Potent Serum Research Articles

Cross-reactive antibody response to Monkeypox virus surface proteins in a small proportion of individuals with and without Chinese smallpox vaccination history

BackgroundAfter the eradication of smallpox in China in 1979, vaccination with the vaccinia virus (VACV) Tiantan strain for the general population was stopped in 1980. As the monkeypox virus (MPXV) is rapidly spreading in the world, we would like to investigate whether the individuals with historic VACV Tiantan strain vaccination, even after more than 40 years, could still provide ELISA reactivity and neutralizing protection; and whether the unvaccinated individuals have no antibody reactivity against MPXV at all.ResultsWe established serologic ELISA to measure the serum anti-MPXV titer by using immunodominant MPXV surface proteins, A35R, B6R, A29L, and M1R. A small proportion of individuals (born before 1980) with historic VACV Tiantan strain vaccination exhibited serum ELISA cross-reactivity against these MPXV surface proteins. Consistently, these donors also showed ELISA seropositivity and serum neutralization against VACV Tiantan strain. However, surprisingly, some unvaccinated young adults (born after 1980) also showed potent serum ELISA activity against MPXV proteins, possibly due to their past infection by some self-limiting Orthopoxvirus (OPXV).ConclusionsWe report the serum ELISA cross-reactivity against MPXV surface protein in a small proportion of individuals both with and without VACV Tiantan strain vaccination history. Combined with our serum neutralization assay against VACV and the recent literature about mice vaccinated with VACV Tiantan strain, our study confirmed the anti-MPXV cross-reactivity and cross-neutralization of smallpox vaccine using VACV Tiantan strain. Therefore, it is necessary to restart the smallpox vaccination program in high risk populations.

Tetrahedral Framework Nucleic Acids Based Small Interfering RNA Targeting Receptor for Advanced Glycation End Products for Diabetic Complications Treatment.

Complications arising from diabetes can threaten multiple organs. Advanced glycation end products (AGEs) play a significant role in inducing these complications. Highly processed diets and hyperglycemia facilitate the accumulation of AGEs in the body. Interaction between AGEs and their main receptor (RAGE) initiates the transmission of intracellular inflammatory and cell death signals, which ultimately lead to complications. To counter AGEs-induced damage, we developed an siRNA-binding tetrahedral framework nucleic acids (TDN) system, termed Tsi, which combines the potent cell membrane penetrability and serum stability of TDN with the gene-targeting specificity of siRNA-RAGE. Tsi effectively and persistently downregulates the expression of RAGE, thereby suppressing inflammation by blocking the NF-κB pathway as well as exhibiting antioxidant functions. Furthermore, Tsi regulates the pyroptosis state of macrophages via the NLRP3/caspase-1 axis, which inhibits the spread of cell death signals and maintains homeostasis. This is of great significance for the synergistic treatment strategy for systemic complications in patients with refractory hyperglycemia. In summary, this study describes a nanomedicine that targets the RAGE and suppresses AGE-induced inflammation. This nucleic acid drug holds long-lasting efficacy and is independent of lowering hyperglycemia, which provides a strategy for the treatment of diabetic complications and age-related diseases.

Comparative investigation on interaction between potent antimalarials and human serum albumin using multispectroscopic and computational approaches.

This study performed a comparative investigation to explore the interaction mechanisms between two potential antimalarial compounds, JMI 346 and JMI 105, and human serum albumin (HSA), a vital carrier protein responsible for maintaining important biological functions. Our aim was to assess the pharmacological efficiency of these compounds while comprehensively analyzing their impact on the dynamic behavior and overall stability of the protein. A comprehensive array of multispectroscopic techniques, including UV-Vis. spectroscopy, steady-state fluorescence analysis, synchronous fluorescence spectroscopy, three-dimensional fluorescence and circular dichroism spectroscopy, docking studies, and molecular dynamics simulations, were performed to probe the intricate details of the interaction between the compounds and HSA. Our results revealed that both JMI 346 and JMI 105 exhibited promising pharmacological effectiveness within the context of malaria therapy. However, JMI 346 was found to exhibit a significantly higher affinity and only minor altered impact on HSA, suggesting a more favorable interaction with the protein on the dynamic behavior and overall stability of the protein in comparison to JMI 105. Further studies can build on these results to optimize the drug-protein interaction and enable the development of more potent and targeted antimalarial treatments.

Biosynthesis and Immunological Evaluation of a Dual-Antigen Nanoconjugate Vaccine Against Brucella melitensis

Brucellosis, caused by Brucella, is one of the most common zoonosis. However, there is still no vaccine for human use. Although some live attenuated vaccines have been approved for animals, the protection effect is not ideal. In this study, we developed a dual-antigen nanoconjugate vaccine containing both polysaccharide and protein antigens against Brucella. First, the antigenic polysaccharide was covalently coupled to the outer membrane protein Omp19 using protein glycan coupling technology, and then it was successfully loaded on a nano-carrier through the SpyTag/SpyCatcher system. After confirming the efficient immune activation and safety performance of the dual-antigen nanoconjugate vaccine, the potent serum antibody response against the two antigens and remarkable protective effect in non-lethal and lethal Brucella infection models were further demonstrated through different routes of administration. These results indicated that the dual-antigen nanoconjugate vaccine enhanced both T helper 1 cell (Th1) and Th2 immune responses and protected mice from Brucella infection. Furthermore, we found that this protective effect was maintained for at least 18 weeks. To our knowledge, this is the first Brucella vaccine bearing diverse antigens, including a protein and polysaccharide, on a single nanoparticle. Thus, we also present an attractive technology for co-delivery of different types of antigens using a strategy applicable to other vaccines against infectious diseases.

The pH-responsive zeolitic imidazolate framework nanoparticle as a promising immune-enhancing adjuvant for anti-caries vaccine

ObjectivesStreptococcus mutans (S. mutans) is the main aetiologic bacterium of dental caries, whose protein antigen (PAc) has been administered as an anti-caries vaccine. In addition, several fusion proteins or PAc combined with adjuvants were used as anti-caries vaccines to improve the relatively weak immunogenicity of PAc. However, there are no nanoparticle-based adjuvants with good biocompatibility, excellent biodegradability, or the high loading performance of antigens used for anti-caries vaccines. This study aimed to prepare an innovative nanoparticle-based anti-caries vaccine and evaluate immune responses elicited by this vaccine in vitro and in vivo. MethodsIn this study, an anti-caries vaccine was prepared by an antigen of recombinant protein PAc from S. mutans and an adjuvant of zeolitic imidazolate framework-8 nanoparticles (ZIF-8 NPs) synthesized using a hydrothermal method. Then, mice were administrated intranasally by ZIF-8@PAc vaccine, and immune responses were evaluated. ResultsZIF-8 NPs not only greatly improved the internalization of the antigen but also released the PAc protein after degradation of ZIF-8 NPs in lysosomes for the further processing and presentation of antigen-presenting cells. In addition, ZIF-8@PAc induced significantly more potent PAc-specific serum IgG and saliva IgA antibodies, a higher splenocyte proliferation index, higher levels of the cytokines IL-4, IL-6, IL-10, IL-17A and IFN-γ, and a higher percentage of mature DCs and CD4+ memory T cells in vivo. ConclusionsThe ZIF-8 NPs, as an anti-caries vaccine adjuvant-assisted antigen PAc, elicit significantly potent immune responses, aiding in the further prevention of dental caries. Clinical significanceVaccine immunotherapy is an attractive strategy for prevention and treatment of dental caries. The ZIF-8@PAc vaccine can induce significantly high level of immune responses in this study, which indicates great potential for prevention and treatment of caries.

Complementary antibody lineages achieve neutralization breadth in an HIV-1 infected elite neutralizer.

Broadly neutralizing antibodies (bNAbs) have remarkable breadth and potency against most HIV-1 subtypes and are able to prevent HIV-1 infection in animal models. However, bNAbs are extremely difficult to induce by vaccination. Defining the developmental pathways towards neutralization breadth can assist in the design of strategies to elicit protective bNAb responses by vaccination. Here, HIV-1 envelope glycoproteins (Env)-specific IgG+ B cells were isolated at various time points post infection from an HIV-1 infected elite neutralizer to obtain monoclonal antibodies (mAbs). Multiple antibody lineages were isolated targeting distinct epitopes on Env, including the gp120-gp41 interface, CD4-binding site, silent face and V3 region. The mAbs each neutralized a diverse set of HIV-1 strains from different clades indicating that the patient's remarkable serum breadth and potency might have been the result of a polyclonal mixture rather than a single bNAb lineage. High-resolution cryo-electron microscopy structures of the neutralizing mAbs (NAbs) in complex with an Env trimer generated from the same individual revealed that the NAbs used multiple strategies to neutralize the virus; blocking the receptor binding site, binding to HIV-1 Env N-linked glycans, and disassembly of the trimer. These results show that diverse NAbs can complement each other to achieve a broad and potent neutralizing serum response in HIV-1 infected individuals. Hence, the induction of combinations of moderately broad NAbs might be a viable vaccine strategy to protect against a wide range of circulating HIV-1 viruses.

Broadly neutralizing antibodies to SARS-related viruses can be readily induced in rhesus macaques.

To prepare for future coronavirus (CoV) pandemics, it is desirable to generate vaccines capable of eliciting broadly neutralizing antibody responses to CoVs. Here, we show that immunization of macaques with SARS-CoV-2 spike (S) protein with a two-shot protocol generated potent serum receptor binding domain cross-neutralizing antibody responses to both SARS-CoV-2 and SARS-CoV-1. Furthermore, responses were equally effective against most SARS-CoV-2 variants of concern (VOCs) and some were highly effective against Omicron. This result contrasts with human infection or many two-shot vaccination protocols where responses were typically more SARS-CoV-2 specific and where VOCs were less well neutralized. Structural studies showed that cloned macaque neutralizing antibodies, particularly using a given heavy chain germline gene, recognized a relatively conserved region proximal to the angiotensin converting enzyme 2 receptor binding site (RBS), whereas many frequently elicited human neutralizing antibodies targeted more variable epitopes overlapping the RBS. B cell repertoire differences between humans and macaques appeared to influence the vaccine response. The macaque neutralizing antibodies identified a pan-SARS-related virus epitope region less well targeted by human antibodies that could be exploited in rational vaccine design.

SARS-CoV-2 Spike Stem Protein Nanoparticles Elicited Broad ADCC and Robust Neutralization against Variants in Mice.

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has caused the global pandemic. The virus is rapidly evolving, characterized by the emergence of several major variants. Stable prefusion spike protein (Pre) is the immunogen in current vaccines but is limited in protecting against different variants. Here, the immune responses induced by the relatively conserved stem subunit (S2) of spike protein versus Pre are investigated. Pre generates the most robust neutralization responses against SARS‐CoV‐2 variants in vesicular stomatitis virus pseudovirus‐based assessment but elicits less antibody‐dependent cellular cytotoxicity (ADCC) activity than S2. By contrast, S2 induces the most balanced immunoglobulin G (IgG) antibodies with potent and broad ADCC activity although produces weaker neutralization. The immunogenicity of S2 and Pre improves by incorporating the two proteins into double‐layered protein nanoparticles. The resulting protein nanoparticles Pre/S2 elicit higher neutralizing antibodies than Pre alone, and stronger ADCC than S2 alone. Moreover, nanoparticles produce more potent and balanced serum IgG antibodies than the corresponding soluble protein mixture, and the immune responses are sustained for at least four months after the immunization. Thus, the double‐layered protein nanoparticles have the potential to be developed into broader SARS‐CoV‐2 vaccines with excellent safety profiles.

Pre-clinical assessment of SLN360, a novel siRNA targeting LPA, developed to address elevated lipoprotein (a) in cardiovascular disease

Background and aimsThe LPA gene encodes apolipoprotein (a), a key component of Lp(a), a potent risk factor for cardiovascular disease with no specific pharmacotherapy. Here we describe the pharmacological data for SLN360, a GalNAc-conjugated siRNA targeting LPA, designed to address this unmet medical need. MethodsSLN360 was tested in vitro for LPA knockdown in primary hepatocytes. Healthy cynomolgus monkeys received single or multiple subcutaneous doses of the SLN360 sequence ranging from 0.1 to 9.0 mg/kg to determine the pharmacokinetic and pharmacodynamic effects. Liver mRNA and serum biomarker analyses were performed. ResultsIn vitro, the SLN360 sequence potently reduces LPA mRNA in primary cynomolgus and human hepatocytes, while no effect was observed on the expression of APOB or PLG. In vivo, SLN360 exposure peaks 2 h after subcutaneous injection with near full elimination by 24 h. Specific LPA mRNA reduction (up to 91% 2 weeks after dosing) was observed with only the 3 mg/kg group showing appreciable return to baseline (40%). No consistent dose- or time-dependent effect on the expression of APOB, PLG or a panel of sensitive markers of liver lipid accumulation was observed. Potent (up to 95%) and long lasting (≥9 weeks) serum Lp(a) reduction was observed, peaking in all active groups at day 21. The minimally effective dose was determined to be 0.3 mg/kg with an ED50 of 0.6 mg/kg. ConclusionsSLN360 induces a sustained reduction in serum Lp(a) levels in cynomolgus monkeys following subcutaneous dosing. SLN360 has potential to address the unmet need of Lp(a) reduction in cardiovascular diseases.

Interplay of infection and vaccination in long-term protection from COVID-19

Interplay of infection and vaccination in long-term protection from COVID-19

Rapid biosensing SARS-CoV-2 antibodies in vaccinated healthy donors

In this study, we report two fiber optic-biolayer interferometry (FO-BLI)-based biosensors for the rapid detection of SARS-CoV-2 neutralizing antibodies (NAbs) and binding antibodies (BAbs) in human serum. The use of signal enhancer 3,3′-diaminobenzidine enabled the detection of NAbs, anti-receptor binding domain (anti-RBD) BAbs, and anti-extracellular domain of spike protein (anti-S-ECD) BAbs up to as low as 10 ng/mL in both buffer and 100-fold diluted serum. NAbs and BAbs could be detected individually over 7.5 and 13 min, respectively, or simultaneously by prolonging the detection time of the former. The protocol for the detection of BAbs could be utilized for detection of the RBD-N501Y variant with equal sensitivity and speed. Results of the NAbs and the anti-RBD BAbs biosensors correlated well with those of the corresponding commercial assay kit. Clinical utility of the two FO-BLI biosensors were further validated using a small cohort of samples randomly taken from 16 enrolled healthy participants who received inactivated vaccines. Two potent serum antibodies were identified, which showed high neutralizing capacities toward RBD and pseudovirus. Overall, the rapid automated biosensors can be used for an individual sample measurement of NAbs and BAbs as well as for high-throughput analysis. The findings of this study would be useful in COVID-19 related studies in vaccine trials, research on dynamics of the immune response, and epidemiology studies.

MRNA booster immunization elicits potent neutralizing serum activity against the SARS-CoV-2 Omicron variant

The Omicron variant of SARS-CoV-2 is causing a rapid increase in infections across the globe. This new variant of concern carries an unusually high number of mutations in key epitopes of neutralizing antibodies on the viral spike glycoprotein, suggesting potential immune evasion. Here we assessed serum neutralizing capacity in longitudinal cohorts of vaccinated and convalescent individuals, as well as monoclonal antibody activity against Omicron using pseudovirus neutralization assays. We report a near-complete lack of neutralizing activity against Omicron in polyclonal sera from individuals vaccinated with two doses of the BNT162b2 COVID-19 vaccine and from convalescent individuals, as well as resistance to different monoclonal antibodies in clinical use. However, mRNA booster immunizations in vaccinated and convalescent individuals resulted in a significant increase of serum neutralizing activity against Omicron. This study demonstrates that booster immunizations can critically improve the humoral immune response against the Omicron variant.

Candesartan, losartanand valsartan Zn(II) complexes interactions withbovine serum albumin.

Background: The pharmacological response and the therapeutic efficacy of a drug depends on the interactions with plasma proteins. Methodology: The interaction of bovine serum albumin (BSA) with themetal complexes of antihypertensive drugs, Zn(II)/sartan complexes (candesartan, valsartan andlosartan), was investigated using fluorescence quenching determinations at different temperatures. Results: The binding studies of the compounds with BSA showedstatic quenching and moderate binding with calculated constants in the range of 104-106M-1, indicating potent serum distribution via albumins. In all cases, negative values of free energy are indicative of spontaneous processes and the stabilization ofBSA/compound complexesthrough hydrogen bonding and van der Waals forces. The results for the sartans agree with thereported pharmacokinetics studies. Conclusion: It has been determined that the three sartans and the Zn complexes could be transported and distributed by albumin.

Evaluation of the efficacy of a novel Vibrio vulnificus vaccine based on antibacterial peptide inactivation in turbot, Scophthalmus maximus

Tongue sole tissue factor pathway inhibitor 2 (TFPI-2) C-terminus derived peptide, TC38, has previously been shown to kill Vibrio vulnificus cells without lysing the cell membrane; thus, the remaining bacterial shell has potential application as an inactivated vaccine. Therefore, this study aimed to evaluate the immune response induced by the novel V. vulnificus vaccine. The protective potential of TC38-killed V. vulnificus cells (TKC) was examined in a turbot model. Fish were intramuscularly vaccinated with TKC or FKC (formalin-killed V. vulnificus cells) and challenged with a lethal-dose of V. vulnificus. The results showed that compared with FKC, TKC was effective in protecting fish against V. vulnificus infection, with relative percent of survival (RPS) rates of 53.29% and 63.64%, respectively. The immunological analysis revealed that compared with the FKC and control groups, the TKC group exhibited: 1) significantly higher respiratory burst ability and bactericidal activity of macrophages at 7 d post-vaccination; 2) increased alkaline phosphatase, acid phosphatase, lysozyme, and total superoxide dismutase levels post-vaccination; 3) higher serum agglutinating antibody titer with corresponding higher serum bactericidal ability, and a more potent serum agglutination effect, as well as an increased IgM expression level; 4) higher expression of immune relevant genes, which were involved in both innate and adaptive immunity. Taken together, this is the first study to develop a novel V. vulnificus inactivated vaccine based on AMP inactivation, and TKC is an effective vaccine against V. vulnificus infection for aquaculture.

Isolation and characterization of cross-neutralizing coronavirus antibodies from COVID-19+ subjects.

SummarySARS-CoV-2 is one of three coronaviruses that have crossed the animal-to-human barrier and caused widespread disease in the past two decades. The development of a universal human coronavirus vaccine could prevent future pandemics. We characterize 198 antibodies isolated from four COVID-19+ subjects and identify 14 SARS-CoV-2 neutralizing antibodies. One targets the N-terminal domain (NTD), one recognizes an epitope in S2, and 11 bind the receptor-binding domain (RBD). Three anti-RBD neutralizing antibodies cross-neutralize SARS-CoV-1 by effectively blocking binding of both the SARS-CoV-1 and SARS-CoV-2 RBDs to the ACE2 receptor. Using the K18-hACE transgenic mouse model, we demonstrate that the neutralization potency and antibody epitope specificity regulates the in vivo protective potential of anti-SARS-CoV-2 antibodies. All four cross-neutralizing antibodies neutralize the B.1.351 mutant strain. Thus, our study reveals that epitopes in S2 can serve as blueprints for the design of immunogens capable of eliciting cross-neutralizing coronavirus antibodies.

Elicitation of potent serum neutralizing antibody responses in rabbits by immunization with an HIV-1 clade C trimeric Env derived from an Indian elite neutralizer.

Evaluating the structure-function relationship of viral envelope (Env) evolution and the development of broadly cross-neutralizing antibodies (bnAbs) in natural infection can inform rational immunogen design. In the present study, we examined the magnitude and specificity of autologous neutralizing antibodies induced in rabbits by a novel HIV-1 clade C Env protein (1PGE-THIVC) vis-à-vis those developed in an elite neutralizer from whom the env sequence was obtained that was used to prepare the soluble Env protein. The novel 1PGE-THIVC Env trimer displayed a native like pre-fusion closed conformation in solution as determined by small angle X-ray scattering (SAXS) and negative stain electron microscopy (EM). This closed spike conformation of 1PGE-THIVC Env trimers was correlated with weak or undetectable binding of non-neutralizing monoclonal antibodies (mAbs) compared to neutralizing mAbs. Furthermore, 1PGE-THIVC SOSIP induced potent neutralizing antibodies in rabbits to autologous virus variants. The autologous neutralizing antibody specificity induced in rabbits by 1PGE-THIVC was mapped to the C3/V4 region (T362/P401) of viral Env. This observation agreed with electron microscopy polyclonal epitope mapping (EMPEM) of the Env trimer complexed with IgG Fab prepared from the immunized rabbit sera. Our study demonstrated neutralization of sequence matched and unmatched autologous viruses by serum antibodies induced in rabbits by 1PGE-THIVC and also highlighted a comparable specificity for the 1PGE-THIVC SOSIP trimer with that seen with polyclonal antibodies elicited in the elite neutralizer by negative-stain electron microscopy polyclonal epitope (ns-EMPEM) mapping.

Serum and Cervicovaginal Fluid Antibody Profiling in Herpes Simplex Virus-Seronegative Recipients of the HSV529 Vaccine.

Previous herpes simplex virus type 2 (HSV-2) vaccines have not prevented genital herpes. Concerns have been raised about the choice of antigen, the type of antibody induced by the vaccine, and whether antibody is present in the genital tract where infection occurs. We reported results of a trial of an HSV-2 replication-defective vaccine, HSV529, that induced serum neutralizing antibody responses in 78% of HSV-1-/HSV-2- vaccine recipients. Here we show that HSV-1-/HSV-2- vaccine recipients developed antibodies to epitopes of several viral proteins; however, fewer antibody epitopes were detected in vaccine recipients compared with naturally infected persons. HSV529 induced antibodies that mediated HSV-2-specific natural killer (NK) cell activation. Depletion of glycoprotein D (gD)-binding antibody from sera reduced neutralizing titers by 62% and NK cell activation by 81%. HSV-2 gD antibody was detected in cervicovaginal fluid at about one-third the level of that in serum. A vaccine that induces potent serum antibodies transported to the genital tract might reduce HSV genital infection.

Serum bilirubin and chronic obstructive pulmonary disease (COPD): a systematic review

BackgroundBilirubin is a potent antioxidant and higher serum bilirubin levels have been associated with improved COPD outcomes. We performed a systematic review to evaluate the association between serum bilirubin levels and lung function (FEV1), prevalence/incidence of COPD, acute exacerbations of COPD, respiratory health status, and mortality.MethodsMEDLINE® and Embase were searched using Ovid® (search updated October 1st, 2019). We included studies that measured serum bilirubin levels and outcomes of interest in adults with or without underlying lung disease. We excluded studies of those with liver disease or drug-induced elevations in bilirubin. We used the Newcastle–Ottawa scale to assess individual study risk of bias (ROB) and the US Agency for Healthcare Research and Quality—Evidence Based Practice tool to assess overall strength of evidence (SOE). Two authors independently determined eligibility, performed data abstraction, assessed ROB, and determined SOE.ResultsThirteen studies (5 low risk of bias, 3 moderate and 5 high risk) were included. We found low strength of evidence for the association between higher bilirubin levels and lower risk of acute exacerbations of COPD (2 studies), mortality (3 studies), COPD diagnosis (4 studies), and lung function (FEV1) (8 studies). We found insufficient evidence on the relationship between serum bilirubin and respiratory health status/exercise capacity (1 study) and airflow obstruction (FEV1/FVC ratio) (4 studies).ConclusionHigher bilirubin levels may be associated with lower mortality and improved COPD outcomes. Randomized trials are needed to evaluate the effect of medications that raise serum bilirubin on COPD outcomes.PROSPERO registration: CRD42019145747.

One dose of COVID-19 nanoparticle vaccine REVC-128 protects against SARS-CoV-2 challenge at two weeks post-immunization

ABSTRACT A COVID-19 vaccine that can give early protection is needed to eliminate the viral spread efficiently. Here, we demonstrate the development of a nanoparticle vaccine candidate, REVC-128, in which multiple trimeric spike ectodomains with glycine (G) at position 614 were multimerized onto a nanoparticle. In-vitro characterization of this vaccine confirms its structural and antigenic integrity. In-vivo immunogenicity evaluation in mice indicates that a single dose of this vaccine induces potent serum neutralizing antibody titre at two weeks post-immunization. This is significantly higher than titre caused by trimeric spike protein without nanoparticle presentation. The comparison of serum binding to spike subunits between animals immunized by a spike with and without nanoparticle presentation indicates that nanoparticle prefers the display of spike RBD (Receptor-Binding Domain) over S2 subunit, likely resulting in a more neutralizing but less cross-reactive antibody response. Moreover, a Syrian golden hamster in-vivo model for the SARS-CoV-2 virus challenge was implemented two weeks post a single dose of REVC-128 immunization. The results showed that vaccination protects hamsters against the SARS-CoV-2 virus challenge with evidence of steady body weight, suppressed viral loads and alleviation of tissue damage for protected animals, compared with ∼10% weight loss, high viral loads and tissue damage in unprotected animals. Furthermore, the data showed that vaccine REVC-128 is thermostable at up to 37°C for at least 4 weeks. These findings, along with a history of safety for protein vaccines, suggest that the REVC-128 is a safe, stable and efficacious single-shot vaccine to give the earliest protection against SARS-CoV-2 infection.

Evaluation of Serum GDF15, AFP, and PIVKA-II as Diagnostic Markers for HBV-Associated Hepatocellular Carcinoma.

To evaluate the potential diagnostic value of growth differentiation factor 15 (GDF15) alone and its combination with protein induced by vitamin K absence-II (PIVKA-II) and alpha-fetoprotein (AFP) for hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). Serum levels of GDF15, PIVKA-II, and AFP were measured in 110 patients with HBV-associated HCC, 70 patients with HBV-related liver cirrhosis (LC), 70 patients with chronic hepatitis B (CHB), and 110 healthy patients. Serum GDF15 was positively related to the levels of PIVKA-II and AFP in patients with HCC (r = 0.352 and r = 0.378; all P <.0001). When the receiver operating characteristic (ROC) curve was plotted for patients with HCC vs all control patients, serum GDF15 had diagnostic parameters of an area under the curve (AUC) of 0.693, a sensitivity of 67.30%, and a specificity of 66.70%, which were lower than parameters for PIVKA-II and AFP (all P <.0001). When the ROC curve was plotted for patients with HCC vs patients with LC, the combination of GDF15 and PIVKA-II had the highest diagnostic accuracy of AUC and specificity as compared with other combinations (all P <.0001). We found that GDF15 is a potent serum marker for the detection of HBV-associated HCC and that PIVKA-II combined with GDF15 can improve diagnostic accuracy for HBV-associated HCC.