COVIVAXX

is a RBD VLP Display COVID-19 vaccine candidate

Under development by the Serum Institute of India Pvt. LTD, in collaboration with Vakzine Projekt Management GmbH. 

COVIVAXX

COVIVAXX is a conjugate vaccine designed to generate an immune response against the spike protein of the disease-causing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to protect against COVID-19. The proof-of-concept has been demonstrated in animal studies with a 100% seroconversion and high levels of antibody titres against the receptor-binding domain (RBD) of the spike protein. A phase I/II trial is currently ongoing in Australia to assess the safety and immunogenicity of COVIVAXX in humans. A pivotal phase III trial is planned to be conducted in Europe and India in the first half of 2021. Marketing authorization is aimed to be sought via the European Medicines Agency (EMA) rolling review to ensure swift access for European countries. Other countries worldwide, such as India, will gain access through respective expedited approval procedures.


The vaccine candidate comprises a conjugate of the RBD of the spike protein of SARS-CoV-2 and the established and reliable technology of virus like particles (VLP). In order to achieve enhanced immunogenicity, the Spycatcher-Spytag technology is used, which allows for effective surface presentation of the antigen; a prerequisite for an efficacious SARS-CoV-2 vaccine. The proof-of-concept was already demonstrated for a malarial antigen by inducing a higher antibody response.


The advantage of this platform technology is that the HBsAg Spycatcher component can be produced in the yeast Hansenula polymorpha, while the RBD Spytag component is produced in the yeast Pichia pastoris. The yeast-based production of the components is well-established, reliable and easily scalable.


The resulting VLPs display T cell epitopes and are capable of eliciting efficient TH1 and cytotoxic T lymphocytes (CTL) responses. VLPs have the ability to be cross-presented and to enter the major histocompatibility class I (MHC-I) pathway. This ability is owed to their particulate nature which allows the VLPs to be efficiently taken up by antigen presenting cells (APCs) and enter the MHC-I pathway. VLPs combined with stimuli for APCs are able to induce CTL and TH1 responses.


The immunogenicity of the VLPs is further enhanced by the presence of the aluminum adjuvant. Nonclinical studies demonstrated that pre-existing immunity against the HBsAg is not affecting the immunogenicity of the VLPs.


Serum Institute of India Private Limited (SIIPL), as the globally leading vaccine manufacturer, and Vakzine Projekt Management GmbH (VPM) which sponsors and/or coordinates vaccine trials in Europe and globally, ensure timely large-scale manufacture and distribution of COVIVAXX by meeting the highest quality standards. SIIPL has secured its right to produce and commercialize COVIVAXX in the European Union (EU). SIIPL has facilities, equipment, and experienced staff to produce an annual capacity of 2 billion doses of COVIVAXX by the completion of the planned phase III trial. VPM will assist COVIVAXX’s import into the EU, certification and release by an EU-based qualified person in compliance with the applicable European laws and regulations.



Serum Institute of India: “the capability to service and help the world"

our insight of the week - March 14, 2021
CoviShield, Serum Institute of India's version of AstraZeneka's AZD1222, photo adobe stock
India, with over 10 million confirmed COVID-19 cases, is the second most affected country in the world. So, on January 12th, 2021, when Serum Institute of India (SII) sent out the first shipments of COVISHIELD vaccines to multiple locations across India, it was indeed “an emotional moment” for many, as SII CEO Adar Poonawalla stated on Twitter. 

SII is the world’s largest vaccine manufacturer by number of doses produced – around 1.5 billion each year. Before the coronavirus pandemic, the vaccines manufactured by SII included Polio, Diphtheria, Tetanus, Hepatitis B, Mumps, Rubella and many more. It is estimated that about 65 percent of the children in the world receive at least one vaccine manufactured by SII, the company’s website states. Not just SII as a company, but India as a country is the world’s top vaccine manufacturer. That is why they both play a crucial role in supplying the globe with a vaccine against COVID-19. 

There are three major COVID-19 vaccine candidates in which SII is involved: while the aforementioned COVISHIELD and COVOVAX are both being manufactured by SII, they have been developed by AstraZeneca/Oxford University and Novavax respectively and licensed to the India-based company. The third candidate, COVIVAXX, is being developed by SII themselves, in collaboration with German company Vakzine Projekt Management (VPM). SII has facilities, equipment, and experienced staff to produce an annual capacity of 2 billion doses of COVIVAXX by the completion of the planned phase III trial. VPM will assist COVIVAXX’s certification and release in the EU. 
Serum Institute of India's R&D Director Dr. Umesh Shaligram (standing row, fifth from left) with his team and guests from the European Investment Bank (EIB), photo kENUP Foundation
COVIVAXX’S yeast-based VLP platform is already being used successfully for multiple vaccines produced by Serum Institute in volumes of more than 200 million doses annually. SII’s experience with yeast-based product manufacturing spans more than two decades. Even after the current pandemic is under control, going forward, the platform technology could be kept as a ready-to-use platform should a new epidemic or pandemic situation arise in future.

The start of COVIVAXX’S clinical trial in Europe and India is expected for the second quarter of 2021. Currently, phase I/II clinical trials are already ongoing in Australia and results are expected in March 2021. Due to SII’s experience in vaccine manufacturing, as well as already established technologies and facilities, the company can ensure large-scale manufacture of COVIVAXX that will be affordable for the EU and other countries worldwide.

This is an important point for SII: CEO Poonawalla has emphasized that the company wants its COVID-19 vaccines to be affordable and accessible to all. For COVISHIELD, this means that SII will sell to the government of India at the affordable price of 3 to 4 USD per dose. After supplying India and the GAVI countries, Poonawalla continues in the statement, the private market will open up with prices around 6 to 8 USD per dose. This is still far lower than most other prominent vaccine candidates, the BioNTech/Pfizer vaccine for example costs around 20 USD.
CEO Ada Poonawalla (right) with President Dr. Cyrus Poonawalla (sitting) and members SII's top management
photo kENUP Foundation
Furthermore, SII’s vaccines could be very viable candidates especially for low-and-middle-income countries. The currently developed COVIVAXX only requires normal refrigerator temperatures of 2 to 8 degrees Celsius. The same goes for COVISHIELD, which is already being manufactured and distributed. This makes it a lot easier to transport than some other COVID-19 vaccines that need to be kept at temperatures of up to minus 70 degrees Celsius. Especially in remote and underserved areas or very warm climates, high maintenance of vaccines during transport could become a huge problem for distribution. AstraZeneca and Oxford licensed COVISHIELD to SII on a pledge that it would deliver it to the world’s poorest people at cost. Some of the first doses have been already shipped to Bhutan, Maldives, Bangladesh, Nepal, Myanmar and Seychelles.

SII will also manufacture up to 40 to 50 million doses per month of the COVOVAX vaccine developed by Novavax, starting from around April. As Poonawalla announced on Twitter, he hopes to launch the COVOVAX vaccine by June 2021, having also applied to start local trials in India. The vaccine was found to be 89.3% effective in a UK trial. As of February 5th, 2021, the Central Drugs Standard Control Organisation (CDSCO) of India has permitted SII to conduct a phase 2 and 3 bridging study for Covovax.

In a further effort to fight the pandemic on a global level, SII will supply 1.1 billion doses of COVID-19 vaccines to the COVAX vaccine scheme, an accelerator working for global equitable access to COVID-19 vaccines led by CEPI, GAVI and the WHO. This was announced as part of a new long-term deal on February 3rd. The doses will be delivered over a number of years to low-and-middle-income countries at the cost of around 3 USD per dose. 

“The way the world has looked at India now, it’s been overwhelming because we were always ignored and thought about as backward, in many respects,” SII CEO Poonawalla said in an interview with The New York Times in early January 2021. “The world now has to recognize the capabilities of India to service the world and help the world, and that’s exactly what we’re doing,” he added.


March 14, 2021 by kENUP