of the DSRT in addressing AIS after LUL, which led to the formation of a massive thrombus and occlusion of the carotid artery, as revealed by the PVS. This case emphasizes the importance of collaborative efforts between thoracic surgeons and all staff involved in stroke care in managing such complex scenarios.