Valneva Corona vaccine: EMA recommends approval

Experience with cholera and encephalitis vaccines

Valneva is currently developing vaccines for Lyme disease and the Zika virus, and has already developed vaccines for cholera and Japanese encephalitis. Like these two, the company’s coronavirus vaccine contains complete, inactivated, i.e. non-replicating, viruses. Unlike the Covid-19 vaccines previously approved in Germany, the human immune system produces antibodies not only against the spike protein, but also against other structures in the outer shell of the Sars-CoV-2 coronavirus.

However, vaccination with only inactivated viruses does not usually activate the immune system sufficiently to provide adequate protection against the pathogen. Therefore, whole virus vaccines usually contain so-called adjuvants. Like inactivated pathogens, they are recognized as invaders by the immune system and dealt with. Adjuvants increase the effect but can also cause unpleasant vaccine reactions and side effects.

A vaccine with two potentiators

Valnevy uses two different adjuvants. One adjuvant is aluminum hydroxide, which has been added to vaccines for decades. For example, it is part of the diphtheria and tetanus vaccines. The second adjuvant, CpG 1018, is new. Until now, it was only included in the hepatitis B vaccine. CpG 1018 is a small fragment of synthetically produced DNA. Its structure is similar to the genetic material of bacteria and viruses. The innate immune system recognizes the pattern of this building block of DNA and reacts to it. In particular, CpG 1018 is believed to stimulate the development of a specific subset of T helper cells that are not responsive to aluminum hydroxide.

According to Valneva, fears that a DNA fragment could enter the human genome are unfounded: “Human genomic DNA does not change under any circumstances,” the company replies to BR’s request. The vaccine components only served to stimulate an immune response. Vaccination with VLA2001 is not a gene therapy that replaces, deactivates or repairs human genes.

Dead vaccine or not?

Valnevy vaccine is usually called an inactivated vaccine. This name goes back to a time when vaccines contained either dead pathogens or live but attenuated pathogens. The latter are called live vaccines. For example, a live vaccine is a combined vaccine against mumps, measles and rubella. All other vaccines are ultimately dead vaccines. They can include a complete but inactivated pathogen, a part of it (e.g. spike protein) or a schematic of part of the pathogen such as mRNA and vector vaccines.

The term “inactivated vaccine” is very imprecise today. Today it is mainly used for whole virus vaccines, as is VLA2001. In an interview with Stern magazine, Valneva boss Thomas Lingelbach recommended talking about inactivated vaccines containing whole viruses instead of dead vaccines.

Valneva compared with other vaccines

Following positive results in the first two phases of the human clinical trial, Valneva began a Phase 3 trial in April 2021 with approximately 4,000 subjects 18 years of age and older. They received either the Valneva vaccine or the Astrazeneca vaccine twice over four weeks. Another two weeks later, the concentration of neutralizing antibodies in the blood was measured. According to Valneva, their own vaccine triggered a stronger antibody response than the Astrazeneca vaccine. Injection site reactions as well as fever, rash and swollen lymph nodes were common after vaccination. According to the manufacturer, there were no disturbing side effects. According to Valneva data, the third dose of the vaccine should significantly increase immunity.

However, when comparing the performance of seven different vaccines as a booster dose, Valneva was less effective than other vaccines. The results of the British study were published in the Lancet in early December 2021.

The Valneva vaccine should also work against the omicron variant, the company announced in mid-January. The laboratory study showed that the serum antibodies formed after three doses neutralized the omicron variant. All serum samples tested would show neutralizing antibodies against the original virus and the delta variant and at least 87 percent also against the omicron variant.

Application

Valnevy works in the same way as many other vaccines that have been used for a long time. The novelty, however, is the addition of DNA, which enhances the effect. The vaccine was able to demonstrate its effectiveness in several studies. There were no unusual reactions to vaccination or side effects. However, it cannot be ruled out that very rare side effects will only be detected after conditional approval. They only become visible after significantly more people have received the vaccine than in the studies.

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