The ZIKA virus - transmitted primarily by mosquitoes - usually causes mild symptoms or is asymptomatic, but it can also cause serious birth defects in infants born to women infected during pregnancy.

In 2015, a sharp increase in the number of ZIKA virus infections began to be observed around the world, especially in Central and South America. It was then that scientists from Gdańsk came up with the idea of preparing a vaccine against this virus. 'The work lasted from 2016 to 2022, and began during the Zika virus epidemic in South America,’ says Dr. Ewelina Król, dean of the Intercollegiate Faculty of Biotechnology of the University of Gdańsk and the Medical University of Gdańsk, the project leader.

She adds that at that time 'many studies were being conducted in various scientific centres and biotechnology and pharmaceutical companies. Every now and then, there were new reports about new types of vaccines being tested - or ones with better effectiveness. It was necessary to conduct research at a rapid pace and study many different factors affecting the effectiveness of the preparation, which took a lot of time. Ultimately, despite many clinical trials, so far no vaccine against ZIKA has been introduced onto the market.'

Work by Gdańsk scientists from the Intercollegiate Faculty of Biotechnology of the University of Gdańsk and the Medical University of Gdańsk, including Dr. Gabriela Brzuska, Dr. Anna Czarnota and Professor Bogusław Szewczyk, led to the creation of a prototype of a vaccine against the Zika virus.

Team leader Dr. Król explains that the subject of the invention are amino acid sequences of modified, recombinant Zika virus proteins (ZIKV) or recombinant virus-like particles (VLPs) containing at least two Zika virus proteins. 

She told PAP - Science in Poland: ’Under natural conditions, two ZIKV envelope proteins (prM and E) create virus-like particles, i.e. highly organized structures resembling the virus, but without genetic material. VLPs can be produced in various types of eukaryotic cells (mammalian, insect, protozoan cells), but this production is usually inefficient.

'Our invention involved introducing certain modifications to the amino acid sequences of the structural proteins of the Zika virus (E and/or prM) in order to increase the production of VLPs in eukaryotic cells. The modifications we introduced were also aimed at increasing the immunogenic potential of VLPs, i.e. the ability to induce immune response after administration as a vaccine. Thanks to this, the body can protect itself more effectively against Zika virus infection.’

Until recently, there were two important directions in the approach to work on new vaccines for flaviviruses, the family of which includes the ZIKA virus. One of them was the creation of vaccines based on inactivated or attenuated viruses. Inactivated viruses are viruses that have been exposed to factors that kill them (e.g. temperature or chemicals). Attenuated viruses are selected strains of viruses - so weakened or so changed that they are unable to multiply in the body and pose no threat to human health. Attenuated viruses are used in vaccines against yellow fever or dengue, and inactivated ones - in vaccinations against tick-borne encephalitis or Japanese encephalitis. Currently, however, work is mainly focused on the development of recombinant vaccines.

Dr. Król says: 'The effectiveness of the prepared antigen has been tested in vivo (in a living organism - PAP), in a mouse animal model. We have demonstrated that the recombinant VLPs, which are the subject of the invention, can be a component of a vaccine that will induce an immune response in the body.’

In addition to the antigen, the vaccine most often contains additional ingredients, including an adjuvant, whose role is to strengthen the immune response. 'In our research, we tested the effectiveness of various adjuvants in combination with the antigen we had developed. Our preparation was tested on an animal model, but in order to become a vaccine, it still requires many preclinical and clinical human trials,’ says Dr. Król.

A patent for the invention (named 'Sequences of recombinant flaviviral virus-like particles and their medical application to prevent Zika virus infections') has been awarded by the Polish Patent Office. 'The application also covers the use of recombinant proteins or virus-like particles as an immunogenic element of a vaccine to prevent Zika virus infections and as a diagnostic antigen for detection of flavivirus infections, especially Zika virus, tick-borne encephalitis virus and dengue virus,’ says Dr. Król.

Despite the allocation of significant funds for the development of a vaccine immediately after the ZIKA virus outbreak in 2015, there are currently no approved preparations against the Zika virus on the market. Work on most products remains in the preclinical or early clinical phase. 'Currently, work on the development and introduction of a vaccine against the Zika virus has slowed down significantly, as the number of cases around the world has significantly decreased, and, consequently, the funding for research on this topic has also decreased,’ says Dr. Król.

She adds that the outbreak of the SARS-CoV-2 virus pandemic additionally caused pharmaceutical companies to change their research profile in order to develop a vaccine against COVID-19 as quickly as possible.

When asked what distinguishes the solution of Gdańsk scientists from those developed around the world, she says that her team introduced 'several modifications to the natural sequences of structural proteins of the Zika virus: modification of the signal sequence, modification of the sequence separating structural proteins and modification of the transmembrane domain of the main envelope protein of the Zika virus. So far, there have been no reports in the literature about such sequence changes. Natural sequences of ZIKA proteins are most often used in solutions,’ the scientist adds.

Continuing, she says: ‘All the introduced modifications were aimed at obtaining virus-like particles in a form as close as possible to the native viral particle, increasing the efficiency of their production in the expression system, as well as increasing their immunogenicity, i.e. the ability to stimulate the immune system to produce virus-neutralizing antibodies.’

The Zika virus is transmitted to humans primarily by Aedes mosquitoes, including the Egyptian mosquito and the tiger mosquito. However, infection can also occur during sexual intercourse, and the virus can also be transmitted from a pregnant woman to the foetus.

Most people infected with Zika have no or mild symptoms, such as fever, rash, joint and muscle pain, red eyes, and headache. The infection is usually not life-threatening and makes the person immune to further infections with this virus. However, in a pregnant woman an infection with the virus may result in a serious birth defect in the child, such as microcephaly and an underdeveloped brain.

The Zika virus belongs to the flavirus family, which also includes the following viruses: dengue, yellow fever, West Nile and tick-borne encephalitis.

Vaccination, which is intended to protect against viral infection, involves providing the body with a safe stimulus that forces the body to produce antibodies to fight the infection. The idea is that the body can learn to recognize and fight specific pathogens in safe conditions. Thanks to this, if one becomes infected in the future, the body has an 'arsenal' in the form of neutralizing antibodies ready to fight the pathogen.

PAP - Science in Poland, Anna Mikołajczyk-Kłębek

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