Selection of optimum formulation of RBD-based protein sub-unit covid19 vaccine (Corbevax) based on safety and immunogenicity in an open-label, randomized Phase-1 and 2 clinical studies

Thuluva, Subhash; Paradkar, Vikram; Turaga, Kishore; Gunneri, SubbaReddy; Yerroju, Vijay; Mogulla, Rammohan; Kyasani, Mahesh; Manoharan, Senthil Kumar; Medigeshi, Guruprasad R.; Singh, Janmejay; Shaman, Heena; Singh, Chandramani; Rao, Angoori Gnaneshwar

doi:10.1101/2022.03.08.22271822

Cited by 12 publications

(16 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, we also evaluated the option to prime the mice with RBD/alum+CpG and boost with RBD/alum alone. This formulation is equivalent to the Corbevax TM vaccine that recently received emergency use authorization by the Drugs Controller General of India [25].…”

Section: Introductionmentioning

confidence: 99%

Receptor-binding domain recombinant protein on alum-CpG induces broad protection against SARS-CoV-2 variants of concern

Pollet

Strych

Chen

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

We conducted preclinical studies in mice using a yeast-produced SARS-CoV-2 RBD219-N1C1 subunit vaccine candidate formulated with aluminum hydroxide (alum) and CpG deoxynucleotides. This vaccine formulation is similar to one that entered advanced phase 3 clinical development in India. We compared the immune response of mice vaccinated with RBD219-N1C1/alum to mice vaccinated with RBD219-N1C1/alum+CpG. We also evaluated mice immunized with RBD219-N1C1/alum+CpG and boosted with RBD219-N1C1/alum. Mice were immunized twice intramuscularly at a 21-day interval. Compared to two doses of the RBD219-N1C1/alum formulation, the RBD219-N1C1/alum+CpG vaccine induced a stronger and more balanced Th1/Th2 cellular immune response, with high levels of neutralizing antibodies against the original Wuhan isolate of SARS-CoV-2 as well as the B.1.1.7 (Alpha), B.1.351 (Beta) and B.1.617.1 (Kappa) variants. Notably, the sera from mice that received two 7 μg doses of RBD219-N1C1/alum+CpG showed more than 18 times higher neutralizing antibody titers against B.1.351, than the WHO International Standard for anti-SARS-CoV-2 immunoglobulin NIBSC 20/136. Interestingly, a booster dose did not require the addition of CpG to induce this effect. The data reported here reinforces that the RBD219-N1C1/alum+CpG vaccine formulation is suitable for inducing broadly neutralizing antibodies against SARS-CoV-2 including three variants of concern, B.1.1.7 (Alpha), B.1.351 (Beta), and B.1.617.1 (Kappa).

show abstract

Section: Introductionmentioning

confidence: 99%

Receptor-binding domain recombinant protein on alum-CpG induces broad protection against SARS-CoV-2 variants of concern

Pollet

Strych

Chen

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, it is worth noting that in a small set of patients (n=360) safety was established until 12 months and significantly higher neutralizing antibody titres (nAbs) persisted at least 6 months after second dose of the vaccination when compared to human convalescent serum (HCS). 5 Overall, we conclude that CORBEVAX™ is safe, well tolerated and elicited excellent antibody and cellular immune responses that can offer significant protection against symptomatic infection from SARS-CoV-2 virus.…”

Section: Study Limitationsmentioning

confidence: 67%

Section: Discussionmentioning

confidence: 99%

“…The RBD subunit is coformulated along with aluminum Hydroxide and CpG1018. 5 The active comparator used in immunogenicity arm of the study is COVISHIELD™ (ChAdOx1 nCoV-19) is a Covid-19 vaccine. This vaccine is based on recombinant, replication-deficient chimpanzee adenovirus vector encoding the SARS-CoV-2 Spike (S) glycoprotein, produced in genetically modified human embryonic kidney (HEK) 293 cells (CDSCO.gov).…”

Section: Randomization and Maskingmentioning

confidence: 99%

“…The optimum formulation showed excellent safety profile with minimal reactogenicity and high humoral immune response in terms of anti-RBD IgG titers and neutralizing antibody titers against Ancestral, Beta and Delta strains of SARS-COV-2 as well as desired Th1 skew of the cellular immune response. 5 In the current phase III study using the optimum formulation of CORBEVAX™, we report the safety and immunogenic superiority of CORBEVAX™ vaccine over COVISHIELD™ vaccine.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Immunogenic superiority and safety of Biological E CORBEVAX vaccine compared to COVISHIELD (ChAdOx1 nCoV-19) vaccine studied in a phase III, single blind, multicenter, randomized clinical trial

Thuluva

Paradkar

Turaga

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Background: Optimum formulation of Biological Es CORBEVAX vaccine that contains protein sub unit of Receptor Binding Domain (RBD) from the spike protein of SARS-COV-2 formulated with aluminum hydroxide (Al3+) and CpG1018 as adjuvants was selected in phase-1 and 2 studies and proven to be safe, well tolerated and immunogenic in healthy adult population. In the current study, additional data was generated to determine immunogenic superiority of CORBEVAX vaccine over COVISHIELD vaccine and safety in larger and older population. Methods: This is a phase III prospective, single blinded, randomized, active controlled study (CTRI/2021/08/036074) conducted at 18 sites across India in healthy adults aged between 18-80 years. This study has two arms; immunogenicity arm and safety arm. Participants in immunogenicity arm were randomized equally to either CORBEVAX or COVISHIELD vaccination groups to determine the immunogenic superiority. Healthy adults without a history of Covid-19 vaccination or SARS-CoV-2 infection, were enrolled. Findings: The safety profile of CORBEVAX vaccine was comparable to the comparator vaccine COVISHIELD in terms of overall AE rates, related AE rates and medically attended AEs. Majority of reported AEs were mild in nature, and overall CORBEVAX appeared to cause fewer local and systemic adverse reactions/events. Overall, two grade-3 serious AEs (Dengue fever and femur fracture) were reported and they are unrelated to study vaccine. Neutralizing Antibody titers, against both Ancestral and Delta strain, induced post two-dose vaccination regimen were higher in the CORBEVAX arm as compared to COVISHIELD and the analysis of GMT ratios demonstrated immunogenic superiority of CORBEVAX in comparison with COVISHIELD. Both CORBEVAX and COVISHIELD vaccines showed comparable seroconversion post vaccination when assessed against anti-RBD IgG response. The subjects in CORBEVAX cohort also exhibited higher Interferon-gamma secreting PBMCs post stimulation with SARS-COV-2 RBD peptides than the subjects in COVISHIELD cohort. Interpretations: Neutralizing antibody titers induced by CORBEVAX vaccine against Delta and Ancestral strains were protective, indicative of vaccine effectiveness of >90% for prevention of symptomatic infections based on the Correlates of Protection assessment performed during Moderna and Astra-Zeneca vaccine Phase III studies. Safety findings revealed that CORBEVAX vaccine has excellent safety profile when tested in larger and older population.

show abstract

Recent review of COVID-19 management: diagnosis, treatment and vaccination

et al. 2022

View full text Add to dashboard Cite

The idiopathic Coronavirus disease 2019 (COVID-19) pandemic outbreak caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has reached global proportions; the World Health Organization (WHO) declared it as a public health emergency during the month of January 30, 2020. The major causes of the rise of new variants of SARS-CoV-2 are genetic mutations and recombination. Some of the variants with high infection and transmission rates are termed as variants of concern (VOCs) like currently Omicron variants. Pregnant women, aged people, and immunosuppressed and compromised patients constitute the most susceptible human population to the SARS-CoV-2 infection, especially to the new evolving VOCs. To effectively manage the pathological condition of infection, the focus should be directed towards prevention and prophylactic approach. In this narrative review, we aimed to analyze the current scenario of COVID-19 management and discuss the treatment and prevention strategies. We also focused on the complications prevalent during the COVID-19 and post-COVID period and to discuss the novel approaches developed for mitigation of the global pandemic. We have also emphasized on the COVID-19 management approaches for the special population including children, pregnant women, aged groups, and immunocompromised patients. We conclude that the advancements in therapeutic and pharmacological domains have provided opportunities to develop and design novel diagnosis, treatment, and prevention strategies. New advanced techniques such as RT-LAMP, RT-qPCR, High-Resolution Computed Tomography, etc., efficiently diagnose patients with SARS-CoV-2 infection. In the case of treatment options, new drugs like paxlovid, combinations of β-lactum drugs and molnupiravir are found to be effective against even the new emerging variants. In addition, vaccination is an essential approach to prevent the infection or to reduce its severity. Vaccines for against COVID-19 from Comirnaty by Pfizer-BioNTech, SpikeVax by Moderna, and Vaxzevria by Oxford-AstraZeneca are approved and used widely. Similarly, numerous vaccines have been developed with different percentages of effectiveness against VOCs. New developments like nanotechnology and AI can be beneficial in providing an efficient and reliable solution for the suppression of SARS-CoV-2. Public health concerns can be efficiently treated by a unified scientific approach, public engagement, and better diagnosis.

show abstract

Selection of optimum formulation of RBD-based protein sub-unit covid19 vaccine (Corbevax) based on safety and immunogenicity in an open-label, randomized Phase-1 and 2 clinical studies

Cited by 12 publications

References 27 publications

Receptor-binding domain recombinant protein on alum-CpG induces broad protection against SARS-CoV-2 variants of concern

Receptor-binding domain recombinant protein on alum-CpG induces broad protection against SARS-CoV-2 variants of concern

Immunogenic superiority and safety of Biological E CORBEVAX vaccine compared to COVISHIELD (ChAdOx1 nCoV-19) vaccine studied in a phase III, single blind, multicenter, randomized clinical trial

Recent review of COVID-19 management: diagnosis, treatment and vaccination

Contact Info

Product

Resources

About