SARS-CoV-2 Delta derivatives impact on neutralization of Covishield recipient sera

The emergence of SARS-CoV-2 Delta variant and its derivatives has created grave public health problem worldwide. The high transmissibility associated with this variant has led to daily increase in the number of SARS-CoV-2 infections. Delta variant has slowly dominated the other variants of concern. Subsequently, Delta has further mutated to Delta AY.1 to Delta AY.126. Of these, Delta AY.1 has been reported from several countries including India and considered to be highly infectious and probable escape mutant. Considering the possible immune escape, we had already evaluated the efficacy of the BBV152 against Delta and Delta AY.1 variants. Here, we have evaluated the neutralizing potential of sera of COVID-19 naive vaccinees (CNV) immunized with two doses of vaccine, COVID-19 recovered cases immunized with two doses of vaccine (CRV) and breakthrough infections (BTI) post immunization with two doses of vaccine against Delta, Delta AY.1 and B.1.617.3 using 50% plaque reduction neutralization test (PRNT50). Our study observed low NAb titer in CNV group against all the variants compared to CRV and BTI groups. Delta variant has shown highest reduction of 27.3-fold in NAb titer among CNV group compared to other groups and variants. Anti-S1-RBD IgG immune response among all the groups was also substantiated with NAb response. Compromised neutralization was observed against Delta and Delta AY.1 compared B.1 in all three groups. However, it provided protection against severity of the disease and fatality.

Incorporation of apolipoprotein E into HBV–HCV subviral envelope particles to improve the hepatitis vaccine strategy

Hepatitis C is a major threat to public health for which an effective treatment is available, but a prophylactic vaccine is still needed to control this disease. We designed a vaccine based on chimeric HBV–HCV envelope proteins forming subviral particles (SVPs) that induce neutralizing antibodies against HCV in vitro. Here, we aimed to increase the neutralizing potential of those antibodies, by using HBV–HCV SVPs bearing apolipoprotein E (apoE). These particles were produced by cultured stable mammalian cell clones, purified and characterized. We found that apoE was able to interact with both chimeric HBV–HCV (E1-S and E2-S) proteins, and with the wild-type HBV S protein. ApoE was also detected on the surface of purified SVPs and improved the folding of HCV envelope proteins, but its presence lowered the incorporation of E2-S protein. Immunization of New Zealand rabbits resulted in similar anti-S responses for all rabbits, whereas anti-E1/-E2 antibody titers varied according to the presence or absence of apoE. Regarding the neutralizing potential of these anti-E1/-E2 antibodies, it was higher in rabbits immunized with apoE-bearing particles. In conclusion, the association of apoE with HCV envelope proteins may be a good strategy for improving HCV vaccines based on viral envelope proteins.

Intramuscular SARS-CoV-2 vaccines elicit varying degrees of plasma and salivary antibody responses as compared to natural infection

Vaccination induced antibody and T-cell immune responses are important for systemic protection from COVID-19. Because SARS-CoV-2 infects and is transmitted by oral-pharyngeal mucosa, we wished to test mucosal antibodies elicited by natural infection or intramuscular vaccine injection. In a non-randomized observational study, we measured antibodies against the SARS-CoV-2 RBD in plasma and saliva from convalescent or vaccinated individuals and tested their neutralizing potential using a replication competent rVSV-eGFP-SARS-CoV-2. We found IgG and IgA anti-RBD antibodies as well as neutralizing activity in convalescent plasma and saliva. Two doses of mRNA vaccination (BNT162b2 or mRNA-1273) induced high levels of IgG anti-RBD in saliva, a subset of whom also had IgA, and significant neutralizing activity. We detected anti-RBD IgG and IgA with significant neutralizing potential in the plasma of single dose Ad26.COV2.S vaccinated individuals, and we detected slight amounts of anti-RBD antibodies in matched saliva. The role of salivary antibodies in protection against SARS-CoV-2 infection is unknown and merits further investigation. This study was not designed to, nor did it study the full kinetics of the antibody response or protection from infection, nor did it address variants of SARS-CoV-2.

Comparable neutralization of SARS-CoV-2 Delta AY.1 and Delta in individuals sera vaccinated with BBV152

The recent emergence of the SARS-CoV-2 Variant of Concern B.1.617.2 (Delta) variant and its high transmissibility has led to the second wave in India. BBV152 a whole-virion inactivated SARS-CoV-2 vaccine used for mass immunization in India, showed a 65.2% protection against the Delta variant in a double-blind, randomized, multicentre, phase 3 clinical trial. Subsequently, Delta has been further mutated to Delta AY.1, AY.2, and AY.3. Of these, AY.1 variant was first detected in India in April 2021 and subsequently from twenty other countries as well. Here, we have evaluated the IgG antibody titer and neutralizing potential of sera of COVID-19 naive individuals full doses of BBV152 vaccine, COVID-19 recovered cases with full dose vaccines and breakthrough cases post-immunization BBV152 vaccines against Delta, Delta AY.1 and B.1.617.3. A reduction in neutralizing activity was observed with the COVID-19 naive individuals full vaccinated (1.3, 1.5, 1.9-fold), COVID-19 recovered cases with full BBV152 immunization (2.5, 3.5, 3.8-fold) and breakthrough cases post-immunization (1.9, 2.8, 3.5-fold) against Delta, Delta AY.1 and B.1.617.3 respectively compared to B.1 variant. A minor reduction was observed in the neutralizing antibody titer in COVID- 19 recovered cases full BBV152 vaccinated and post immunized infected cases compared to COVID-19 naive vaccinated individuals. However, with the observed high titers, the sera of individuals belonging to all the aforementioned groups they would still neutralize the Delta, Delta AY.1 and B.1.617.3 variants effectively.

Hidden fraction of Polish population immune to SARS-CoV-2 in May 2021

Population immunity to SARS-CoV-2 derives from two well-defined and controlled sources: vaccinations or diagnosed and registered cases of the disease. It may however also result from asymptomatic, oligosymptomatic, or even full-blown but undiagnosed and unregistered cases from which patients recovered at home. Here we present a population screening for SARS-CoV-2 specific IgG and IgA antibodies in Polish citizens (healthy adults, N=501) who had never been positively diagnosed with or vaccinated against SARS-CoV-2. Blood samples were collected in Wrocław (Lower Silesia) on 15th and 22nd May 2021. Sera from COVID-19 patients with a severe course (hospitalized) (N=43) or had been vaccinated (N=14) served as a positive control. The patients were tested with Microblot-Array COVID-19 IgG and IgA (quantitative) that contain specific SARS-CoV-2 antigens: NCP, RBD, Spike S2, E, ACE2, PLPro protein, as well as antigens for exclusion cross-reactivity with other coronaviruses: MERS-CoV, SARS-CoV, HCoV 229E Np, HCoV NL63 Np. Within the investigated population of healthy adults who had never been positively diagnosed with or vaccinated against SARS-CoV-2, we found that 35.5% (178 out of 501) were positive for SARS-CoV-2-specific IgG and 52.5% (263 out of 501) were positive for SARS-CoV-2-specific IgA; 21.6% of the investigated population developed virus-specific IgG or IgA while being asymptomatic. Anti-RBD IgG, which represents virus-neutralizing potential, was found in 25.6% of individuals (128 out of 501). These patients, though positive for anti-SARS-CoV-2 antibodies, cannot be identified in the public health system as convalescents due to undiagnosed infections, and they are considered unaffected by SARS-CoV-2. Their contribution to population immunity against COVID-19 should however be considered in predictions and modeling of the COVID-19 pandemic. Of note, the majority of the investigated population still lacked anti-RBD IgG protection (74.4%); thus the positive fraction is not sufficient for effective population immunity, and vaccination against COVID-19 is still of the most importance for controlling the pandemic.

Analysis of the potential of acid mine drainage generation from the neutralized coal mining tailings

Mining activities specifically Coal Mining have been long testified to be one of the major contributing factors to environmental crisis, with Acid Mine Drainage (AMD) as one of the leading indicators. The purpose of this study was to assess the potential of AMD generation from neutralized coal mining tailings. In order to achieve the ultimate objective of the study, analysis of chemical composition and mineral content of the tailings using XRF (X-Ray Fluorescence) and XRD (X-Ray Diffraction) respectively, lastly, a static analysis such as ABA (Acid Base Accounting) and TCLP (Toxic Characteristic Leaching Procedure) were also conducted. The results have shown that the studied tailing samples had relatively higher Acid Potential (19 kg CaCO3/t to 20 kg CaCO3/t) versus the Neutralizing Potential (NP) (14 kg CaCO3/t to 18 kg CaCO3/t). It was also found that the Net Neutralizing Potential Ratio (NNPR) is less than zero (-1.5 kg CaCO3/t to -5.40 kg CaCO3/t which indicates that the tailings have the potential to generate acid. The low concentration of CaO indicates acidic potential of the samples because CaO is a buffering mineral. Based on the results of the study, it was concluded that Mine Tailings has the potential to generate acid; therefore, the contamination to the nearby watercourses is extremely possible if necessary remedial actions should be considered.

Emerging SARS-CoV-2 variants of concern evade humoral immune responses from infection and vaccination

Emerging SARS-CoV-2 variants pose a threat to human immunity induced by natural infection and vaccination. We assessed the recognition of three variants of concern (B.1.1.7, B.1.351 and P.1) in cohorts of COVID-19 patients ranging in disease severity (n = 69) and recipients of the Pfizer/BioNTech vaccine (n = 50). Spike binding and neutralization against all three VOC was substantially reduced in the majority of samples, with the largest 4-7-fold reduction in neutralization being observed against B.1.351. While hospitalized COVID-19 patients and vaccinees maintained sufficient neutralizing titers against all three VOC, 39% of non-hospitalized patients did not neutralize B.1.351. Moreover, monoclonal neutralizing antibodies (NAbs) show sharp reductions in their binding kinetics and neutralizing potential to B.1.351 and P.1, but not to B.1.1.7. These data have implications for the degree to which pre-existing immunity can protect against subsequent infection with VOC and informs policy makers of susceptibility to globally circulating SARS-CoV-2 VOC.

Sequence-Signature Optimization Enables Improved Identification of Human HV6-1-Derived Class Antibodies That Neutralize Diverse Influenza A Viruses

Sequence signatures of multidonor broadly neutralizing influenza antibodies can be used to quantify the prevalence of B cells with virus-neutralizing potential to accelerate development of broadly protective vaccine strategies. Antibodies of the same class share similar recognition modes and developmental pathways, and several antibody classes have been identified that neutralize diverse group 1- and group 2-influenza A viruses and have been observed in multiple human donors. One such multidonor antibody class, the HV6-1-derived class, targets the stem region of hemagglutinin with extraordinary neutralization breadth. Here, we use an iterative process to combine informatics, biochemical, and structural analyses to delineate an improved sequence signature for HV6-1-class antibodies. Based on sequence and structure analyses of known HV6-1 class antibodies, we derived a more inclusive signature (version 1), which we used to search for matching B-cell transcripts from published next-generation sequencing datasets of influenza vaccination studies. We expressed selected antibodies, evaluated their function, and identified amino acid-level requirements from which to refine the sequence signature (version 2). The cryo-electron microscopy structure for one of the signature-identified antibodies in complex with hemagglutinin confirmed motif recognition to be similar to known HV6-1-class members, MEDI8852 and 56.a.09, despite differences in recognition-loop length. Threading indicated the refined signature to have increased accuracy, and signature-identified heavy chains, when paired with the light chain of MEDI8852, showed neutralization comparable to the most potent members of the class. Incorporating sequences of additional class members thus enables an improved sequence signature for HV6-1-class antibodies, which can identify class members with increased accuracy.

Comparison of two marketed effervescent fast relief formulations for antacid activity-an in vitro study

Background: Hyper-acidity is excessive formation of acid (pH=1.5-3.5) in the stomach by parietal cells which causes a burning sensation in the chest. The preservation of gastric acid insult is crucial because of the implications of hyperacidity in gastroesophageal reflux disease (GERD), peptic ulcers and duodenal ulcers. Acidity is controlled by use of some over-the-counter (OTC) antacid formulations containing magnesium or aluminum hydroxides.Methods: In the present study, the preliminary antacid test (PAT), the pH acid neutralizing capacity (ANC), acid neutralizing potential (ANP) along with buffering capacity of two well-known quick release formulations (F1 [Digene Ultra Fizz] and F2 [a standard, commercially available product]) were determined. Results: According to US pharmacopeia USP, both the antacid formulations passed the PAT test. PAT results revealed that the pH of the acid-antacid solution was higher in F1 (8.20±0.02) as compared to F2, (6.53±0.01). The ANC results revealed that F1 (46.89±0.6 mEq/dosage) had higher neutralizing capacity as compared to F2(30.12±1.3 mEq/dosage). Higher ANP was observed for F1 (245 mins), and it was 2.7 times that of F2 (90 min). The onset of action for both the antacids was <2 seconds. Additionally, buffering capacity was evidently observed during ANP analysis in the case of F1. Independent T test performed for all the tests revealed that the data obtained was highly significant (p<0.01).Conclusions: F1 showed high antacid and buffering properties when tested in vitro. The present study highlights the need for future research on specific OTC non-prescribed antacid formulations with respect to their price, efficacy and side effects.

Neutralization of B.1.1.28 P2 variant with sera of natural SARS-CoV-2 infection and recipients of BBV152 vaccine

The emergence of new SARS-CoV-2 variants has been a serious threat to the public health system and vaccination program. The variant of concerns have been the under investigation for their neutralizing potential against the currently available COVID-19 vaccines. Here, we have determined the neutralization efficacy of B.1.1.28.2 variant with the convalescent sera of individuals with natural infection and BBV152 vaccination. The two-dose vaccine regimen significantly boosted the IgG titer and neutralizing efficacy against both B.1.1.28.2 and D614G variants compared to that seen with natural infection. The study demonstrated 1.92 and 1.09 fold reductions in the neutralizing titer against B.1.1.28.2 variant in comparison with prototype D614G variant with sera of vaccine recipients and natural infection respectively.