Biology subjects

Shete, A.

Publications and source records attributed to Shete, A..

7 recordsLinked to original sources

bioRxiv2021

ZRC3308 monoclonal antibody cocktail shows protective efficacy in Syrian hamsters against SARS-CoV-2 infection

We have developed a monoclonal antibody (mAb) cocktail (ZRC-3308) comprising of ZRC3308-A7 and ZRC3308-B10 in the ratio 1:1 for COVID-19 treatment. The mAbs were designed to have reduced immune effector functions and increased circulation half-life. mAbs showed good binding affinities to non-competing epitopes on RBD of SARS-CoV-2 spike protein and were found neutralizing SARS-CoV-2 variants B.1, B.1.1.7, B.1.351, B.1.617.2 and B.1.617.2 AY.1 in vitro. The mAb cocktail demonstrated effective prophylactic and therapeutic activity against SARS-CoV-2 infection in Syrian hamsters. The antibody cocktail appears to be a promising candidate for the prophylactic use and for therapy in early COVID-19 cases which have not progressed to severe disease.

microbiology↗

bioRxiv2021

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.

molecular biology↗

bioRxiv2021

Isolation of SARS-CoV-2 B.1.1.28.2 P2 variant and pathogenicity comparison with D614G variant in hamster model

BackgroundConsidering the potential threat from emerging SARS-CoV-2 variants and the rising COVID-19 cases, SARS-CoV-2 genomic surveillance is ongoing in India. We report herewith the isolation of the P.2 variant (B.1.1.28.2) from international travelers and further its pathogenicity evaluation and comparison with D614G variant (B.1) in hamster model. MethodsVirus isolation was performed in Vero CCL81 cells and genomic characterization by next generation sequencing. The pathogenicity of the isolate was assessed in Syrian hamster model and compared with B.1 variant. ResultsB.1.1.28.2 variant was isolated from nasal/throat swabs of international travelers returned to India from United Kingdom and Brazil. The B.1.1.28.2 variant induced body weight loss, viral replication in the respiratory tract, lung lesions and caused severe lung pathology in infected Syrian hamster model in comparison, with B.1 variant infected hamsters. The sera from B.1.1.28.2 infected hamsters efficiently neutralized the D614G variant virus whereas 6-fold reduction in the neutralization was seen in case of D614G variant infected hamsters sera with the B.1.1.28.2 variant. ConclusionsB.1.1.28.2 lineage variant could be successfully isolated and characterization could be performed. Pathogenicity of the isolate was demonstrated in Syrian hamster model and in comparison, with B.1 variant was found more pathogenic. The findings of increased disease severity and neutralization reduction is of great concern and point towards the need for screening the vaccines for efficacy.

microbiology↗

bioRxiv2021

Isolation and characterization of SARS-CoV-2 VOC, 20H/501Y.V2, from UAE travelers

Multiple SARS-CoV-2 variants have been emerged and created serious public health in the affected countries. The variant of Concern associated with high transmissibility, disease severity and escape mutations is threat to vaccination program across the globe. Travel has been important factor in spread of SARS-CoV-2 variants worldwide. India has also witnessed the dreadful effect of these SARS-CoV-2 variants. Here, we report the Isolation and characterization of SARS-CoV-2 VOC, 20H/501Y.V2 (B.1.351), from UAE travelers to India. The virus isolate would be useful to determine the efficacy of the currently available vaccines in India.

microbiology↗

bioRxiv2021

Neutralization potential of Covishield vaccinated individuals against B.1.617.1

Covishield comprises the larger proportion in the vaccination program in India. Hence, it is of utmost importance to understand neutralizing capability of vaccine against the B.1.617.1 variant which is considered to responsible for surge of the cases in India. The neutralizing-antibody (NAb) titer against B.1.167.1 and prototype B.1 variant (D614G) was determined of the vaccine sera (4 weeks after second dose) of COVID-19 naive subjects (n=43) and COVID-19 recovered subjects (n=18). The results demonstrated that sera of COVID-19 recovered subjects (n=18) who received two doses of Covishield have higher NAb response compared to the COVID-19 naive with a significant difference (p<0.0001) in NAb titer against B.1 and B.1.617.1 In-spite of reduction in the neutralizing titer against B.1.617.1 variant; Covishield vaccine-induced antibodies are likely to be protective to limit the severity and mortality of the disease in the vaccinated individuals.

immunology↗

bioRxiv2021

Assessment of immunogenicity and protective efficacy of ZyCoV-D DNA vaccine candidates in Rhesus macaques against SARS-CoV-2 infection

Vaccines remain the key protective measure to achieve herd immunity to control the disease burden and stop COVID-19 pandemic. We have developed and assessed the immunogenicity and protective efficacy of two formulations (1mg and 2mg) of ZyCoV-D (a plasmid DNA based vaccine candidates) administered through Needle Free Injection System (NFIS) and syringe-needle (intradermal) in rhesus macaques with three dose vaccine regimens. The vaccine candidate 2mg dose administered using Needle Free Injection System (NFIS) elicited a significant immune response with development of SARS-CoV-2 S1 spike region specific IgG and neutralizing antibody (NAb) titers during the immunization phase and significant enhancement in the levels after the virus challenge. In 2 mg NFIS group the IgG and NAb titers were maintained and showed gradual rise during the immunization period (15 weeks) and till 2 weeks after the virus challenge. It also conferred better protection to macaques evident by the viral clearance from nasal swab, throat swab and bronchoalveolar lavage fluid specimens in comparison with macaques from other immunized groups. In contrast, the animals from placebo group developed high levels of viremia and lung disease following the virus challenge. Besides this, the vaccine candidate also induced increase lymphocyte proliferation and cytokines response (IL-6, IL-5).The administration of the vaccine candidate with NFIS generated a better immunogenicity response in comparison to syringe-needle (intradermal route). The study demonstrated immunogenicity and protective efficacy of the vaccine candidate, ZyCoV-D in rhesus macaques.

microbiology↗

bioRxiv2020

Evaluation of Safety and Immunogenicity of an Adjuvanted, TH-1 Skewed, Whole Virion Inactivated SARS-CoV-2 Vaccine - BBV152

We report the development and evaluation of safety and immunogenicity of a whole virion inactivated SARS-COV-2 vaccine (BBV152), adjuvanted with aluminium hydroxide gel (Algel), or a novel TLR7/8 agonist adsorbed Algel. We used a well-characterized SARS-CoV-2 strain and an established vero cell platform to produce large-scale GMP grade highly purified inactivated antigen, BBV152. Product development and manufacturing were carried out in a BSL-3 facility. Immunogenicity was determined at two antigen concentrations (3g and 6g), with two different adjuvants, in mice, rats, and rabbits. Our results show that BBV152 vaccine formulations generated significantly high antigen-binding and neutralizing antibody titers, at both concentrations, in all three species with excellent safety profiles. The inactivated vaccine formulation containing TLR7/8 agonist adjuvant-induced Th1 biased antibody responses with elevated IgG2a/IgG1 ratio and increased levels of SARS-CoV-2 specific IFN-{gamma}+ CD4 T lymphocyte response. Our results support further development for Phase I/II clinical trials in humans.

immunology↗