Effectiveness of Coronavirus Vaccines against Syndrome Coronavirus 2 (SARS-CoV-2) and Its New Variants

The widespread outbreak of coronavirus disease 2019 in late 2019 caused many people worldwide to die or suffer from certain clinical complications even after the recovery. The virus has many social and economic adverse effects. Studies on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have specified that spike, surface glycoprotein antigen, is considered as a major target to stimulate the immune system. This glycoprotein binds to the angiotensin-converting enzyme 2 on the surface of human cells especially lung epithelial cells and facilitates the virus entry. Therefore, the immune response stimulated by vaccination targeting this antigen may cause immunity against the whole virus. Currently, many companies are working on SARS-CoV-2 vaccines. They include ‘traditional’ vaccines like attenuated or inactivated virus platforms as well as the brand-new generations of vaccines such as viral vector-based, subunit, nucleic acid-based, and virus-like particle vaccines. Certainly, each vaccine platform presents several advantages and disadvantages affecting its efficacy and safety which is the main topic of this paper.

Chimeric Fusion (F) and Attachment (G) Glycoprotein Antigen Delivery by mRNA as a Candidate Nipah Vaccine

Nipah virus (NiV) represents a significant pandemic threat with zoonotic transmission from bats-to-humans with almost annual regional outbreaks characterized by documented human-to-human transmission and high fatality rates. Currently, no vaccine against NiV has been approved. Structure-based design and protein engineering principles were applied to stabilize the fusion (F) protein in its prefusion trimeric conformation (pre-F) to improve expression and increase immunogenicity. We covalently linked the stabilized pre-F through trimerization domains at the C-terminus to three attachment protein (G) monomers, forming a chimeric design. These studies detailed here focus on mRNA delivery of NiV immunogens in mice, assessment of mRNA immunogen-specific design elements and their effects on humoral and cellular immunogenicity. The pre-F/G chimera elicited a strong neutralizing antibody response and a superior NiV-specific Tfh and other effector T cell response compared to G alone across both the mRNA and protein platforms. These findings enabled final candidate selection of pre-F/G Fd for clinical development.

Highly individual- and tissue-specific expression of glycoprotein group A and B blood antigens in the human kidney and liver

Background Currently, research on the quantitative distribution of ABO antigens in different organs and tissues remains limited. We aimed to examine the individual characteristics of blood group glycoprotein A and B antigen expression in human kidneys and livers. Methods We obtained human samples, including the renal artery, renal vein, renal tissue, hepatic artery, hepatic vein, portal vein, and hepatic tissue, from 24 deceased organ transplant donors. The expression of the blood group antigens glycoprotein A and B was analysed and compared by Western blotting. Results There was no significant difference in the expression between blood group glycoprotein A and B antigens at any of the seven sites (p > 0.05). The expression of both A and B antigens was highest in renal tissue and the portal vein and was lowest in the renal artery. A large difference in glycoprotein antigen expression was observed among various donors or different regions of the same individual. Univariate analysis revealed that glycoprotein A/B antigens were affected by the age and sex of donors and were significantly higher in males and in young people. Conclusions Our study found that blood group glycoprotein antigen expression showed certain trends and distinct distribution in the kidney, liver, and vessels among individuals and in different regions of the same individual, which may explain the different clinical outcomes of patients who received ABO-incompatible transplantation.

Characterization of an Anti-Ebola virus Hyperimmune Globulin Derived from Convalescent Plasma

Backrgound Convalescent plasma has been used to treat many viral diseases including Ebola. The manufacture of a purified anti-Ebola virus (EBOV) intravenous immunoglobulin (IVIG) from pooled convalescent plasma is described in this paper. Methods An ELISA targeting an EBOV surface glycoprotein antigen was used to determine the immunoglobulin titer of pooled plasma and purified anti-EBOV IVIG. Anti-EBOV IVIG was also tested in neutralization assays using a vesicular stomatitis virus pseudovirion expressing EBOV glycoprotein on its surface and with live EBOV. Finally, the efficacy of the anti-EBOV IVIG was assessed in a mouse model of EBOV infection. Results In the ELISA, the anti-EBOV IVIG was shown to have a seven-fold increase in IgG titer over pooled convalescent plasma. In both the pseudovirion and live virus assays, the anti-EBOV IVIG showed approximately five- to six-fold increased potency over pooled plasma. Anti-EBOV IVIG also significantly improved survivability in mice infected with the virus when administered concurrently or two days after infection. Conclusions These data support this purified anti-EBOV IVIG merits additional investigation and clinical trials for treatment and post-exposure prophylaxis of Ebola virus disease. The experience gained can be applied to manufacture hyperimmune globulins against other emerging viruses.

A glycoengineered antigen exploiting a conserved protein O-glycosylation pathway in the Burkholderia genus for diagnosis of glanders infections

ABSTRACTWe recently described a protein O-glycosylation pathway conserved in all species of the Burkholderia genus that results in synthesis and incorporation of a trisaccharide glycan to membrane-exported proteins. Here, we exploited this system to construct and evaluate a diagnostic tool for glanders. Burkholderia mallei, the causative agent of glanders, is a highly infectious and fatal zoonotic pathogen that mainly infects horses, mules, donkeys and occasionally humans. A highly sensitive and specific diagnostic tool is crucial for the control, elimination and eradication of B. mallei infections. We constructed plasmids carrying synthetic genes encoding a modified, previously unannotated Burkholderia glycoprotein containing three glycosylation sequons fused to the cholera toxin B-subunit. The resulting proteins were glycosylated in the B. cenocepacia K56-2 parental strain, but not in glycosylation-deficient mutants, as determined by SDS-PAGE and fluorescent lectin blots. One of these glycoproteins was used as an antigen in ELISA and western blots to screen a panel of serum samples collected from glanders-infected and healthy horses previously investigated by complement fixation test and indirect ELISA based on a semi-purified fraction of B. mallei. We show that ELISA and western blot assays based on our glycoprotein antigen provide 100 % specificity, with a sensitivity greater than 88%. The glycoprotein antigen was recognized by serum samples collected from patients infected with B. pseudomallei, B. mallei, B. multivorans and B. cenocepacia. Our results indicate that protein O-glycosylation in Burkholderia can be exploited as a biomarker for diagnosis of Burkholderia-associated infections.IMPORTANCEGlanders is a severe zoonotic disease caused by the Gram-negative bacterium Burkholderia mallei, which affects horses, mules and donkeys, as well as humans. B. mallei is also considered a category B biothreat agent. Due to insufficient pathognomonic symptoms in the early stages of glanders, diagnosis can be difficult. Complement fixation is the most accurate and reliable serological test prescribed by the World Organization for Animal Health; however, this test has a considerable number of false-positive results. We have recently described a conserved protein O-glycosylation pathway present in all species of the Burkholderia genus; we also demonstrated that Burkholderia-infected humans develop anti-glycan antibodies. Here, we exploited this system to construct and evaluate a synthetic glycoengineered protein antigen as a diagnostic tool for glanders. Our results show 100 % specificity in the detection of antibodies from infected horses, indicating that protein O-glycosylation in Burkholderia can be exploited as a biomarker for diagnosis of Burkholderia-associated infections.

Recent updates on CAR T clinical trials for multiple myeloma

Proteasome inhibitors, immunomodulatory agents and monoclonal antibodies have dramatically changed the natural history of multiple myeloma (MM). However, most patients eventually suffer a relapse and succumb to the disease. Chimeric antigen receptor (CAR) engineered T cells targeting B cell maturation antigen (BCMA), CD138, CS1 glycoprotein antigen (SLAMF7) and light chains are in active development for therapy of refractory /relapsed (RR) MM. CD19- targeted CAR T cells in conjunction with autologous stem cell transplantation also showed activity in RRMM. Dual- target CAR T cells are in clinical trials for RRMM. This review summarized the recent updates of ongoing CAR T clinical trials for multiple myeloma.

Role of CA 19-9 in complex ovarian tumors

Background: Cancer antigen 19-9 (CA 19-9) is a tumor-associated mucin glycoprotein antigen that may be elevated in healthy individuals as well as in patients with benign and malignant tumors. It is useful in the management of pancreatic and other gastrointestinal tumors. CA 19-9 is also elevated in benign and malignant ovarian tumors. Aim: To study the pattern of serum CA19-9 in complex ovarian tumors. Methods: The study design was descriptive, based on data collected from medical records. Patients with a complex ovarian mass, who were investigated with CA 19-9 and had undergone surgery, wereincluded in the study. The study duration was 2 years from January 2014 to December 2015. A total of 273 patients (119 - benign and 154 malignant) with complex ovarian mass and elevated CA 19-9 underwent surgery during the study period. Results: CA 19-9 was elevated in 55 patients (20%). Of these, 23 patients had benign tumors while 32 had malignant tumors.Among patients with benign tumors, 21 had dermoid, 23 had mucinous tumors and 75 had other types of tumors. CA 19-9 was elevated in 10 (47.6%) of the dermoids, 7 (30.4%) of the mucinous tumors and 6 (8%) of the other benign tumors. Among patients with malignant tumors, 138 were epithelial and 16 were non epithelial tumors. Of the epithelial tumors, 31 were mucinous and 107 were non mucinous types. Overall, 29 (21%) had elevated CA 19-9. Of the epithelial tumors, 22.6% of the mucinous type and 20.6% of the non mucinous type had elevated CA 19-9. Among the non-epithelial tumors, 3 (18.8%) had elevated CA19-9. Conclusion: CA 19-9 is elevated in several conditions but most likely to be raised in dermoid cysts and mucinous tumours. CA19-9 levels need to be interpreted along with clinical and radiological findings.

Role of cancer antigen 19-9 in complex ovarian tumors

Background: Cancer antigen 19-9 (CA 19-9) is a tumor-associated mucin glycoprotein antigen that may be elevated in healthy individuals as well as in patients with benign and malignant tumors. It is useful in the management of pancreatic and other gastrointestinal tumors. CA 19-9 is also elevated in benign and malignant ovarian tumors. Aim: To study the pattern of serum CA 19-9 in complex ovarian tumors. Methods: The study design was descriptive, based on data collected from medical records. Patients with a complex ovarian mass, who were investigated with CA 19-9 and had undergone surgery, were included in the study. The study duration was 2 years from January 2014 to December 2015. A total of 273 patients (119 benign and 154 malignant) with complex ovarian mass and elevated CA 19-9 underwent surgery during the study period. Results: CA 19-9 was elevated in 55 patients (20%). Of these, 23 patients had benign tumors while 32 had malignant tumors. Among patients with benign tumors, 21 had dermoid, 23 had mucinous tumors and 75 had other types of tumors. CA 19-9 was elevated in 10 (47.6%) of the dermoids, 7 (30.4%) of the mucinous tumors and 6 (8%) of the other benign tumors. Among patients with malignant tumors, 138 were epithelial and 16 were non epithelial tumors. Of the epithelial tumors, 31 were mucinous and 107 were nonmucinous types. Overall, 29 (21%) had elevated CA 19-9. Of the epithelial tumors, 22.6% of the mucinous type and 20.6% of the non mucinous type had elevated CA 19-9. Among the non-epithelial tumors, 3 (18.8%) had elevated CA19-9. Conclusion: CA 19-9 is elevated in several conditions but most likely to be raised in dermoid cysts and mucinous tumours. CA19-9 levels need to be interpreted along with clinical and radiological findings.