Efficacy, safety, and lot-to-lot immunogenicity of an inactivated SARS-CoV-2 vaccine (BBV152): interim results of a randomised, double-blind, controlled, phase 3 trial

Ella, Raches; Reddy, Siddarth; Blackwelder, William C.; Potdar, Varsha; Yadav, Pragya D; Sarangi, Vamshi; Aileni, Vinay Kumar; Kanungo, Suman; Rai, Sanjay; Reddy, Prabhakar; Verma, Savita; Singh, Chandramani; Mohapatra, Satyakam; Pandey, Anil; Ranganadin, Pajanivel; Gumashta, Raghvendra; Multani, Manish Kishore; Shameem, Mohammad; Bhatt, Parloop; Kumar, Sanjay; Sapkal, Gajanan; Gupta, Nivedita; Abraham, Priya; Panda, Samiran; Prasad, Sai; Bhargava, Balram; Ella, Krishna M.; Vadrevu, Krishna Mohan; Aggarwal, Pradeep; Aglawe, V.; Ali, Aabidah; Anand, Nitin; Awad, N.; Bafna, Varun; Balasubramaniyam, G.; Bandkar, A.; Basha, P. Mahaboob; Bharge, V.; Bhate, Amit Suresh; Bhate, Sameer; Bhavani, V.; Bhosale, Ramesh; Chalapathy, DV; Chaubal, C.; Chaudhary, Deepak; Chavan, Ashish; Desai, Parth; Dhodi, Dinesh K; Dutta, Siddhartha; Garg, Rakesh; Garg, Kapil; George, Melvin; Goyal, Pankaj; Guleria, Randeep; Gupta, Sneh Lata; Jain, Mansi; Jindal, S. K.; Kalra, Manju; Kant, Shashi; Khosla, Pooja; Kulkarni, Prasad S.; Kumar, Pradeep; Kumar, Y; Majumdar, Anish Sen; Meshram, Priti; Mishra, Vaibhav; Mohanty, Sneha; Nair, Julie McCulloh; Pandey, Shivam; Panigrahi, Suryanarayan; Patil, Bapugouda Sahebagouda; Patil, Vasant; Rahate, Prashant; Raj, Venkatachalum B.; Ramanand, Sunita J.; Rami, Kiran; Ramraj, Balaji; Rane, Shraddha; Epari, Venkatarao; Rao, N.; Raphael, Renée; Reddy, G Ravi Chandra; Redkar, Vivek; Redkar, Sagar Vivek; Sachdeva, Ashutosh; Saha, Jayanta; Sahoo, Jayanti; Sampath, Prakash; Savith, A.; Shah, Mihir; Shanmugam, Latha; Sharma, Rajeev; Sharma, Priyanka; Sharma, Deepak; Singh, Anit; Singh, Jasdeep; Singh, Prateek; Sivaprakasam, S.; Subramaniam, Suresh; Sudheer, D.; Tandon, Surabhi; Tariq, Muhammad; Tripathi, Vishakha; Vable, M.; Verma, Rahul J; Waghmare, S. P.

doi:10.1016/s0140-6736(21)02000-6

Cited by 297 publications

(235 citation statements)

References 22 publications

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“…BBV152 (Bharat Biotech, Hyderabad, India) is a whole-virion ß-propiolactone-inactivated SARS-CoV-2 vaccine. Efficacy rate of Covaxin was recorded as 77.8% against symptomatic COVID-19 disease after 14 days of two doses ( 9 ). AZD1222 was co-invented by the University of Oxford and its spin-out company, Vaccitech.…”

Section: Introductionmentioning

confidence: 99%

Persistence of Antibodies Against Spike Glycoprotein of SARS-CoV-2 in Healthcare Workers Post Double Dose of BBV-152 and AZD1222 Vaccines

et al. 2021

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Purpose: We investigated the persistence of the vaccine-induced immunoglobulin G (IgG) antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among healthcare workers (HCWs) in Odisha who received a complete dose of either Covaxin or Covishield vaccine.Methods: This 24-week longitudinal cohort study was conducted from January to July 2021 with participants from 6 healthcare and research facilities of Odisha to understand the dynamicity of the vaccine-induced IgG antibodies against SARS-CoV-2 after the complete dose of vaccines.Results: Serum samples were collected from 614 participants during each follow-up and were tested in two chemiluminescent microparticle immunoassay (CLIA)-based platforms to detect SARS-CoV-2 antibodies both qualitatively and quantitatively. Among these participants, 308 (50.2%) participants were Covishield recipients and the rest 306 (49.8%) participants took Covaxin. A total of 81 breakthrough cases were recorded and the rest 533 HCWs without any history of postvaccination infection showed significant antibody waning either from T3 (Covaxin recipient) or T4 (Covishield recipient). The production of vaccine-induced IgG antibodies is significantly higher (p < 0.001) in Covishield compared with Covaxin. Covishield recipients produced higher median anti-S IgG titer than Covaxin. No statistically significant differences in antibody titers were observed based on age, gender, comorbidities, and blood groups.Conclusion: This 6-month follow-up study documents a 2-fold and 4-fold decrease in spike antibody titer among Covishield and Covaxin recipients, respectively. The clinical implications of antibody waning after vaccination are not well understood. It also highlights the need for further data to understand the long-term persistence of vaccine-induced antibody and threshold antibody titer required for protection against reinfection.

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Section: Introductionmentioning

confidence: 99%

Persistence of Antibodies Against Spike Glycoprotein of SARS-CoV-2 in Healthcare Workers Post Double Dose of BBV-152 and AZD1222 Vaccines

et al. 2021

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“…These findings clearly establish that the vaccine-induced T cells are capable of mediating protective response to SARS-CoV-2 variants. The protective contribution of the vaccine-induced T cells is further supported by the phase 3 effectiveness data that shows clinically significant protection from the asymptomatic infection and significantly lower viral load in the delta positive vaccine recipients as compared to the placebo group 3 . Thus, the data reported here provides an understanding on the immunological basis of vaccine effectiveness.…”

Section: Discussionmentioning

confidence: 84%

“…Almost everyone seroconverted after 4-weeks of complete vaccination 2 . Recently reported phase 3 data indicated an efficacy up to 78% against symptomatic infection, 93.4% from severe disease and 63.6% from asymptomatic disease 3 . Despite the global distribution and potential in providing clinically significant protection, limited evidence is available on the mechanism of immunity and the traits of immune memory established by BBV152.…”

Section: Main Textmentioning

confidence: 99%

Inactivated virus vaccine BBV152/Covaxin elicits robust cellular immune memory to SARS-CoV-2 and variants of concern

Vikkurthi

Ansari

Pai

et al. 2021

Preprint

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The characteristics of immune memory established in response to inactivated SARS-CoV-2 vaccines remains unclear. We determined the magnitude, quality and persistence of cellular and humoral memory responses up to 6 months after vaccination with BBV152/Covaxin. Here, we show that the quantity of vaccine-induced spike- and nucleoprotein-antibodies is comparable to that following natural infection and the antibodies are detectable up to 6 months. The RBD-specific antibodies decline in the range of 3 to 10-fold against the SARS-CoV-2 variants in the order of alpha (B.1.1.7) > delta (B.1.617.2) > beta (B.1.351), with no observed impact of gamma (P.1) and kappa (B.1.617.1) variant. We found that the vaccine induces memory B cells, similar to natural infection, which are impacted by virus variants in the same order as antibodies. The vaccine further induced antigen-specific functionally potent multi-cytokine expressing CD4+ T cells in ∼85% of the subjects, targeting spike and nucleoprotein of SARS-CoV-2. Marginal ∼1.3 fold-reduction was observed in vaccine-induced CD4+ T cells against the beta variant, with no significant impact of the alpha and the delta variants. The antigen-specific CD4+ T cells were populated in the central memory compartment and persisted up to 6 months of vaccination. Importantly the vaccine generated Tfh cells that are endowed with B cell help potential, similar to the Tfh cells induced after natural infection. Altogether, these findings establish that the inactivated virus vaccine BBV152 induces robust immune memory to SARS-CoV-2 and variants of concern, which persist for at least 6 months after vaccination. This study provides insight into the attributes of BBV152-elicited immune memory, and has implication for future vaccine development, guidance for use of inactivated virus vaccine, and booster immunization.

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“…The complete series is with 2 doses administered, 4 weeks apart. The phase 3 trial of BBV152 vaccine conducted within India, reported efficacy of 78% and 93% against symptomatic and severe symptomatic infection (7). Recently, Covaxin has been included in the list for emergency use by World Health Organization (8).…”

Section: Introductionmentioning

confidence: 99%

Effectiveness of BBV152 vaccine against SARS-CoV-2 infections, hospitalizations and deaths among healthcare workers in the setting of high delta variant transmission in New Delhi, India

Malhotra

Kalaivani

Lodha

et al. 2022

Preprint

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Background: Delta variant transmission resulted in a surge of SARS CoV-2 cases in New Delhi, India during the early half of the year 2021. Health Care Workers (HCWs) received vaccines on priority for the prevention of infection. The real-life effectiveness of the BBV152 vaccine against severe disease including hospitalization and death was not known. Objective: To estimate the effectiveness of BBV152 vaccine among HCWs against SARS CoV-2 infection, hospitalization, or death Design: Observational study Setting: a multi-specialty tertiary care public-funded hospital in New Delhi, India. Participants: 12,237 HCWs Interventions: BBV152 vaccine (Covaxin, Bharat Biotech Limited, Hyderabad, India); whole virion inactivated vaccine; two doses four weeks apart Measurements: vaccine effectiveness after receipt of two doses of BBV152 protecting against any SARS CoV-2 infection, symptomatic infections or hospitalizations or deaths, and hospitalizations or deaths. Results: The mean age of HCWs was 36(11) years, 66% were men and 16% had comorbidity. After adjusting for potential covariates viz age, sex, health worker type category, body mass index, and comorbidity, the vaccine effectiveness (95% Confidence Interval) in fully vaccinated HCWs and two weeks elapsed after the receipt of the second dose was 44% (37 to 51, p<0.001) against symptomatic infection, hospitalization or death due to SARS CoV-2, and 61% (37 to 76, p<0.001) against hospitalization or death, respectively. Conclusions: BBV152 vaccine with complete two doses offers a modest response to SARS CoV-2 infection in real-life situations against a backdrop of high delta variant community transmission. Efforts in maximizing receipt of full vaccines should be invested for HCWs, who are at higher occupational risk for infection.

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Efficacy, safety, and lot-to-lot immunogenicity of an inactivated SARS-CoV-2 vaccine (BBV152): interim results of a randomised, double-blind, controlled, phase 3 trial

Cited by 297 publications

References 22 publications

Persistence of Antibodies Against Spike Glycoprotein of SARS-CoV-2 in Healthcare Workers Post Double Dose of BBV-152 and AZD1222 Vaccines

Persistence of Antibodies Against Spike Glycoprotein of SARS-CoV-2 in Healthcare Workers Post Double Dose of BBV-152 and AZD1222 Vaccines

Inactivated virus vaccine BBV152/Covaxin elicits robust cellular immune memory to SARS-CoV-2 and variants of concern

Effectiveness of BBV152 vaccine against SARS-CoV-2 infections, hospitalizations and deaths among healthcare workers in the setting of high delta variant transmission in New Delhi, India

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