Latest news in vaccine technologies

An interview with Professor Seppo Ylä-Herttuala from the A. I. Virtanen Institute for Molecular Sciences at the University of Eastern Finland.

Entirely novel vaccines, developed at record speed, have been employed to mitigate the coronavirus pandemic. The technology these vaccines are based on has however been investigated for over 20 years, and it has been successfully used in several patient studies in e.g. oncology.

Despite the fast development schedule of the coronavirus vaccines, the development process contains all the phases a normal schedule contains. No phase has been left out, and the safety of the vaccines has not been compromised. The first, preclinical part of the vaccine studies takes place in a laboratory. It is followed by the clinical part, where the vaccine is tested in the human body. The clinical part is divided into four phases, the fourth of which is carried out after the marketing authorization has been granted. Clinical vaccine development is very carefully controlled and follows strict ethical regulations.

The vaccines produced by the new techniques do not contain the virus or its particles. They contain the genetic code of the virus, which is recognized by the immune system cells of the body. This causes the production of antibodies against the pathogen.

“The adenovirus vaccines developed against the coronavirus are among the latest vaccine technologies,” says Professor Seppo Ylä-Herttuala from the A. I. Virtanen Institute for Molecular Sciences at the University of Eastern Finland.

“In addition to these, vaccines based on virus-like particles (VLP) have been manufactured for some time now. A good example of VLP vaccines is the papillomavirus vaccine developed at the Tampere University Vaccine Research Center.”

New kinds of vaccines are being developed against viruses with one or more spike proteins on their surfaces. The coronavirus has only one such protein.

RNA vaccines and adenovirus vaccines train the body to defend itself against the coronavirus

RNA stands for ribonucleic acid. An RNA vaccine does not contain virus but messenger RNA (mRNA), which in turn contains the recipe for the coronavirus spike protein. In other words, the mRNA instructs the muscle cells of the injection site to produce the spike protein. The body’s immune system recognises that the protein does not belong there and begins building an immune response by making antibodies. This way the body learns how to protect against future coronavirus infections.

The adenovirus vaccines do not contain a coronavirus either. Instead they contain a gene copied from the virus, which enables the body’s own muscle cells to produce the spike protein of the coronavirus. In the adenovirus vaccine this gene has been integrated into the genome of the viral vector. The adenovirus acts as a harmless carrier, which delivers the production instructions of the spike protein encoded in the gene, but will not replicate in the human body. When the muscle cell begins to produce the spike protein, the body recognizes the protein as foreign and begins to produce the antibody to the protein, which protects from the coronavirus infection.

Vaccination with a nasal spray

“Administering a vaccine through the nose is a natural delivery method when the virus is also transmitted through the airways. Nasal spray vaccines are currently being used against influenza,” Ylä-Herttuala says.

A pioneer in genetic medicine, Ylä-Herttuala is one of the founders of Rokote Laboratories, a Finnish company developing a nasal spray vaccine against the coronavirus. The vaccine is based on the adenovirus vector technology, and the company is currently seeking extra funding for clinical trials.

“No needles or injections are needed in the administration of a nasal spray vaccine. It protects the mucous membranes in the lungs and the nose more effectively than an intramuscular vaccine, and it can also prevent transmission of the virus. Like other adenovirus vaccines, our nasal spray can be stored in a fridge for a couple of weeks and requires no deep-freezing, which makes distribution and administration easy.”

Fast manufacturing with few adverse effects

“The main benefit of the new vaccine technologies is the high speed at which the vaccine can be manufactured. Whereas the manufacture of conventional vaccines is a lengthy, multiphase process, RNA and adenovirus vaccines are made in bioreactors,” says Ylä-Herttuala.

What about the adverse effects of the new vaccines? According to Ylä-Herttuala, the blood clot risk caused by the AstraZeneca vaccine has been exaggerated by media. For comparison, the risk of blood clots caused by contraception pills is about 400 times higher.

“That said, the new vaccines have only been in use for a short period of time. Any long-term side effects will gradually be discovered when we have more data.”

Suitability

“Clinical trials published so far have shown that both RNA and adenovirus vaccines are safe and effective on teenagers and adults. All age groups have reacted well and there is no upper age limit.”

RNA and adenovirus vaccines are not recommended for immunocompromised patients, such as those with severe cancer or recent organ transplantations. There is also the risk of a normal allergic reaction or anaphylaxis.

“Investigations are still ongoing into the cause of the extremely low risk of a blood clot, mostly occurring in women under 50 after the AstraZeneca vaccine. No certain evidence has so far been found.”

New vaccines will not replace the current ones

“New vaccines will not replace the current MMR vaccine against measles, mumps and rubella,” Ylä-Herttuala says.

But as regards viruses with few main proteins, the breakthrough of new vaccine technologies has already been made. However, it has so far not been possible to develop a vaccine against rapidly mutating viruses such as HIV.

Text by: Leena Koskenlaakso