lancet-header

Preprints with The Lancet is part of SSRN´s First Look, a place where journals identify content of interest prior to publication. Authors have opted in at submission to The Lancet family of journals to post their preprints on Preprints with The Lancet. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early stage research papers that have not been peer-reviewed. The findings should not be used for clinical or public health decision making and should not be presented to a lay audience without highlighting that they are preliminary and have not been peer-reviewed. For more information on this collaboration, see the comments published in The Lancet about the trial period, and our decision to make this a permanent offering, or visit The Lancet´s FAQ page, and for any feedback please contact preprints@lancet.com.

Immunogenicity and Tolerability of BBV154 (iNCOVACC®), an Intranasal SARS-CoV-2 Vaccine, Compared with Intramuscular Covaxin® in Healthy Adults: A Randomised, Open-Label, Phase 3 Clinical Trial

33 Pages Posted: 31 Jan 2023

See all articles by Chandramani Singh

Chandramani Singh

All India Institute of Medical Sciences (AIIMS), Bhopal

Savita Verma

Pt. B.D. Sharma Postgraduate Institute of Medical Sciences

Prabhakar Reddy

Nizams Institute of Medical Sciences

Michael S. Diamond

Washington University School of Medicine - Department of Medicine

David T. Curiel

Washington University in St. Louis - Department of Radiation Oncology

Chintan Patel

Aatman Hospital

Manish Kumar Jain

Maharaja Agrasen Super Speciality Hospital

Sagar Vivek Redkar

Redkar Hospital and Research Centre

Amit Suresh Bhate

Jeevan Rekha Hospital

Vivek Gundappa

Rajarajeswari Medical College and Hospital

Rambabu Konatham

Visakha Institute of Medical Science

Leelabati Toppo

Malla Reddy Narayana Multispeciality Hospital

Aniket Chandrakant Joshi

ONP Hospitals

Jitendra Singh Kushwah

Prakhar Hospital

Ajit Pratap Singh

Rana Hospital

Shilpa Gaidhane

Acharya Vinoba Bhave Rural Hospital

Krishna Mohan Vadrevu

Bharat Biotech International Ltd

BBV154 Study Group

Independent

More...

Abstract

Background: Unlike intramuscular vaccines, intranasal COVID-19 vaccines may generate mucosal immunity, which may be critical for to prevent infection and human-to-human transmission. We report interim immunogenicity and safety of an intranasal adenoviral vectored SARS-CoV-2 vaccine (BBV154, iNCOVACC®) in healthy adults compared with licensed intramuscular vaccine (Covaxin®).

Methods: In this open-label, multicentre, phase 3 clinical trial, healthy Indian adults were randomised to receive either two doses of BBV154 (n = 3,000) or Covaxin® (n = 160) 28 days apart. Primary immunogenicity outcome was geometric mean neutralisation antibody titres (PRNT50) against SARS-CoV-2 viruses; key secondary outcomes were safety and solicited adverse events, secretory-IgA and serum-IgA responses and cell-mediated immune responses.

Findings:We screened 3,209 volunteers between April 16 and June 4, 2022 and enrolled and randomised 3,160 to receive BBV154 (n = 2998) or Covaxin (n = 162). On Day 42, 14 days after the second dose, serum GMTs against ancestral (Wuhan) SARS-CoV-2 were 769 (95% CI: 665‒888) and 531 (426‒662) in BBV154 and Covaxin groups. The GMT ratio of 1·45 (95% CI: 1·11‒1·88) met the pre-defined superiority criterion for BBV154 over Covaxin. BBV154 also elicited a higher serum neutralising GMT [171 (137–213)] against Omicron BA.5 than Covaxin [82·4 (48·9–139)]. Similarly, at day 42 GMTs of secretory IgA were 12·3 (95% CI: 8·7 ‒17·4) and 6·6 (95% CI 4·6 ‒9·5) after BBV154 and Covaxin; BBV154 was superior to Covaxin with a GMT ratio of 1·9 (95% CI 1·1–3·0). BBV154 induced higher serum IgA titres and significantly higher levels of antibody-secreting plasmablasts on Day 42. Both vaccines induced equivalent T cell memory responses. Both vaccines were well tolerated, systemic adverse events were reported by 2·7% (82/2990) of BBV154 recipients and 6·2% (10/161) of Covaxin vaccinees. Nasal reactions were experienced by 4·9% (146/2990) of BBV154 participants, whereas 23·0% (37/161) of Covaxin® vaccinees experienced local injection site reactions.

Interpretation:Two intranasal doses of BBV154 were well tolerated with no safety concerns while eliciting superior humoral and mucosal immune responses compared with two intramuscular Covaxin injections. Further studies to assess the effect of BBV154 on infection and transmission are warranted.

Trial Registration: The trial was registered on the Indian Clinical Trials Registry India, CTRI/2022/02/40065, and ClinicalTrials.gov, NCT05522335.

Funding: This work was co-funded by the Biotechnology Industry Research Assistance Council (BIRAC), Department of Biotechnology, Government of India. BT/CS0019/CS/01/20 Dt.12.04.2021, and Bharat Biotech.

Declaration of Interests: BG, SRe, RS, KS, RE, SPr, and KMV are employees of Bharat Biotech, with no stock options or incentives. KE is the Chairman and Managing Director of Bharat Biotech. The principal investigators were CB, MKJ, SVR, ASB, SV, VR, LT, ACJ, CS, JSK, APS, PR, and SB. M.S.D. is a consultant for Inbios, Vir Biotechnology, Senda Biosciences, Moderna, and Immunome. The Diamond laboratory has received unrelated funding support in sponsored research agreements from Vir Biotechnology, Emergent BioSolutions, and Moderna. M.S.D. and Washington University School of Medicine developed the SARS-CoV-2 ChAd vaccine that was licensed to Bharat Biotech for commercial development, and as such could receive royalty payments.

Ethics Approval: The study protocol was approved by the National Regulatory Authority (India) and the respective Ethics Committees at each hospital centre.

Keywords: SARS-COV-2, COVID-19, vaccine, intranasal, intramuscular, immunogenicity, reactogenicity

Suggested Citation

Singh, Chandramani and Verma, Savita and Reddy, Prabhakar and Diamond, Michael S. and Curiel, David T. and Patel, Chintan and Jain, Manish Kumar and Redkar, Sagar Vivek and Bhate, Amit Suresh and Gundappa, Vivek and Konatham, Rambabu and Toppo, Leelabati and Joshi, Aniket Chandrakant and Kushwah, Jitendra Singh and Singh, Ajit Pratap and Gaidhane, Shilpa and Vadrevu, Krishna Mohan and Group, BBV154 Study, Immunogenicity and Tolerability of BBV154 (iNCOVACC®), an Intranasal SARS-CoV-2 Vaccine, Compared with Intramuscular Covaxin® in Healthy Adults: A Randomised, Open-Label, Phase 3 Clinical Trial. Available at SSRN: https://ssrn.com/abstract=4342771 or http://dx.doi.org/10.2139/ssrn.4342771

Chandramani Singh

All India Institute of Medical Sciences (AIIMS), Bhopal ( email )

Bhopal
India

Savita Verma

Pt. B.D. Sharma Postgraduate Institute of Medical Sciences ( email )

Prabhakar Reddy

Nizams Institute of Medical Sciences ( email )

Michael S. Diamond

Washington University School of Medicine - Department of Medicine ( email )

St. Louis, MO 63110
United States

David T. Curiel

Washington University in St. Louis - Department of Radiation Oncology ( email )

Chintan Patel

Aatman Hospital ( email )

Manish Kumar Jain

Maharaja Agrasen Super Speciality Hospital ( email )

Sagar Vivek Redkar

Redkar Hospital and Research Centre ( email )

Amit Suresh Bhate

Jeevan Rekha Hospital ( email )

Vivek Gundappa

Rajarajeswari Medical College and Hospital ( email )

Rambabu Konatham

Visakha Institute of Medical Science ( email )

Leelabati Toppo

Malla Reddy Narayana Multispeciality Hospital ( email )

Aniket Chandrakant Joshi

ONP Hospitals ( email )

Jitendra Singh Kushwah

Prakhar Hospital ( email )

Ajit Pratap Singh

Rana Hospital ( email )

Shilpa Gaidhane

Acharya Vinoba Bhave Rural Hospital ( email )

Krishna Mohan Vadrevu (Contact Author)

Bharat Biotech International Ltd ( email )

India

BBV154 Study Group

Independent

Click here to go to TheLancet.com

Paper statistics

Downloads
1,504
Abstract Views
8,561
PlumX Metrics