Analysis of the immunostimulatory effects of cytokine-expressing internal ribosome entry site-based RNA adjuvants and their applications.

Developing new adjuvants that can effectively induce both humoral and cellular immune responses while broadening the immune response is of great value. In this study, we aimed to develop GM-CSF- or IL-18-expressing single-stranded RNA (ssRNA) adjuvants based on the encephalomyocarditis virus (EMCV) internal ribosome entry site (IRES) and tested their efficacy in combination with ovalbumin (OVA) or inactivated influenza vaccines. Notably, cytokine-expressing RNA adjuvants increased the expression of antigen-presenting cell activation markers. Specifically, GM-CSF-expressing RNA adjuvants increased CD4+T cell responses, while IL-18-expressing RNA adjuvants increased CD8+T cell responses in mice when combined with OVA. In addition, cytokine-expressing RNA adjuvants increased the frequency of polyclonal T cells in combination with the influenza vaccine and reduced the clinical illness scores and weight loss of mice after viral challenge. Collectively, our results suggest that cytokine-expressing RNA adjuvants can be applied to protein-based or inactivated vaccines to increase their efficacy.

mRNA-HPV vaccine encoding E6 and E7 improves therapeutic potential for HPV-mediated cancers via subcutaneous immunization.

The E6 and E7 proteins of specific subtypes of human papillomavirus (HPV), including HPV 16 and 18, are highly associated with cervical cancer as they modulate cell cycle regulation. The aim of this study was to investigate the potential antitumor effects of a messenger RNA-HPV therapeutic vaccine (mHTV) containing nononcogenic E6 and E7 proteins. To achieve this, C57BL/6j mice were injected with the vaccine via both intramuscular and subcutaneous routes, and the resulting effects were evaluated. mHTV immunization markedly induced robust T cell-mediated immune responses and significantly suppressed tumor growth in both subcutaneous and orthotopic tumor-implanted mouse model, with a significant infiltration of immune cells into tumor tissues. Tumor retransplantation at day 62 postprimary vaccination completely halted progression in all mHTV-treated mice. Furthermore, tumor expansion was significantly reduced upon TC-1 transplantation 160 days after the last immunization. Immunization of rhesus monkeys with mHTV elicited promising immune responses. The immunogenicity of mHTV in nonhuman primates provides strong evidence for clinical application against HPV-related cancers in humans. All data suggest that mHTV can be used as both a therapeutic and prophylactic vaccine.

Adjuvant effect of IRES-based single-stranded RNA on melanoma immunotherapy.

BACKGROUND: Adjuvant therapies such as radiation therapy, chemotherapy, and immunotherapy are usually given after cancer surgery to improve the survival of cancer patients. However, despite advances in several adjuvant therapies, they are still limited in the prevention of recurrences. METHODS: We evaluated the immunological effects of RNA-based adjuvants in a murine melanoma model. Single-stranded RNA (ssRNA) were constructed based on the cricket paralysis virus (CrPV) internal ribosome entry site (IRES). Populations of immune cells in bone marrow cells and lymph node cells following immunization with CrPVIRES-ssRNA were determined using flow cytometry. Activated cytokine levels were measured using ELISA and ELISpot. The tumor protection efficacy of CrPVIRES-ssRNA was analyzed based on any reduction in tumor size or weight, and overall survival. RESULTS: CrPVIRES-ssRNA treatment stimulated antigen-presenting cells in the drain lymph nodes associated with activated antigen-specific dendritic cells. Next, we evaluated the expression of CD40, CD86, and XCR1, showing that immunization with CrPVIRES-ssRNA enhanced antigen presentation by CD8a+ conventional dendritic cell 1 (cDC1), as well as activated antigen-specific CD8 T cells. In addition, CrPVIRES-ssRNA treatment markedly increased the frequency of antigen-specific CD8 T cells and interferon-gamma (IFN-γ) producing cells, which promoted immune responses and reduced tumor burden in melanoma-bearing mice. CONCLUSIONS: This study provides evidence that the CrPVIRES-ssRNA adjuvant has potential for use in therapeutic cancer vaccines. Moreover, CrPVIRES-ssRNA possesses protective effects on various cancer cell models.

Single-stranded RNA adjuvant enhances the efficacy of 10-valent human papilloma virus-like particle vaccine.

Following the development of various types of vaccines, the use of adjuvants to boost vaccine efficacy has become a focus of research. Aluminum hydroxide (alum), the most commonly used adjuvant, induces a certain immune response and ensures safety in human trials. However, alum mainly induces only a Th2 response; its Th1 response is weak. Thus, we previously developed a single-stranded ribose nucleic acid (ssRNA) adjuvant that induces a Th1 response through toll-like receptors. Here, we explored whether 10-valent human papilloma virus (HPV)-like particle (VLP) vaccine formulated with ssRNA adjuvant and alum helped to enhance immune response and maintained memory response. The mice were immunized intramuscularly twice at 2 week intervals and were inoculated 4 days after the second boost (after about 1 year). The antibody response and T cell activation were measured by Elispot, ELISA using harvested serum and splenocytes. The 10-valent HPV VLP vaccine formulated with ssRNA adjuvant and alum increased the antigen-specific immune response more than alum used alone. It increased each type-specific IgG1/IgG2a titer, and antigen-specific IFN-γ cells. Furthermore, the ssRNA adjuvant with alum induced memory response. In memory response, each type-specific IgG1/IgG2c, IFN-γ, and IL-6 cytokine, and neutralizing antibodies were increased by the ssRNA adjuvant with alum. Overall, the ssRNA adjuvant with alum induced memory responses and balanced Th1/Th2 responses. The ssRNA adjuvant and alum may help to enhance prophylactic vaccine efficacy.

Comparison of 4 Different Cooldown Strategies on Lower-Leg Temperature, Blood Lactate Concentration, and Fatigue Perception After Intense Running.

CONTEXT: Although active recovery (AR) and cold application is recommended, many people take a shower after exercise. Therefore, a direct comparison between a shower and other recommended methods (AR and/or cold-water immersion) is necessary. To compare immediate effects of 4 postexercise cooldown strategies after running. DESIGN: A crossover design. METHODS: Seventeen young, healthy males (23 y; 174 cm; 73 kg) visited on 4 different days and performed a 10-minute intense treadmill run (5 km/h at a 1% incline, then a belt speed of 1 km/h, and an incline of 0.5% were increased every minute). Then, subjects randomly experienced 4 different 30-minute cooldown strategies each session-AR (10-min treadmill walk + 10-min static stretch + 10-min shower), cold-water walk (10-min shower + 20-min walk in cold water), cold-water sit (10-min shower + 20-min sit in cold water), and passive recovery (10-min shower + 20-min passive recovery). Across the cooldown conditions, the water temperatures for immersion and shower were set as 18 °C and 25 °C, respectively. Lower-leg muscle temperature, blood lactate concentration, and fatigue perception were statistically compared (P < .001 for all tests) and effect sizes (ES) were calculated. RESULTS: The cold-water walk condition (F135,2928 = 69.29, P < .0001) was the most effective in reducing muscle temperature after running (-11.6 °C, ES = 9.46, P < .0001), followed by the cold-water sit (-8.4 °C, ES = 8.61, P < .0001), passive recovery (-4.5 °C, ES = 4.36, P < .0001), and AR (-4.0 °C, ES = 4.29, P < .0001) conditions. Blood lactate concentration (F6,176 = 0.86, P = .52) and fatigue perception (F6,176 = 0.18, P = .98) did not differ among the 4 conditions. CONCLUSIONS: While the effect of lowering the lower-leg temperature was different, the effect of reducing blood lactate concentration and fatigue perception were similar in the 4 cooldown strategies. We suggest selecting the appropriate method while considering the specific goal, available time, facility, and accessibility.

Survival rates and risk factors for failure using an interposition vein graft for fingertip amputations with segmental vessel defects.

PURPOSE: This study aimed to compare survival rates and risk factors of replantation failures using an interposition vein graft in fingertip amputations with segmental vessel defects with those using simple end-to-end anastomosis in amputations. PATIENTS AND METHODS: Between 2004 and 2015, 776 (647 males and 129 females) with single Zone I or II amputations of digits underwent replantation. Among these, simple end-to-end anastomosis was performed in 698 replantations, while interposition vein grafts were used for either arterial or venous repair or both in 78 amputated fingertips. The survival rate was compared between the groups. Logistic regression analysis was performed to identify risk factors predicting replantation failure in all study subjects. RESULTS: Among 776 replantations, 713 (91.9%) survived. At latest follow-up, of 698 cases in the simple anastomosis group, 650 (93.1%) survived; of 78 cases in the vein graft group, 63 (80.8%) survived (p > .001). Logistic regression analysis revealed that avulsion type (odds ratio [OR] 3.121; 95% confidence interval [CI], 1.211-8.064; p = .018) and zone II amputation (OR, 2.370; 95% CI, 1.382-4.065; p = .002) were significant risk factors for replantation failure. CONCLUSION: This study demonstrates that the survival rate (80.8%) of the vein graft in fingertip amputation with segmental vessel defects was shown to be a possible option to increase the survival rates in case with segmental vessel defects where simple anastomosis could not be performed. However, avulsion type and zone II amputation are important risk factors of replantation failures.

Myoelectric Signal Classification of Targeted Muscles Using Dictionary Learning.

Surface electromyography (sEMG) signals comprise electrophysiological information related to muscle activity. As this signal is easy to record, it is utilized to control several myoelectric prostheses devices. Several studies have been conducted to process sEMG signals more efficiently. However, research on optimal algorithms and electrode placements for the processing of sEMG signals is still inconclusive. In addition, very few studies have focused on minimizing the number of electrodes. In this study, we investigated the most effective method for myoelectric signal classification with a small number of electrodes. A total of 23 subjects participated in the study, and the sEMG data of 14 different hand movements of the subjects were acquired from targeted muscles and untargeted muscles. Furthermore, the study compared the classification accuracy of the sEMG data using discriminative feature-oriented dictionary learning (DFDL) and other conventional classifiers. DFDL demonstrated the highest classification accuracy among the classifiers, and its higher quality performance became more apparent as the number of channels decreased. The targeted method was superior to the untargeted method, particularly when classifying sEMG signals with DFDL. Therefore, it was concluded that the combination of the targeted method and the DFDL algorithm could classify myoelectric signals more effectively with a minimal number of channels.

Sitting Posture Monitoring System Based on a Low-Cost Load Cell Using Machine Learning.

Sitting posture monitoring systems (SPMSs) help assess the posture of a seated person in real-time and improve sitting posture. To date, SPMS studies reported have required many sensors mounted on the backrest plate and seat plate of a chair. The present study, therefore, developed a system that measures a total of six sitting postures including the posture that applied a load to the backrest plate, with four load cells mounted only on the seat plate. Various machine learning algorithms were applied to the body weight ratio measured by the developed SPMS to identify the method that most accurately classified the actual sitting posture of the seated person. After classifying the sitting postures using several classifiers, average and maximum classification rates of 97.20% and 97.94%, respectively, were obtained from nine subjects with a support vector machine using the radial basis function kernel; the results obtained by this classifier showed a statistically significant difference from the results of multiple classifications using other classifiers. The proposed SPMS was able to classify six sitting postures including the posture with loading on the backrest and showed the possibility of classifying the sitting posture even though the number of sensors is reduced.

Intranasal immunization with the recombinant measles virus encoding the spike protein of SARS-CoV-2 confers protective immunity against COVID-19 in hamsters.

BACKGROUND: As the nasal mucosa is the initial site of infection for COVID-19, intranasal vaccines are more favorable than conventional vaccines. In recent clinical studies, intranasal immunization has been shown to generate higher neutralizing antibodies; however, there is a lack of evidence on sterilizing immunity in the upper airway. Previously, we developed a recombinant measles virus encoding the spike protein of SARS-CoV-2 (rMeV-S), eliciting humoral and cellular immune responses against SARS-CoV-2. OBJECTIVES: In this study, we aim to provide an experiment on nasal vaccines focusing on a measles virus platform as well as injection routes. STUDY DESIGN: Recombinant measles viruses expressing rMeV-S were prepared, and 5 × 105 PFUs of rMeV-S were administered to Syrian golden hamsters via intramuscular or intranasal injection. Subsequently, the hamsters were challenged with inoculations of 1 × 105 PFUs of SARS-CoV-2 and euthanized 4 days post-infection. Neutralizing antibodies and RBD-specific IgG in the serum and RBD-specific IgA in the bronchoalveolar lavage fluid (BALF) were measured, and SARS-CoV-2 clearance capacity was determined via quantitative reverse-transcription PCR (qRT-PCR) analysis and viral titer measurement in the upper respiratory tract and lungs. Immunohistochemistry and histopathological examinations of lung samples from experimental hamsters were conducted. RESULTS: The intranasal immunization of rMeV-S elicits protective immune responses and alleviates virus-induced pathophysiology, such as body weight reduction and lung weight increase in hamsters. Furthermore, lung immunohistochemistry demonstrated that intranasal rMeV-S immunization induces effective SARS-CoV-2 clearance that correlates with viral RNA content, as determined by qRT-PCR, in the lung and nasal wash samples, SARS-CoV-2 viral titers in lung, nasal wash, BALF samples, serum RBD-specific IgG concentration, and RBD-specific IgA concentration in the BALF. CONCLUSION: An intranasal vaccine based on the measles virus platform is a promising strategy owing to the typical route of infection of the virus, the ease of administration of the vaccine, and the strong immune response it elicits.

Multiclass classification of imagined speech EEG using noise-assisted multivariate empirical mode decomposition and multireceptive field convolutional neural network.

Introduction: In this study, we classified electroencephalography (EEG) data of imagined speech using signal decomposition and multireceptive convolutional neural network. The imagined speech EEG with five vowels /a/, /e/, /i/, /o/, and /u/, and mute (rest) sounds were obtained from ten study participants. Materials and methods: First, two different signal decomposition methods were applied for comparison: noise-assisted multivariate empirical mode decomposition and wavelet packet decomposition. Six statistical features were calculated from the decomposed eight sub-frequency bands EEG. Next, all features obtained from each channel of the trial were vectorized and used as the input vector of classifiers. Lastly, EEG was classified using multireceptive field convolutional neural network and several other classifiers for comparison. Results: We achieved an average classification rate of 73.09 and up to 80.41% in a multiclass (six classes) setup (Chance: 16.67%). In comparison with various other classifiers, significant improvements for other classifiers were achieved (p-value < 0.05). From the frequency sub-band analysis, high-frequency band regions and the lowest-frequency band region contain more information about imagined vowel EEG data. The misclassification and classification rate of each vowel imaginary EEG was analyzed through a confusion matrix. Discussion: Imagined speech EEG can be classified successfully using the proposed signal decomposition method and a convolutional neural network. The proposed classification method for imagined speech EEG can contribute to developing a practical imagined speech-based brain-computer interfaces system.

mRNA vaccine encoding Gn provides protection against severe fever with thrombocytopenia syndrome virus in mice.

We developed a promising mRNA vaccine against severe fever with thrombocytopenia syndrome (SFTS), an infectious disease caused by the SFTS virus that is primarily transmitted through tick bites. Administration of lipid nanoparticle-encapsulated mRNA-Gn successfully induced neutralizing antibodies and T-cell responses in mice. The vaccinated mice were protected against a lethal SFTS virus challenge, suggesting that this mRNA vaccine may be an effective and successful SFTS vaccine candidate.

Analyzing immune responses to varied mRNA and protein vaccine sequences.

In response to the COVID-19 pandemic, different types of vaccines, such as inactive, live-attenuated, messenger RNA (mRNA), and protein subunit, have been developed against SARS-CoV-2. This has unintentionally created a unique scenario where heterologous prime-boost vaccination against a single virus has been administered to a large human population. Here, we aimed to analyze whether the immunization order of vaccine types influences the efficacy of heterologous prime-boost vaccination, especially mRNA and protein-based vaccines. We developed a new mRNA vaccine encoding the hemagglutinin (HA) glycoprotein of the influenza virus using the 3'-UTR and 5'-UTR of muscle cells (mRNA-HA) and tested its efficacy by heterologous immunization with an HA protein vaccine (protein-HA). The results demonstrated higher IgG2a levels and hemagglutination inhibition titers in the mRNA-HA priming/protein-HA boosting (R-P) regimen than those induced by reverse immunization (protein-HA priming/mRNA-HA boosting, P-R). After the viral challenge, the R-P group showed lower virus loads and less inflammation in the lungs than the P-R group did. Transcriptome analysis revealed that the heterologous prime-boost groups had differentially activated immune response pathways, according to the order of immunization. In summary, our results demonstrate that the sequence of vaccination is critical to direct desired immune responses. This study demonstrates the potential of a heterologous vaccination strategy using mRNA and protein vaccine platforms against viral infection.

Recombinant measles virus encoding the spike protein of SARS-CoV-2 efficiently induces Th1 responses and neutralizing antibodies that block SARS-CoV-2 variants.

Owing to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants, the development of effective and safe vaccines has become a priority. The measles virus (MeV) vaccine is an attractive vaccine platform as it has been administered to children for more than 40 years in over 100 countries. In this study, we developed a recombinant MeV expressing the full-length SARS-CoV-2 spike protein (rMeV-S) and tested its efficacy using mouse and hamster models. In hCD46Tg mice, two-dose rMeV-S vaccination induced higher Th1 secretion and humoral responses than one-dose vaccination. Interestingly, neutralizing antibodies induced by one-dose and two-dose rMeV-S immunization effectively blocked the entry of the α, ß, γ, and δ variants of SARS-CoV-2. Furthermore, two-dose rMeV-S immunization provided complete protection against SARS-CoV-2 in the hamster model. These results suggest the potential of rMeV-S as a vaccine candidate for targeting SARS-CoV-2 and its variants.

Heterologous vaccination utilizing viral vector and protein platforms confers complete protection against SFTSV.

Severe fever with thrombocytopenia syndrome virus was first discovered in 2009 as the causative agent of severe fever with thrombocytopenia syndrome. Despite its potential threat to public health, no prophylactic vaccine is yet available. This study developed a heterologous prime-boost strategy comprising priming with recombinant replication-deficient human adenovirus type 5 (rAd5) expressing the surface glycoprotein, Gn, and boosting with Gn protein. This vaccination regimen induced balanced Th1/Th2 immune responses and resulted in potent humoral and T cell-mediated responses in mice. It elicited high neutralizing antibody titers in both mice and non-human primates. Transcriptome analysis revealed that rAd5 and Gn proteins induced adaptive and innate immune pathways, respectively. This study provides immunological and mechanistic insight into this heterologous regimen and paves the way for future strategies against emerging infectious diseases.

Spontaneous Recovery of Traumatic Unilateral Superior Oblique Palsy and Ocular Factors for Predicting Prognosis.

PURPOSE: This study evaluated the prognosis of patients with traumatic unilateral superior oblique palsy (SOP) and clinical factors associated with spontaneous resolution. METHODS: Medical records of patients with traumatic unilateral SOP who visited two hospitals (Yeungnam University Hospital and Daegu Catholic University Medical Center) between January 2015 and June 2020 were reviewed retrospectively. When traumatic unilateral SOP did not recover within at least 1 year of follow-up, no spontaneous resolution was considered. Both traumatic and ocular factors were evaluated to evaluate their association with spontaneous recovery. RESULTS: Fifty-nine patients (mean age, 52.6 years; 48 male patients) were enrolled in this study. The mean interval from trauma to initial presentation was 3.9 months. The mean vertical deviation at initial presentation was 6.34 ± 5.22 prism diopters (PD) (range, 0-25 PD). During the mean 24.1-month follow-up period, 28 patients (47.5%) achieved spontaneous resolution of SOP. Thirteen patients underwent surgical treatment for SOP. Vertical deviation <6 PD at the initial visit and low fundus torsion in the nonparetic eye and both eyes were significantly associated with spontaneous recovery (p < 0.05, logistic regression analysis). Traumatic factors, including the trauma type, presence of intracranial lesion, loss of consciousness, and Glasgow Coma Scale score, were not associated with spontaneous recovery. CONCLUSIONS: In this multicenter study, spontaneously recovery was achieved in 47.5% patients with traumatic unilateral SOP. Even mild head trauma can lead to permanent SOP. Ocular factors, including the angle of deviation and fundus torsion, may better predict spontaneous resolution than traumatic factors in patients with traumatic unilateral SOP.

Postoperative immobilization using a short-arm cast in the semisupination position is appropriate after arthroscopic triangular fibrocartilage complex foveal repair.

AIMS: The aim of this study was to assess and compare active rotation of the forearm in normal subjects after the application of a short-arm cast (SAC) in the semisupination position and a long-arm cast (LAC) in the neutral position. A clinical study was also conducted to compare the functional outcomes of using a SAC in the semisupination position with those of using a LAC in the neutral position in patients who underwent arthroscopic triangular fibrocartilage complex (TFCC) foveal repair. METHODS: A total of 40 healthy right-handed volunteers were recruited. Active pronation and supination of the forearm were measured in each subject using a goniometer. In the retrospective clinical study, 40 patients who underwent arthroscopic foveal repair were included. The wrist was immobilized postoperatively using a SAC in the semisupination position (approximately 45°) in 16 patients and a LAC in 24. Clinical outcomes were assessed using grip strength and patient-reported outcomes. The degree of disability caused by cast immobilization was also evaluated when the cast was removed. RESULTS: Supination was significantly more restricted with LACs than with SACs in the semisupination position in male and female patients (p < 0.001 for both). However, pronation was significantly more restricted with SACs in the semisupination position than with LACs in female patients (p = 0.003) and was not significantly different in male patients (p = 0.090). In the clinical study, both groups showed improvement in all parameters with significant differences in grip strength, visual analogue scale scores for pain, modified Mayo Wrist Score, the Disability of the Arm, Shoulder, and Hand (DASH) score, and the Patient-Rated Wrist Evaluation (PRWE) score. No significant postoperative differences were noted between LACs and SACs in the semisupination position. However, the disability caused by immobilization in a cast was significantly higher in patients who had a LAC on the dominant hand (p < 0.001). CONCLUSION: We found that a SAC in the semisupination position is as effective as a LAC in restricting pronation of the forearm. In addition, postoperative immobilization with a SAC in the semisupination position resulted in comparable pain scores and functional outcomes to immobilization with a LAC after TFCC foveal repair, with less restriction of daily activities. Therefore, we recommend that surgeons consider using a SAC in the semisupination position for postoperative immobilization following TFCC foveal repair for dorsal instability of the distal radioulnar joint. Cite this article: Bone Joint J 2022;104-B(2):249-256.

Neutralizing Antibodies to Severe Fever With Thrombocytopenia Syndrome Virus Among Survivors, Non-Survivors and Healthy Residents in South Korea.

Severe fever with thrombocytopenia syndrome (SFTS), a newly emerging tick-borne viral disease, has been detected in Asia since 2009, and person-to-person transmission is possible. SFTS is characterized by atypical signs, including mild to severe febrile illness similar to that associated with hemorrhagic fever, with 16.2 to 30% mortality. We found that the titers of neutralizing antibodies, play an important role in protective immunity, to SFTS virus (SFTSV) in survivors and healthy residents who lived in endemic areas and who were positive for SFTSV IgG, were higher than those in non-survivor patients. Moreover, the titers were maintained in surviving patients and healthy residents but not in non-surviving patients in South Korea.

Effective inactivated influenza vaccine for the elderly using a single-stranded RNA-based adjuvant.

There is an unmet need for new influenza vaccine strategies that compensate for impaired vaccine responses in elderly individuals. Here, we evaluated the effectiveness of a single-stranded RNA (ssRNA) as an adjuvant to enhance the efficacy of inactivated influenza vaccine (IIV) in mouse models. Immunization with the ssRNA along with IIV reduced viral titers as well as pathological and inflammatory scores in the lungs after influenza challenge in aged mice. ssRNA induced balanced Th1/Th2 responses with an increase in IgA titers. Moreover, the ssRNA adjuvant markedly increased the frequency of influenza HA-specific T cells and IFN-γ production along with the expression of genes related to innate and adaptive immune systems that could overcome immunosenescence in aged mice. Our findings indicate that ssRNA is an efficient vaccine adjuvant that boosts cellular and humoral immunity in aged mice, demonstrating its potential as a novel adjuvant for currently available influenza virus vaccines for elderly individuals.

Immunization with RBD-P2 and N protects against SARS-CoV-2 in nonhuman primates.

Since the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), various vaccines are being developed, with most vaccine candidates focusing on the viral spike protein. Here, we developed a previously unknown subunit vaccine comprising the receptor binding domain (RBD) of the spike protein fused with the tetanus toxoid epitope P2 (RBD-P2) and tested its efficacy in rodents and nonhuman primates (NHPs). We also investigated whether the SARS-CoV-2 nucleocapsid protein (N) could increase vaccine efficacy. Immunization with N and RBD-P2 (RBDP2/N) + alum increased T cell responses in mice and neutralizing antibody levels in rats compared with those obtained using RBD-P2 + alum. Furthermore, in NHPs, RBD-P2/N + alum induced slightly faster SARS-CoV-2 clearance than that induced by RBD-P2 + alum, albeit without statistical significance. Our study supports further development of RBD-P2 as a vaccine candidate against SARS-CoV-2. Also, it provides insights regarding the use of N in protein-based vaccines against SARS-CoV-2.

Comparison of Bone Preservation in Elderly Patients with Femoral Neck Fracture After Bipolar Hemiarthroplasty Using Shorter Femoral Stem and Standard Femoral Stem.

BACKGROUND: This randomized control study was designed to compare the clinical and radiological outcomes, including periprosthetic bone mineral density (BMD) changes, between the short and standard stems after using cementless hemiarthroplasty in elderly patients with femur neck fractures. MATERIALS AND METHODS: From January 2013 to May 2017, 151 patients (aged ≥ 65 years) underwent hemiarthroplasties due to femoral neck fractures. Patients were randomized into two groups; 77 patients in Group A implanting the short femoral stem and 74 patients in Group B implanting the standard femoral stem. Clinical and radiographic evaluations were performed in all patients. RESULTS: 75 patients (40 patients in Group A and 35 patients in Group B) completed routine follow-up for a minimum of 2 years. The clinical outcomes, including ambulatory functions and thigh pain, were similar in both groups. All the femoral stems acquired radiologic stability. At postoperative one year, BMD values in Gruen zone (G) seven on the standard stem side were significantly lower than those on the short stem side (P = 0.038). At the second year of follow-up, the BMD values of Group A in G1, G3, G4, and G7 were significantly greater than those of Group B (P = 0.007, 0.032, 0.026, and P < 0.000, respectively). CONCLUSIONS: Both the clinical outcomes and radiologic stability in both group demonstrated similar results in elderly patients with femoral neck fracture at the latest follow-up. In addition, the periprosthetic BMD of the short femoral stems demonstrated better periprosthetic bone preservation at a minimum of 2 years of follow-up. LEVEL OF EVIDENCES: Therapeutic Level II.