The DOI matches its Crossref record; 44 of the 47 references it cites were found in a registry or an index.
Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: a double-blind, randomised, phase 1 trial
Open accessPublished version of a preprint
Abstract
Background To mitigate the effects of COVID-19, a vaccine is urgently needed. BBV152 is a whole-virion inactivated SARS-CoV-2 vaccine formulated with a toll-like receptor 7/8 agonist molecule adsorbed to alum (Algel-IMDG) or alum (Algel).Methods We did a double-blind, multicentre, randomised, controlled phase 1 trial to assess the safety and immunogenicity of BBV152 at 11 hospitals across India. Healthy adults aged 18-55 years who were deemed healthy by the investigator were eligible. Individuals with positive SARS-CoV-2 nucleic acid and/or serology tests were excluded. Participants were randomly assigned to receive either one of three vaccine formulations (3 μg with Algel-IMDG, 6 μg with Algel-IMDG, or 6 μg with Algel) or an Algel only control vaccine group. Block randomisation was done with a web response platform. Participants and investigators were masked to treatment group allocation. Two intramuscular doses of vaccines were administered on day 0 (the day of randomisation) and day 14. Primary outcomes were solicited local and systemic reactogenicity events at 2 h and 7 days after vaccination and throughout the full study duration, including serious adverse events. Secondary outcome was seroconversion (at least four-fold increase from baseline) based on wild-type virus neutralisation. Cell-mediated responses were evaluated by intracellular staining and ELISpot. The trial is registered at ClinicalTrials.gov (NCT04471519).Findings Between July 13 and 30, 2020, 827 participants were screened, of whom 375 were enrolled. Among the enrolled participants, 100 each were randomly assigned to the three vaccine groups, and 75 were randomly assigned to the control group (Algel only). After both doses, solicited local and systemic adverse reactions were reported by 17 (17%; 95% CI 10·5-26·1) participants in the 3 μg with Algel-IMDG group, 21 (21%; 13·8-30·5) in the 6 μg with Algel-IMDG group, 14 (14%; 8·1-22·7) in the 6 μg with Algel group, and ten (10%; 6·9-23·6) in the Algel-only group. The most common solicited adverse events were injection site pain (17 [5%] of 375 participants), headache (13 [3%]), fatigue (11 [3%]), fever (nine [2%]), and nausea or vomiting (seven [2%]). All solicited adverse events were mild (43 [69%] of 62) or moderate (19 [31%]) and were more frequent after the first dose. One serious adverse event of viral pneumonitis was reported in the 6 μg with Algel group, unrelated to the vaccine. Seroconversion rates (%) were 87·9, 91·9, and 82·8 in the 3 μg with Algel-IMDG, 6 μg with Algel-IMDG, and 6 μg with Algel groups, respectively. CD4+ and CD8+ T-cell responses were detected in a subset of 16 participants from both Algel-IMDG groups.Interpretation BBV152 led to tolerable safety outcomes and enhanced immune responses. Both Algel-IMDG formulations were selected for phase 2 immunogenicity trials. Further efficacy trials are warranted.Funding Bharat Biotech International.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“For example, anti-nucleocapsid as well as anti-S binding antibodies are elicited by the whole-cell inactivated vaccine BBV152 (ref.100)”
From Immunological mechanisms of vaccine-induced protection against COVID-19 in humans (2021) · cites this paper as [100]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
WHO Coronavirus Disease (COVID-19) Dashboard
e, C. R. D. I. (2020) · Bangladesh Physiotherapy Journal · doi:10.46945/bpj.10.1.03.01 · Cited by 5,465
Korber, B., Fischer, W. M., Gnanakaran, S., Yoon, H., Theiler, J., Abfalterer, W., Hengartner, N., Giorgi, E. E., Bhattacharya, T., Foley, B., et al. (2020) · Cell · doi:10.1016/j.cell.2020.06.043 · Cited by 4,281
Grifoni, A., Weiskopf, D., Ramirez, S. I., Mateus, J., Dan, J. M., Moderbacher, C. R., Rawlings, S. A., Sutherland, A., Premkumar, L., Jadi, R. S., et al. (2020) · Cell · doi:10.1016/j.cell.2020.05.015 · Cited by 3,595
An mRNA Vaccine against SARS-CoV-2 — Preliminary Report
Jackson, L. A., Anderson, E. J., Rouphael, N. G., Roberts, P. C., Makhene, M., Coler, R. N., McCullough, M. P., Chappell, J. D., Denison, M. R., Stevens, L. J., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2022483 · Cited by 3,237
RNA-Based COVID-19 Vaccine BNT162b2 Selected for a Pivotal Efficacy Study
Walsh, E. E., Frenck, R., Falsey, A. R., Kitchin, N., Absalon, J., Gurtman, A., Lockhart, S., Neuzil, K., Mulligan, M. J., Bailey, R., et al. (2020) · doi:10.1101/2020.08.17.20176651 · Cited by 2,615
Folegatti, P. M., Ewer, K. J., Aley, P. K., Angus, B., Becker, S., Belij-Rammerstorfer, S., Bellamy, D., Bibi, S., Bittaye, M., Clutterbuck, E. A., et al. (2020) · The Lancet · doi:10.1016/s0140-6736(20)31604-4 · Cited by 2,419
Mulligan, M. J., Lyke, K. E., Kitchin, N., Absalon, J., Gurtman, A., Lockhart, S., Neuzil, K., Raabe, V., Bailey, R., Swanson, K. A., et al. (2020) · doi:10.1101/2020.06.30.20142570 · Cited by 1,569
Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults
Anderson, E. J., Rouphael, N. G., Widge, A. T., Jackson, L. A., Roberts, P. C., Makhene, M., Chappell, J. D., Denison, M. R., Stevens, L. J., Pruijssers, A. J., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2028436 · Cited by 1,523
Zhang, Y., Zeng, G., Pan, H., Li, C., Hu, Y., Chu, K., Han, W., Chen, Z., Tang, R., Yin, W., et al. (2021) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(20)30843-4 · Cited by 1,504
Zhu, F.-C., Li, Y.-H., Guan, X.-H., Hou, L.-H., Wang, W.-J., Li, J.-X., Wu, S.-P., Wang, B.-S., Wang, Z., Wang, L., et al. (2020) · The Lancet · doi:10.1016/s0140-6736(20)31208-3 · Cited by 1,382
Toll-like receptors control activation of adaptive immune responses
Schnare, M., Barton, G. M., Czopik, A. K., Takeda, K., Akira, S., & Medzhitov, R. M. (2001) · Nature Immunology · doi:10.1038/ni712 · Cited by 1,364
Zhu, F.-C., Guan, X.-H., Li, Y.-H., Huang, J.-Y., Jiang, T., Hou, L.-H., Li, J.-X., Yang, B.-F., Wang, L., Wang, W.-J., et al. (2020) · The Lancet · doi:10.1016/s0140-6736(20)31605-6 · Cited by 1,225
Xia, S., Zhang, Y., Wang, Y., Wang, H., Yang, Y., Gao, G. F., Tan, W., Wu, G., Xu, M., Lou, Z., et al. (2020) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(20)30831-8 · Cited by 1,129
Weiskopf, D., Schmitz, K. S., Raadsen, M. P., Grifoni, A., Okba, N. M. A., Endeman, H., van den Akker, J. P. C., Molenkamp, R., Koopmans, M. P. G., van Gorp, E. C. M., et al. (2020) · Science Immunology · doi:10.1126/sciimmunol.abd2071 · Cited by 907
Rapid COVID-19 vaccine development
Graham, B. S. (2020) · Science · doi:10.1126/science.abb8923 · Cited by 771
Effect of an Inactivated Vaccine Against SARS-CoV-2 on Safety and Immunogenicity Outcomes
Xia, S., Duan, K., Zhang, Y., Zhao, D., Zhang, H., Xie, Z., Li, X., Peng, C., Zhang, Y., Zhang, W., et al. (2020) · JAMA · doi:10.1001/jama.2020.15543 · Cited by 768
Delgado, M. F., Coviello, S., Monsalvo, A. C., Melendi, G. A., Hernandez, J. Z., Batalle, J. P., Diaz, L., Trento, A., Chang, H.-Y., Mitzner, W., et al. (2008) · Nature Medicine · doi:10.1038/nm.1894 · Cited by 498
A perspective on potential antibody-dependent enhancement of SARS-CoV-2
Arvin, A. M., Fink, K., Schmid, M. A., Cathcart, A., Spreafico, R., Havenar-Daughton, C., Lanzavecchia, A., Corti, D., & Virgin, H. W. (2020) · Nature · doi:10.1038/s41586-020-2538-8 · Cited by 485
Human Vaccines & Immunotherapeutics
Riedmann, E. M. (2013) · Human Vaccines & Immunotherapeutics · doi:10.4161/hv.26189 · Cited by 462
Advances in aluminum hydroxide-based adjuvant research and its mechanism
Peng, H., Zou, Y., & Hu, Z. (2015) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2014.1004026 · Cited by 415
Bhandari, N., Rongsen‐Chandola, T., Bavdekar, A., John, J. K., Antony, K., Taneja, S., Goyal, N. P., Kawade, A. S., Kang, G., Rathore, S. S., et al. (2014) · The Lancet · doi:10.1016/s0140-6736(13)62630-6 · Cited by 328
Self-citationD614G Spike Mutation Increases SARS CoV-2 Susceptibility to Neutralization
Weissman, D., Alameh, M.-G., de Silva, T., Collini, P., Hornsby, H., Brown, R., LaBranche, C. C., Edwards, R. J., Sutherland, L., Santra, S., et al. (2021) · Cell Host & Microbe · doi:10.1016/j.chom.2020.11.012 · Cited by 324
Geeraedts, F., Goutagny, N., Hornung, V., Severa, M., de Haan, A., Pool, J., Wilschut, J., Fitzgerald, K. A., & Huckriede, A. L. W. (2008) · PLoS Pathogens · doi:10.1371/journal.ppat.1000138 · Cited by 237
COVID-19 vaccine design: the Janus face of immune enhancement
Hotez, P. J., Corry, D. B., & Bottazzi, M. E. (2020) · Nature reviews. Immunology · doi:10.1038/s41577-020-0323-4 · Cited by 168
Philbin, V. J., Dowling, D. J., Gallington, L. C., Cortés, G., Tan, Z. W., Suter, E. E., Chi, K. W., Shuckett, A., Stoler‐Barak, L., Tomai, M. A., et al. (2012) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2012.02.042 · Cited by 116
First isolation of SARS-CoV-2 from clinical samples in India
Sarkale, P., Patil, S., Yadav, P. D., Nyayanit, D. A., Sapkal, G. N., Baradkar, S., Lakra, R., Shete-Aich, A., Prasad, S., Basu, A., et al. (2020) · The Indian Journal of Medical Research · doi:10.4103/ijmr.ijmr_1029_20 · Cited by 112
Self-citationThe Challenges of Vaccine Development against a New Virus during a Pandemic
Diamond, M., & Pierson, T. C. (2020) · Cell Host & Microbe · doi:10.1016/j.chom.2020.04.021 · Cited by 108
Yadav, P. D., Ella, R., Kumar, S., Patil, D., Mohandas, S., Shete, A. M., Vadrevu, K. M., Bhati, G., Sapkal, G. N., Kaushal, H., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-21639-w · Cited by 105
Self-citationBhandari, N., Rongsen‐Chandola, T., Bavdekar, A., John, J. K., Antony, K., Taneja, S., Goyal, N. P., Kawade, A. S., Kang, G., Rathore, S. S., et al. (2014) · Vaccine · doi:10.1016/j.vaccine.2014.04.079 · Cited by 102
Self-citationZhang, Y., Zeng, G., Pan, H., et al. (2020) · medRxiv · doi:10.1101/2020.07.31.20161216 · Cited by 96
Mohandas, S., Yadav, P. D., Shete-Aich, A., Abraham, P., Vadrevu, K. M., Sapkal, G., Mote, C., Nyayanit, D., Gupta, N., Srinivas, V. K., et al. (2021) · iScience · doi:10.1016/j.isci.2021.102054 · Cited by 74
Self-citationD614G Spike Mutation Increases SARS CoV-2 Susceptibility to NeutralizationPreprint
Weissman, D., Alameh, M., de Silva, T. I., Collini, P., Hornsby, H. R., Brown, R. L., LaBranche, C. C., Edwards, R. J., Sutherland, L. L., Santra, S., et al. (2020) · medRxiv · doi:10.1101/2020.07.22.20159905 · Cited by 72
Singh, A., Mitra, M., Sampath, G., Venugopal, P., Rao, J. V., Krishnamurthy, B., Gupta, M. K., Krishna, S., Sudhakar, B., Rao, N. B., et al. (2015) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiv023 · Cited by 72
Self-citationPotent Adjuvanticity of a Pure TLR7-Agonistic Imidazoquinoline Dendrimer
Shukla, N. M., Salunke, D. B., Balakrishna, R., Mutz, C. A., Malladi, S. S., & David, S. A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0043612 · Cited by 71
Potdar, V. A., Cherian, S. S., Deshpande, G. R., Ullas, P. T., Yadav, P. D., Choudhary, M. L., Gughe, R., Vipat, V., Jadhav, S., Patil, S., et al. (2020) · The Indian Journal of Medical Research · doi:10.4103/ijmr.ijmr_1058_20 · Cited by 46
Self-citationJohnson, T. R., & Graham, B. S. (2004) · The Pediatric Infectious Disease Journal · doi:10.1097/01.inf.0000108192.94692.d2 · Cited by 44
Ganneru, B., Jogdand, H., Daram, V. K., Molugu, N. R., Prasad, S. D., Vellimudu, S., Ella, K. M., Ravikrishnan, R., Awasthi, A., Jose, J., et al. (2020) · SSRN Electronic Journal · doi:10.1101/2020.09.09.285445 · Cited by 30
Self-citationVadrevu, K. M., Potula, V., Khalatkar, V. M., Mahantshetty, N. S., Shah, A., & Ella, R. (2019) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiz672 · Cited by 25
Self-citationYadav, P., Ella, R., Kumar, S., Patil, D. R., Mohandas, S., Shete, A., Bhati, G., Sapkal, G., Kaushal, H., Patil, S., et al. (2020) · Research Square · doi:10.21203/rs.3.rs-65715/v1 · Cited by 24
Self-citationElla, R., Bobba, R., Muralidhar, S., Babji, S., Vadrevu, K. M., & Bhan, M. K. (2018) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2018.1450709 · Cited by 21
Self-citationSampath, G., Madhusudana, S. N., Sudarshan, M. K., Ashwathnarayana, D. H., Mahendra, B. J., Ullas, P. T., Surapaneni, K. M., Madhusudhan, S. K., & Ravish, H. S. (2010) · Vaccine · doi:10.1016/j.vaccine.2010.03.064 · Cited by 20
Ella, R., Babji, S., Ciarlet, M., Blackwelder, W. C., & Vadrevu, K. M. (2019) · Vaccine · doi:10.1016/j.vaccine.2019.05.069 · Cited by 17
Self-citationGraepel, K. W., Kochhar, S., Clayton, E. W., & Edwards, K. E. (2020) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiaa234 · Cited by 15
Mohandas, S., Yadav, P. D., Shete, A. M., Abraham, P., Surapaneni, K. M., Sapkal, G. N., Mote, C., Nyayanit, D. A., Gupta, N., Srini, V. K., et al. (2020) · doi:10.21203/rs.3.rs-76768/v1 · Cited by 10
Self-citation
Research works printed but not linked: 2
- Mulligan, 2020, Phase I/II study of COVID-19 RNA vaccine BNT162b1 in adults, Nature, 586, 589, 10.1038/s41586-020-2639-4 · DOI · Paper page
- Walsh, 2020, Safety and immunogenicity of two RNA-based Covid-19 vaccine candidates, N Engl J Med, 10.1056/NEJMoa2027906 · DOI · Paper page
Cited by
Sorted by citations
Mechanisms of SARS-CoV-2 entry into cells
Jackson, C. B., Farzan, M., Chen, B., & Choe, H. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00418-x · Cited by 3,022
Emerging concepts in the science of vaccine adjuvants
Pulendran, B., Arunachalam, P. S., & O’Hagan, D. T. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00163-y · Cited by 1,446
Tanriover, M. D., Doğanay, H. L., Akova, M., Güner, H. R., Azap, A., Akhan, S., Köse, Ş., Erdinç, F. Ş., Akalın, E. H., Tabak, Ö. F., et al. (2021) · The Lancet · doi:10.1016/s0140-6736(21)01429-x · Cited by 898
Advances in COVID-19 mRNA vaccine development
Fang, E., Liu, X., Li, M., Zhang, Z., Song, L., Zhu, B., Wu, X., Liu, J., Zhao, D., & Li, Y. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00950-y · Cited by 601
Immunological mechanisms of vaccine-induced protection against COVID-19 in humans
Sadarangani, M., Marchant, A., & Kollmann, T. R. (2021) · Nature Reviews Immunology · doi:10.1038/s41577-021-00578-z · Cited by 560
Metadata
- Authors
- Ella, R., Vadrevu, K. M., Jogdand, H., Prasad, S., Reddy, S., Sarangi, V., Ganneru, B., Sapkal, G., Yadav, P., Abraham, P., Panda, S., Gupta, N., Reddy, P., Verma, S., Kumar Rai, S., Singh, C., Redkar, S. V., Gillurkar, C. S., Kushwaha, J. S., Mohapatra, S., Rao, V., Guleria, R., Ella, K., & Bhargava, B.
- Affiliations
- Bharat Biotech (India) (IN)
- ICMR-National Institute of Virology (IN)
- Indian Council of Medical Research (IN)
- Nizam's Institute of Medical Sciences (IN)
- Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences (IN)
- All India Institute of Medical Sciences, Patna (IN)
- SRM Medical College Hospital and Research Centre (IN)
- Institute of Medical Sciences and Sum Hospital (IN)
- All India Institute of Medical Sciences (IN)
- Corresponding author
- Vadrevu, Krishna Mohan
- ORCID
- Venue
- The Lancet Infectious Diseases
- Publisher
- Elsevier BV
- Published
- 2021-05
- Volume
- 21
- Issue
- 5
- Pages
- 637-646
- ISSN
- 1473-3099 (ISSN-L)
- PMC
- PMC7825810
- OpenAlex
- W3121691244
- Cited by
- 424
- References
- 47
- Citations by year
- 2026: 12 · 2025: 14 · 2024: 32 · 2023: 64 · 2022: 135 · 2021: 164
- FWCI
- 31.25
- Type
- journal article
- Language
- en
- Update notices
- Open access
- bronze
- doi.org
- Licence
- Locations
- The Lancet Infectious Diseases (publishedVersion)
- medRxiv (acceptedVersion, cc-by-nd)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- BBV152, inactivated SARS-CoV-2 vaccine, COVID-19 vaccines, vaccine safety, vaccine immunogenicity, alum adjuvant, Toll-like receptor 7/8 agonist, reactogenicity, seroconversion, neutralizing antibodies, cell-mediated immunity, dose comparison, healthy adults, India
- MeSH terms
- COVID-19, SARS-CoV-2, COVID-19 Vaccines, Adolescent, Adult, Antibodies, Viral, Double-Blind Method, Female, Humans, Immunoglobulin G, Male, Middle Aged, Vaccination, Vaccines, Inactivated, Toll-Like Receptor 7, Toll-Like Receptor 8, Young Adult, Antibodies, Neutralizing
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
