Immunogenicity and protective efficacy of inactivated SARS-CoV-2 vaccine candidate, BBV152 in rhesus macaques
Pragya D Yadav, Raches Ella, Sanjay Kumar, Dilip R Patil, Sreelekshmy Mohandas, Anita M Shete, Krishna M Vadrevu, Gaurav Bhati, Gajanan Sapkal, Himanshu Kaushal, Savita Patil, Rajlaxmi Jain, Gururaj Deshpande, Nivedita Gupta, Kshitij Agarwal, Mangesh Gokhale, Basavaraj Mathapati, Siddhanath Metkari, Chandrashekhar Mote, Dimpal Nyayanit, Deepak Y Patil, B S Sai Prasad, Annasaheb Suryawanshi, Manoj Kadam, Abhimanyu Kumar, Sachin Daigude, Sanjay Gopale, Triparna Majumdar, Deepak Mali, Prasad Sarkale, Shreekant Baradkar, Pranita Gawande, Yash Joshi, Sidharam Fulari, Hitesh Dighe, Sharda Sharma, Rashmi Gunjikar, Abhinendra Kumar, Kaumudi Kalele, Vellimedu K Srinivas, Raman R Gangakhedkar, Krishna M Ella, Priya Abraham, Samiran Panda, Balram Bhargava, Pragya D Yadav, Raches Ella, Sanjay Kumar, Dilip R Patil, Sreelekshmy Mohandas, Anita M Shete, Krishna M Vadrevu, Gaurav Bhati, Gajanan Sapkal, Himanshu Kaushal, Savita Patil, Rajlaxmi Jain, Gururaj Deshpande, Nivedita Gupta, Kshitij Agarwal, Mangesh Gokhale, Basavaraj Mathapati, Siddhanath Metkari, Chandrashekhar Mote, Dimpal Nyayanit, Deepak Y Patil, B S Sai Prasad, Annasaheb Suryawanshi, Manoj Kadam, Abhimanyu Kumar, Sachin Daigude, Sanjay Gopale, Triparna Majumdar, Deepak Mali, Prasad Sarkale, Shreekant Baradkar, Pranita Gawande, Yash Joshi, Sidharam Fulari, Hitesh Dighe, Sharda Sharma, Rashmi Gunjikar, Abhinendra Kumar, Kaumudi Kalele, Vellimedu K Srinivas, Raman R Gangakhedkar, Krishna M Ella, Priya Abraham, Samiran Panda, Balram Bhargava
Abstract
The COVID-19 pandemic is a global health crisis that poses a great challenge to the public health system of affected countries. Safe and effective vaccines are needed to overcome this crisis. Here, we develop and assess the protective efficacy and immunogenicity of an inactivated SARS-CoV-2 vaccine in rhesus macaques. Twenty macaques were divided into four groups of five animals each. One group was administered a placebo, while three groups were immunized with three different vaccine candidates of BBV152 at 0 and 14 days. All the macaques were challenged with SARS-CoV-2 fourteen days after the second dose. The protective response was observed with increasing SARS-CoV-2 specific IgG and neutralizing antibody titers from 3rd-week post-immunization. Viral clearance was observed from bronchoalveolar lavage fluid, nasal swab, throat swab and lung tissues at 7 days post-infection in the vaccinated groups. No evidence of pneumonia was observed by histopathological examination in vaccinated groups, unlike the placebo group which exhibited interstitial pneumonia and localization of viral antigen in the alveolar epithelium and macrophages by immunohistochemistry. This vaccine candidate BBV152 has completed Phase I/II (NCT04471519) clinical trials in India and is presently in phase III, data of this study substantiates the immunogenicity and protective efficacy of the vaccine candidates.
Conflict of interest statement
The authors declare no competing interests.
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References
- Wang C, et al. A novel coronavirus outbreak of global health concern. Lancet. 2020;395:470–473. doi: 10.1016/S0140-6736(20)30185-9.
- World Health Organization. WHO coronavirus disease (COVID-19) dashboard. (2020).
- World Health Organization. Module 2: types of vaccine and adverse reactions. (2020).
- Krammer F. SARS-CoV-2 vaccines in development. Nature. 2020;586:516–527. doi: 10.1038/s41586-020-2798-3.
- Wang H, et al. Development of an inactivated vaccine candidate, BBIBP-CorV, with potent protection against SARS-CoV-2. Cell. 2020 doi: 10.1016/j.cell.2020.06.008.
- Gao Q, et al. Development of an inactivated vaccine candidate for SARS-CoV-2. Science. 2020 doi: 10.1126/science.abc1932.
- Ganneru, B. et al. Evaluation of safety and immunogenicity of an adjuvanted, TH-1 skewed, whole virion inactivated SARS-CoV-2 vaccine-BBV152. Preprint at (2020).
- Mohandas, S. et al. Immunogenicity and protective efficacy of BBV152: a whole virion inactivated SARS CoV-2 vaccine in the Syrian hamster model. iScience 102054 10.1016/j.isci.2021.102054 (2021).
- Doremalen N, et al. ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in rhesus macaques. Nature. 2020;30:1–8.
- Mercado NB, et al. Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques. Nature. 2020;30:1–1.
- Corbett KS, et al. Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in nonhuman primates. N. Engl. J. Med. 2020 doi: 10.1056/NEJMoa2024671.
- Patel, A. et al. Intradermal-delivered DNA vaccine provides anamnestic protection in a rhesus macaque SARS-CoV-2 challenge model. Preprint at (2020).
- Annette, B. et al. A prefusion SARS-CoV-2 spike RNA vaccine is highly immunogenic and prevents lung infection in non-human primates. Preprint at (2020).
- US Food and Drug Administration. Pfizer-BioNTech COVID-19 vaccine. (2021).
- Speranza, E. et al. SARS-CoV-2 infection dynamics in lungs of African green monkeys. Cell (2020).
- Alexandersen S, et al. SARS-CoV-2 genomic and subgenomic RNAs in diagnostic samples are not an indicator of active replication. Nat. Commun. 2020;11:6059. doi: 10.1038/s41467-020-19883-7.
- Yang X, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet. Respir. Med. 2020;8:475–481.
- Mazzoni A, et al. Impaired immune cell cytotoxicity in severe COVID-19 is IL-6 dependent. J. Clin. Investig. 2020 doi: 10.1172/JCI138554.
- Chen, Z. & John Wherry, E. T cell responses in patients with COVID-19. Nat. Rev. Immunol. 1–8. 10.1038/s41577-020-0402-6 (2020).
- Chandrashekar A, et al. SARS-CoV-2 infection protects against rechallenge in rhesus macaques. Science. 2020;80:4776.
- Surh CD, Sprent J. Homeostasis of naive and memory T cells. Immunity. 2008;29:848–862. doi: 10.1016/j.immuni.2008.11.002.
- Lindsley AW, et al. Eosinophil responses during COVID-19 infections and coronavirus vaccination. J. Allergy Clin. Immunol. 2020;146:1–7. doi: 10.1016/j.jaci.2020.04.021.
- Committee for the Purpose of Control and Supervision on Experiments on Animals. CPCSEA guidelines for laboratory animal facility. Indian J. Pharmacol.3510.13140/2.1.3877.2802 (2020).
- Sarkale P, et al. First isolation of SARS-CoV-2 from clinical samples in India. Indian J. Med. Res. 2020;151:244–250.
- Potdar V, et al. Genomic analysis of SARS-CoV-2 strains among Indians returning from Italy, Iran & China, & Italian tourists in India. Indian J. Med. Res. 2020;151:255–260.
- Kumar, N. et al. Distribution of the genetic clade “G” of SARS-CoV-2—an insight into COVID-19 virulence and spread in India. 10.35543/ (2020).
- Hadfield, J. et al. Nextstrain: real-time tracking of pathogen evolution. Bioinformatics34, 4121–4123 (2018).
- Mercatelli D, et al. Geographic and genomic distribution of SARS-CoV-2 mutations. Front. Microbiol. 2020;11:1800. doi: 10.3389/fmicb.2020.01800.
- Patil DR, et al. Study of Kyasanur forest disease viremia, antibody kinetics, and virus infection in target organs of Macaca radiata. Sci. Rep. 2020;10:1–3. doi: 10.1038/s41598-019-56847-4.
- Sapkal G, et al. Development of indigenous IgG ELISA for the detection of anti-SARS-CoV-2 IgG. Indian J. Med. Res. 2020;151:444–449. doi: 10.4103/ijmr.IJMR_2232_20.
- Perera RA, et al. Serological assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Eur. Surveill. 2020;25:2000421. doi: 10.2807/1560-7917.ES.2020.25.16.2000421.
- Choudhary ML, et al. Development of in vitro transcribed RNA as positive control for laboratory diagnosis of SARS-CoV-2 in India. Indian J. Med. Res. 2020;151:251–254.
- World Health Organization. Coronavirus Disease (COVID-19) Technical Guidance: Laboratory Testing for 2019-nCoV in Humans. (WHO, 2020).
- Wolfel R, et al. Virological assessment of hospitalized patients with COVID-2019. Nature. 2020;581:465–469. doi: 10.1038/s41586-020-2196-x.
- Kaushal H, et al. Evaluation of cellular immunological responses in mono- and polymorphic clinical forms of post-kala-azar dermal leishmaniasis in India. Clin. Exp. Immunol. 2016;185:50–60. doi: 10.1111/cei.12787.
- Culling, C. F. A. Handbook of Histopathological and Histochemical Techniques: Including Museum Techniques (Butterworth-Heinemann, 2013).
- Schafer KA, et al. Use of severity grades to characterize histopathologic changes. Toxicol. Pathol. 2018;46:256–265. doi: 10.1177/0192623318761348.
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