How CureVac is creating a ‘broad pipeline’ of both first and second generation COVID-19 vaccines

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Pic:getty/jatuporntansirimas (Getty Images/iStockphoto)

CureVac aims to bring together expertise from both its own company and other stakeholders to provide ‘broader and faster protection against current and future viral threats’: through collaborations with the UK Government, Bayer and GSK.

A collaboration with Bayer will help CureVac scale up production of its Phase 3 candidate, CVnCoV, while a partnership with GSK will allow it to create improved second generation vaccines – such as multivalent vaccines or a vaccine against multiple respiratory diseases.

These will be underpinned by a newly announced R&D partnership with the UK Government, with the UK providing the scientific insight into which strains could become significant in the future.

While CureVac’s current candidate is yet to be authorized, a new first-generation vaccine specifically against the South African variant is already in development and could be rolled out in the fall this year.

Developing mRNA tech

With the technology also used by vaccine frontrunners Pfizer/BioNTech and Moderna, mRNA tech has come to the fore during the coronavirus pandemic.

“mRNA technology has emerged as the key technology to rapidly provide potent, flexible and easy to manufacture vaccines and that – without a doubt – will have a long lasting impact on the way we will globally address and prepare for future pandemics and vaccine development,” said CureVac CEO Dr. Franz-Werner Haason a conference call on Friday.

The first step in creating new mRNA vaccines will be to identify which strains pose the biggest concern and need for a modified vaccine: which a new partnership with the UK Government, announced Friday, will address.

The UK government is forming a new expert advisory group, which investigate both current and potential future virus variants. This will involve using the UK Science Surveillance networks alongside genomic sequencing technologies and clinical trial capabilities to allow the rapid identification of and response to virus variants.

“The scientific insight we will receive through this collaboration will provide a fast-track to select the most relevant mutations for both our first and second generation vaccines,” explained Haas.

This will be used to update the first-generation CVnCoV a similar way to how flu vaccines are updated every year; with the mRNA technology allowing for reformulation more quickly than with traditional vaccine technologies.

The first new vaccine from the partnership, against the South African strain, could become available in the fall of this year: with the UK already placing an initial order for 50 million doses of this vaccine if required. CureVac anticipates new vaccines could be created in a matter of weeks; and it should be possible for new versions of the vaccine to run accelerated clinical trials ahead of regulatory approval.

CureVac is currently in discussions with the MHRA and other regulators as to how authorization for a modified first generation vaccine will be given, said Anthony Blanc, CureVac's Chief Business Officer and Chief Commercial Officer. "In essence, the thinking that is emerging from different authorities in the UK - but also Europe and US - is that it will be more akin to a flu variation, in the way it is done every year, on the back of a relatively small immuno-bridging study."

As part of the UK partnership, CureVac will tech transfer its manufacturing process to enable fast manufacturing in the UK: allowing the country to boost its capacity to develop and manufacture vaccines in the UK.

First and second generation vaccines

CureVac's two other main partnerships are a collaboration and service agreement with fellow German pharmaceutic Bayer on first generation vaccines; and a co-development partnership with GSK on second generation vaccines.

First generations vs second generation vaccines for COVID-19

CureVac’s first generation vaccines will all use the same mRNA backbone as its current CVnCoV candidate. Second generations vaccines, in contrast, will create a new mRNA backbone with improved characteristics, such as low dose immune activation and stability.

“Our first generation vaccines are being developed to tackle the current pandemic starting with a focus on the initially dominant strain of COVID-19. When we say “first generation,” we are referring to vaccines which apply the same mRNA backbone – meaning the same mRNA setup – as our lead vaccine candidate, CVnCoV, which is currently in late-stage Phase2b/3 clinical testing," explained Dr. Franz-Werner Haas.

In using the same mRNA backbone, new CVnCoV versions can be realized within weeks - such as one against the South Africa strain. 

“Our second generation vaccines refer to vaccines applying a new mRNA backbone or setup which differs from the setup of our leading first-generation candidate, CVnCoV, and which is generated on the basis of our learnings from CVnCoV over the past year," said Haas. "The aim of our second generation vaccine program is to further improve on important mRNA characteristics such as protein expression level, low dose immune activation and stability.

"A second generation lead candidate is currently being developed at CureVac and has shown strong pre-clinical potential.

"Both our first and our second generation vaccines are not only geared toward addressing the current pandemic, but are also intended to address both current and future emerging variants. This will allow to cover multiple approaches, including vaccines that address specific mutations and multivalent vaccines, which combine several antigens."

The Bayer partnership focuses on the existing, first generation vaccine: helping CureVac scale up development and manufacture of CVnCoV and new versions of CVnCoV that are designed to address mutations in the SARS-CoV-2 spike protein. This has been designed as a service agreement, with CureVac paying Bayer an unspecified sum.

A €150m (US$180m) partnership with GSK, announced last week, will focus on developing second generation vaccines – those with a different mRNA backbones and improving on the first generation version (whether for the original spike protein or spike protein mutations). This could also include a multivalent vaccine – addressing multiple strains in one vaccine – or vaccines that address multiple respiratory viruses (including COVID-19). GSK and CureVac will share costs and margins from such vaccines. 

The first vaccine from this partnership could become available in 2022, subject to regulatory approval.