Phase III Pivotal comparative clinical trial of intranasal (iNCOVACC) and intramuscular COVID 19 vaccine (Covaxin^®).

"data availability bbv154 a chimpanzee adenoviral-vectored sars-cov-2 intranasal vaccine encoding a prefusion-stabilized spike protein with two proline substitutions in the s2 subunit (genbank: qjq84760"

"Competing interests The principal investigators were C.S., S.V., P.R., C.P., M.K.J., S.V.R., A.S.B., V.G., R.K., L.T., A.C.J., J.S.K., A.P.S. and S.B. B.G., S. Re., K.S., R.E., S. Pr, and K.M.V. are employees of Bharat Biotech, with no stock options or incentives. 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."

"We thank the co-principal investigators, study coordinators and healthcare workers involved in this study. We express our gratitude to Dr. Sivasankar Baalasubramaniam from ImmunitasBio Private Limited, Bangalore, who assisted with cell-mediated response analyses. We appreciate the guidance from Dr. William Blackwelder on sample size estimation and statistical analysis planning. We also thank Dr. Yuvraj Dnyanoba Jogdand, Dr. Amarnath Reddy Kowkuntla, Dr. Vinay Aileni, Dr. Jagadish Kumar and Ms. Sandya Rani, Aparna Bathula and Akhila Kunta of Bharat Biotech, who participated in protocol design and clinical trial monitoring We appreciate the efforts made by Dr. Raju Sunagar, in optimizing the systemic and mucosal IgA analysis. We greatly appreciate the efforts of Dr. Raju Dugyala, Dr. Ramulu Chintala, Ms. Usha Praturi, Dr. Soumya Neelagiri, Dr. Ajay Pathak, Dr. Krishna Shilpa Palem, Ishani Lahiri, Niharika Pentakota and Gayathri Kudupudi in performing serum or saliva binding antibody assays, and PBMCs isolation for cell-mediated assays. This vaccine candidate could not have been developed without the efforts of Bharat Biotech’s Manufacturing and Quality Control teams. Keith Veitch (keithveitch communications, Amsterdam, the Netherlands) provided editorial guidance for the manuscript. Authors acknowledge Biotechnology Industry Research Assistance Council (BIRAC), Department of Biotechnology, Government of India, for providing funding to conduct clinical trial BT/CS0019/CS/01/20 Dt.12.04.2021."

"The study was a randomised, open-label, multicentre trial to evaluate the immunogenicity and safety of BBV154 in healthy adults across 14 hospitals in India. The study protocol was approved by the National Regulatory Authority (India) and the respective Ethics Committees at each hospital centre (see Supplementary Table ). It was registered on the Indian Clinical Trials Registry India, CTRI/2022/02/40065, and ClinicalTrials.gov: identifier, NCT05522335. The trial was conducted in compliance with all International Council for Harmonisation (ICH) Good Clinical Practice guidelines. The objective was to assess and compare the immunogenicity and tolerability of the intranasal vaccine with the licensed intramuscular vaccine, Covaxin."