Valneva’s inactivated COVID-19 vaccine candidate enters Phase 1/2 clinical trial
Valneva’s candidate is the only inactivated virus vaccine approach being advanced in Europe and the US. Valneva highlights that an inactivated vaccine candidate has the potential to be used in certain vulnerable patient populations; whereas vaccines using new tech are not being administered to such groups because of lack of data. And it says the reduced distribution complexity is another advantage of inactivated vaccines.
Existing manufacturing platform
Valneva’s vaccine candidate, VLA2001, uses the French company’s existing Japanese encephalitis vaccine manufacturing platform (the vaccine, Ixiaro, was approved in 2009 in the US and is also EMA approved).
It contains two adjuvants, alum and CpG 1018, a combination that has ‘consistently induced higher antibody levels in preclinical experiments than alum-only formulations’.
The Phase 1/2 study, VLA2001-201, is a randomized, double blind trial evaluating the safety and immunogenicity for three dose levels in 150 healthy adults in the UK, and is supported by the National Institute for Health Research (NIHR).
The primary endpoint read-out will be two weeks after completion of the two-dose primary immunization (day 0, 21). Subject to analysis of this data, including the selection of the optimal dose (currently expected in the early second quarter of 2021), additional trials are expected to commence immediately afterwards.
VLA2001 consists of inactivated whole virus particles of SARS-CoV-2 with high S-protein density, in combination with two adjuvants, alum and CpG 1018 (CpG 1018 is a component of the US FDA-approved HEPLISAV-B vaccine).
It is produced on Valneva’s established Vero-cell platform, leveraging the manufacturing technology for Valneva’s licensed Japanese Encephalitis Vaccine, IXIARO.
The process includes inactivation with BPL to preserve the native structure of the S-protein.
Why choose an inactivated vaccine candidate?
Front-runners in COVID-19 vaccine development include mRNA-based vaccines from Pfizer and Moderna; as well as viral-vector vaccines from Johnson & Johnson and AstraZeneca. These use new technologies in an effort to create vaccines that can be manufactured quickly and at scale.
Inactivated vaccines, meanwhile, use technology that has been around for decades. They contain viruses treated with heat, chemicals or radiation, so they cannot replicate, but can still trigger an immune response.
As well as using a tried and tested approach, Valneva says inactivated vaccines could prove to help people with weakened immune systems who are at greatest risk: population groups that newer vaccines do not yet have much data on. This includes pregnant women, the elderly and certain immunocompromised patients (the UK’s Joint Committee on Vaccination and Immunisation, for example, says pregnant women or those planning to become pregnant should not receive vaccination at this point in time).
“Inactivated vaccine approaches are historically among the safest and most effective vaccine development strategies, with billions having been vaccinated with this technology over the past century,” a Valneva spokesperson told this publication.
"These include those with weakened immune systems who are at the greatest risk of COVID-19 infection. We believe having an inactivated vaccine that can be used widely and in those at the greatest risk of COVID-19 makes this approach most appropriate. Additionally, having an inactivated vaccine that has a longer shelf life that does not require special shipping or storing requirements is also optimal to reach all those in need of protection.”
Other inactivated COVID-19 vaccines include candidates from Sinovac and Sinopharm (China) and Bharat BioTech (India): which are all in Phase 3 trials.
There are also a number of other inactivated candidates in earlier stage and pre-clinical trials.
UK focus
Earlier this year Valneva announced a major COVID-19 vaccine partnership with the UK government. If it gains regulatory approval, Valneva will supply the UK with 60 million doses in the second half of 2021 with options for the provision of a further 130 million doses across 2022-2025. The partnership also includes UK government investment in Valneva’s Scottish manufacturing facility in Livingston.
The manufacturing process has already been upscaled to final industrial scale; and the vaccine is expected to conform with standard cold chain requirements (2 – 8 degrees centigrade).
“The facility in Livingston, Scotland has been producing FDA/EMA/MHRA approved commercial-grade travel vaccines for more than a decade and it will be the production hub for Valneva’s COVID-19 vaccine candidate," says Valneva.
"This government funding will allow Valneva to expand the site’s capacity for drug substance production and accelerate clinical development. Valneva is committed to making a major contribution to the global need for a COVID-19 vaccine and is in discussions with additional potential governments.
“Valneva’s track-record and capability underpins this partnership. The team is working tirelessly to develop a safe and effective vaccine based on Valneva’s proven and well-established inactivated vaccine approach. With manufacturing and supply chains well-established, Valneva’s long-standing experience in industrial operations can be easily transferred to VLA2001. Valneva has significant expertise in global distribution of vaccines that need standard cold-chain storage. VLA2001 likely requires standard cold chain (2 to 8°C) storage, meaning there is no need for specialized distribution channels, in addition to reduced deployment complexity and cost.”
