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Pandemic Journal

Dr Robert Hess: Second attempt for CureVac: Modified vaccine developed

Dr Robert HEss

Dr Robert Hess – 09/08/2021

Dr Robert Hess: Second attempt for CureVac: Modified vaccine developed in collaboration with GSK is in preclinical testing.

CureVac’s first-generation vaccine candidate CVnCoV unfortunately fell by the wayside in mid-June after failing to meet the statistical criteria for success, but there is now news regarding a modified second-generation vaccine candidate, which CureVac has developed in collaboration with British pharmaceutical giant GSK.

Back in February of this year, CureVac and GSK announced a €150 million joint project with the primary objective of developing multivalent vaccine candidates against viral variants. The initial preclinical data for the second-generation vaccine candidate, CV2CoV, was published in May, with the prospect of clinical trials commencing in the third quarter of this year. However, this target was missed, and the data from the preclinical study in non-human primates did not become available until 16th August 2021.

This study compared the immune response and protective efficacy of the first- and second-generation vaccine candidates. The second-generation CV2CoV was found to activate the innate and adaptive immune response better than its first-generation predecessor at the same dose, resulting in a faster onset of immune response, higher antibody titers and stronger activation of memory B and T cells. In addition, CV2CoV achieves greater antibody neutralization of all selected virus variants, including Beta, Delta and Lambda.

Induction of innate immunity was studied on the basis of specific cytokine markers. Adaptive immune responses were assessed according to specific antibodies for the receptor-binding domain and neutralizing antibodies, as well as memory B and T cells. The current preclinical testing of CV2CoV is to be followed by a phase 1 clinical trial commencing in the fourth quarter of 2021.

What exactly is the difference between the first-generation vaccine candidate (CVnCoV) and the second-generation version (CV2Cov)? CV2CoV is currently in the preclinical development stage and, like CVnCoV, consists of non-chemically modified mRNA which has been encoded for the prefusion-stabilized full-spike protein of the SARS-CoV-2 virus and formulated in lipid nanoparticles (LNPs).

However, CV2CoV is based on a newly developed mRNA “backbone” with specifically optimized non-coding regions to allow improved mRNA translation for enhanced and prolonged protein expression in comparison to that of the first-generation mRNA. The dosage of both vaccine candidates has not changed and remains at 12 µg per vaccine vial.

The data on the new CV2CoV vaccine looks promising so far, and if it carries on in this same positive direction, we expect the vaccine to be available sometime in 2022. We will continue to follow developments closely and provide you with any further information as soon as it becomes available.

Pandemic Journal

CureVac were our great hope

Dr Robert HEss

Dr Robert Hess – 06/23/2021

CureVac was the great hope of Dr Robert Hess. They reached for the stars – and came back down with a bump.

Though the news was not entirely unexpected, we regret to report that the breakthrough vaccine promised by CureVac will now not be forthcoming. There are a number of reasons for this, but the main factor was the high demands that CureVac itself placed on the product. The aim was to develop a vaccine that was as natural as possible – ideally the most natural vaccine to date. In the end, it was the much-debated issue of vaccine-induced side-effects and long-term effects that thwarted their endeavor.

CureVac planned to optimize the “cell packaging” required for transport; this was to avoid having to make chemical changes to the product, as has been the case with vaccines from other manufacturers, in order to increase its tolerability. To fulfill this requirement, CureVac developed a highly natural mRNA-based vaccine. It was a risky strategy and one that ultimately failed, because the chemical-free packaging resulted in greater side-effects. This meant they had to limit the injection dose to 12 micrograms, which reduced the efficacy to just below 50%. By comparison, BioNTech sets its injection dose at 30 micrograms, while the Moderna is more than three times higher at 100.

CureVac also had the ambition to not only produce the most natural vaccine, but also to create one that would be effective against the mutations currently in circulation. With this objective in mind, the clinical phase 3 was delayed in order to include mutation events in the development stage of the product. In comparison to the three market leaders – Moderna, BioNTech and AstraZeneca – who tested only the original Wuhan wild type in their phase 3 trials, CureVac included all subsequent known mutations.

Unfortunately, this set the bar too high. CureVac even attempted to incorporate A.I. (artificial intelligence) into the prediction and detection of future mutations early on and to adapt their product to its findings. Essentially, the project failed because of the as yet insurmountable challenge of developing a natural vaccine that also covers current and even future mutations.

All in all, this is very disappointing news in the context of the pandemic, as governments and health bodies are counting on these next-generation vaccines to deal with future mutations by means of A.I. modeling. In this way, scientists would be able to get ahead of the game and anticipate viral mutations before they manifest themselves. As we have stated in previous Keynotes, we see technology as our only hope of bringing the pandemic under control.

There are other projects going down the same route as CureVac, for example the one at the University of Austin in Texas, but this announcement is still bad news for pandemic management.