First Real-World Study Reports Effectiveness of BBV152, a COVID-19 Vaccine Developed in India

The study includes more than 2,700 health professionals in Delhi, India, who were symptomatic and undergoing RT-PCR testing for COVID-19. Findings suggest 50% vaccine effectiveness against symptomatic COVID-19 after two doses of BBV152. This vaccine effectiveness is lower than the vaccine effectiveness suggested by the results of Bharat Biotech’s Phase 3 randomized control study. The authors note several reasons for this difference, including the fact that the delta variant increased significantly in India during the study period (April 15 – May 15, 2021) and this study population consisted of health professionals who were likely more exposed to COVID-19. This study assessed only symptomatic COVID-19 infections and further research is needed to determine the effectiveness of the BBV152 vaccine against hospitalization, serious illness and death.

The first real-world assessment of BBV152, a COVID-19 vaccine developed in India, suggests that two vaccine doses result in 50% effectiveness against symptomatic COVID-19.

The study, published in the journal The Lancet Infectious Diseases, assessed 2,714 hospital workers at the All India Institute of Medical Sciences (AIIMS) in Delhi, India, from April 15 to May 15, 2021, who were symptomatic and undergoing RT-PCR testing for COVID-19. The delta variant was the dominant strain in India during the study period, accounting for approximately 80% of all confirmed COVID-19 cases.[1]

BBV152, developed by Bharat Biotech (India), is a Vero cell-derived, inactivated, whole virion vaccine formulated with a novel adjuvant and administered in a two-dose regimen 28 days apart.

In January 2021, BBV152 was approved for emergency use in India for people aged 18 and over. The World Health Organization (WHO) added BBV152 to its list of approved COVID-19 emergency vaccines in November 2021.[2]

This new study was conducted during the second wave of COVID-19 in India in a high-exposure population (healthcare workers) mainly presented with the BBV152 vaccine, thus providing a unique opportunity to evaluate its effectiveness in the field.

“Our study provides a more complete picture of how BBV152 performs in the field and should be considered in the context of the COVID-19 wave conditions in India, combined with the potential immune evasive potential of the delta variant. Our findings add to the growing body of evidence that rapid vaccine deployment programs remain the most promising path to pandemic control, while public health policies should continue to include additional protective measures such as mask-wearing and social distancing,” said Dr. Manish Soneja, Additional Professor of Medicine at AIIMS in New Delhi.[3]

The study was conducted at AIIMS, a tertiary care hospital and treatment center for COVID-19. Excluding the hospital’s COVID-19 vaccination center

offered BBV152 to all of its 23,000 employees from January 16, 2021. Researchers conducted a test-negative control study between April 15 and May 15, 2021 to evaluate the effectiveness of the BBV152 vaccine against symptomatic RT-PCR-confirmed SARS-CoV-2 infection.

Of the 2,714 employees in the study population, 1,617 people tested positive for SARS-CoV-2 infection and 1097 tested negative. Positive cases were compared to negative RT-PCR tests (controls) using a 1:1 ratio based on age and sex. The probabilities of vaccination with BBV152 were compared between cases and controls and adjusted for occupational exposure to COVID-19, previous SARS-CoV-2 infection and infection dates.

The adjusted vaccine effectiveness against symptomatic COVID-19 after two doses of BBV152, with the second dose administered 14 or more days before the RT-PCR test, was 50% (Figure 3). The effectiveness of two vaccine doses remained stable over the seven-week follow-up period.

The majority of eligible participants were tested for SARS-CoV-2 infection during the first 20 days of the 30-day study, when the test positivity rate for COVID-19 was at its peak in India. At the end of the study period (from May 6 to May 15), the requests for testing gradually decreased. The median interval between receiving the last vaccine dose and the end of the study period (May 15, 2021) for those who received one dose was 37 days (range 7 to 119) days and 50 days (range 5 to 103) days for those who received a single dose. had received two doses. The adjusted vaccine efficacy of the first dose, estimated at 7 and 21 days, was low, which is consistent with the performance of other vaccines against the delta variant and indicates the importance of a second dose to achieve vaccine efficacy.

“Findings of the study confirm previous research indicating that two doses of BBV152 are needed to achieve maximum protection and that all vaccine rollout plans should follow the recommended dosing schedule. More research is needed to better understand how these findings translate into the efficacy of BBV152 against delta and other variants of concern, particularly in relation to severe COVID-19 infection, hospitalization and deaths,” said Dr. Parul Kodan, assistant professor of medicine at AIIMS in New Delhi.[3]

An essential part of any vaccine rollout plan is a post-licensing assessment of the vaccine’s effectiveness in a field setting, as field performance can often differ from controlled trial conditions. Indeed, the authors acknowledge that the effectiveness of the vaccine estimated in this study is lower than the effectiveness reported by a recently published phase 3 randomized control study of BBV152.[4]

The authors note that several factors may be responsible for the lower vaccine effectiveness in this study. First, this study population only included hospital workers who may have a higher risk of exposure to COVID-19 infection than the general population. Second, the study was conducted during the peak of India’s second wave of COVID-19 with high test positivity rates for both hospital workers and Delhi residents. Third, the prevalence of circulating variants of concern, especially delta, may have contributed to the lower effectiveness of BBV152.

The authors acknowledge several limitations in the study. Most importantly, this study does not estimate the vaccine’s effectiveness against hospitalization, serious illness and death, which require further assessment. In addition, the study was not designed to estimate vaccine efficacy for different time intervals after vaccination or to determine whether vaccine efficacy changed over time. Another limitation was the lack of data on co-morbidities and previous COVID-19 infection, which could affect health-seeking behavior and vaccine effectiveness. Although the study took place during the emergence of the delta variant, RT-PCR positive patients were not tested for SARS-CoV-2 variants. Therefore, the authors were unable to definitively estimate the effectiveness of the vaccine against symptomatic COVID-19 due to a specific variant. Future studies should investigate the escape potential of the delta variant.

“Our study took place when the positivity rate of the COVID-19 test in Delhi was around 35% – the highest since the start of the pandemic. It is an important factor to consider when interpreting the impact of a vaccine. Availability of a safe and effective vaccine, addressing hesitant vaccines to achieve proper pace and coverage are the cornerstone of a successful universal vaccination program,” said Professor Naveet Wig, chief of medicine at AIIMS, New Delhi.[3]

dr. Ramachandran Thiruvengadam, Dr. Akshay Binayke and Dr. Amit Awasthi of the Translational Health Science and Technology Institute (India), who was not involved in the study, write in a linked comment: “The decline in vaccine effectiveness against SARS-CoV-2 infection during a delta-driven rise in cases is not surprising or exclusive to inactivated SARS-CoV-2 vaccines, including BBV152. The delta variant has high transmissibility, infectivity and virulence, causing severe disease.These characteristics may have contributed to reduced vaccine efficacy against symptomatic infections, which has been reported to be only 56% for other vaccines in multiple studies around the world… Future studies should be designed with an emphasis on evaluating protection against moderate to severe COVID -19… Nevertheless, Faced with the challenge of protecting as much of the population as possible, the ongoing vaccination campaign must be and continued as a public health intervention against SARS-CoV-2, along with strict adherence to other non-pharmacological interventions, particularly in the context of variant-driven spikes.”

Remarks:

India COVID-19 genome surveillance: https://clingen.igib.res.in/covid19genomes/ The World Health Organization: https://www.who.int/news/item/03-11-2021-who-issues- emergency- use-list-for-eighth-covid-19-vaccine Quote directly from author and cannot be found in the text of the article. The Lancet: Efficacy, safety and lot-to-lot immunogenicity of an inactivated SARS-CoV-2 vaccine (BBV152): interim results from a randomized, double-blind, controlled phase 3 study

Reference: “Effectiveness of an inactivated virus-based SARS-CoV-2 vaccine, BBV152, in India: a test-negative, case-control study” 23 Nov 2021, The Lancet Infectious Diseases.
DOI: 10.1016/S1473-3099 (21) 00674-5