Immunogenicity of a Candidate Ebola Hemorrhagic Fever Vaccine in Mice Based on Controlled<i>In Vitro</i>Expression of<i>Ebolavirus</i>Glycoprotein

Kumar, Dilip; Gauthami, S.; Uma, Madala; Nagalekshmi, Karthika; Rao, P P; Basu, Atanu; Ella, Krishna M.; Hegde, Nagendra R.

doi:10.1089/vim.2017.0122

“…Adenoviruses are considered to be a safe and well-studied platform for antigen delivery ( 6 – 8 ), and have been used successfully to develop a COVID-19 vaccine ( 9 ). The chimpanzee Ad-vectored (Y25, a simian Ad-23) vaccine candidate ( 10 ) encoding the spike protein of MERS-CoV is protective in mice ( 11 ) and camels ( 12 ), and was shown to be safe and immunogenic in humans ( 13 ).…”

Section: Introductionmentioning

confidence: 99%

Preclinical evaluation of safety and immunogenicity of a primary series intranasal COVID-19 vaccine candidate (BBV154) and humoral immunogenicity evaluation of a heterologous prime-boost strategy with COVAXIN (BBV152)

Sunagar

¹

,

Prasad

²

,

Ella

³

et al. 2022

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Most if not all vaccine candidates developed to combat COVID-19 due to SARS-CoV-2 infection are administered parenterally. As SARS-CoV-2 is transmitted through infectious respiratory fluids, vaccine-induced mucosal immunity could provide an important contribution to control this pandemic. ChAd-SARS-CoV-2-S (BBV154), a replication-defective chimpanzee adenovirus (ChAd)-vectored intranasal (IN) COVID-19 vaccine candidate, encodes a prefusion-stabilized version of the SARS-CoV-2 spike protein containing two proline substitutions in the S2 subunit. We performed preclinical evaluations of BBV154 in mice, rats, hamsters and rabbits. Repeated dose toxicity studies presented excellent safety profiles in terms of pathology and biochemical analysis. IN administration of BBV154 elicited robust mucosal and systemic humoral immune responses coupled with Th1 cell-mediated immune responses. BBV154 IN vaccination also elicited potent variant (omicron) cross neutralization antibodies. Assessment of anti-vector (ChAd36) neutralizing antibodies following repeated doses of BBV154 IN administration showed insignificant titers of ChAd36 neutralizing antibodies. However, the immune sera derived from the same animals displayed significantly higher levels of SARS-CoV-2 virus neutralization (p<0.003). We also evaluated the safety and immunogenicity of heterologous prime-boost vaccination with intramuscular (IM) COVAXIN-prime followed by BBV154 IN administration. COVAXIN priming followed by BBV154 IN-booster showed an acceptable reactogenicity profile comparable to the homologous COVAXIN/COVAXIN or BBV154/BBV154 vaccination model. Heterologous vaccination of COVAXIN-prime and BBV154 booster also elicited superior (p<0.005) and cross variant (omicron) protective immune responses (p<0.013) compared with the homologous COVAXIN/COVAXIN schedule. BBV154 has successfully completed both homologous and heterologous combination schedules of human phase 3 clinical trials and received the restricted emergency use approval (in those aged above 18 years) from the Drugs Controller General of India (DCGI).

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Dual monoclonal antibody-based sandwich ELISA for detection of in vitro packaged Ebola virus

Zai

¹

,

Yang

²

,

Xie

³

et al. 2018

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BackgroundRapid transmission and high mortality of Ebola virus disease (EVD) highlight a urgent need of large scale, convenient and effective measure for Ebola virus screening. Application of monoclonal antibodies (mAbs) are crucial for establishment of an enzyme-linked immunosorbent assay (ELISA) with high sensitivity and specificity.MethodsThe traditional cell fusion technique was used to generate a panel of hybridomas. Two mAbs were characterized by SDS-PAGE, Western blot, Indirect immunofluorescence assay (IFA). A sandwich ELISA was established using the two mAbs. The detection capability of the ELISA was evaluated.ResultsIn the current study, we produced two murine-derived mAbs (designated as 6E3 and 3F21) towards Zaire Ebola virus glycoprotein (GP), the major viral transmembrane spike protein associated with viral attachment. It was shown that 6E3 and 3F21 recognized GP1 and GP2 subunits of the GP respectively. Furthermore, 6E3 and 3F21 bound to corresponding epitopes on GP without reciprocal topographical interpretation. Subsequently, a sandwich ELISA based on the two mAbs were established and evaluated. The detection limit was 3.6 ng/ml, with a linear range of 3.6–100 ng/ml. More importantly, Ebola virus like particles (eVLPs) were able to be detected by this established virus detection measure.ConclusionsWe produced and characterized two murine-derived mAbs (designated as 6E3 and 3F21) towards Zaire Ebola virus glycoprotein (GP), and established a sandwich ELISA based on the mAbs. It was suggested that the sandwich ELISA provided an alternative method for specific and sensitive detection of Ebola virus in the field setting.

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Preclinical evaluation of safety and immunogenicity of a primary series intranasal COVID-19 vaccine candidate (BBV154), and humoral immunogenicity evaluation of a heterologous prime-boost strategy with COVAXIN (BBV152)

Sunagar¹,

Prasad

²

,

Vadrevu

³

2022

Preprint

0

View full text Add to dashboard Cite

Most if not all vaccine candidates developed to combat COVID-19 due to SARS-CoV-2 infection are administered parenterally. As SARS-CoV-2 is transmitted through infectious respiratory fluids, vaccine-induced mucosal immunity could provide an important contribution to control this pandemic. ChAd-SARS-CoV-2-S (BBV154), a replication-defective chimpanzee adenovirus (ChAd)-vectored intranasal (IN) COVID-19 vaccine candidate, encodes a prefusion-stabilized version of the SARS-CoV-2 spike protein containing two proline substitutions in the S2 subunit. We performed preclinical evaluations of BBV154 in mice, rats, hamsters and rabbits. Repeated dose toxicity studies presented excellent safety profiles in terms of pathology and biochemical analysis. IN administration of BBV154 elicited robust mucosal and systemic humoral immune responses coupled with cell-mediated immune responses dominated by Th1-like cytokine expression. Heterologous prime-boost vaccination with intramuscular (IM) COVAXIN-prime followed by BBV154 intranasal in rabbits elicited superior immune responses compared with the homologous COVAXIN/COVAXIN schedule. BBV154 is now being assessed in both homologous and heterologous combination schedules in ongoing human clinical trials.

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Immunogenicity of a Candidate Ebola Hemorrhagic Fever Vaccine in Mice Based on ControlledIn VitroExpression ofEbolavirusGlycoprotein

Cited by 3 publications

References 73 publications

Preclinical evaluation of safety and immunogenicity of a primary series intranasal COVID-19 vaccine candidate (BBV154) and humoral immunogenicity evaluation of a heterologous prime-boost strategy with COVAXIN (BBV152)

Preclinical evaluation of safety and immunogenicity of a primary series intranasal COVID-19 vaccine candidate (BBV154) and humoral immunogenicity evaluation of a heterologous prime-boost strategy with COVAXIN (BBV152)

Dual monoclonal antibody-based sandwich ELISA for detection of in vitro packaged Ebola virus

Preclinical evaluation of safety and immunogenicity of a primary series intranasal COVID-19 vaccine candidate (BBV154), and humoral immunogenicity evaluation of a heterologous prime-boost strategy with COVAXIN (BBV152)

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