New COVID-19 Vaccine Candidate Protects Against Coronavirus and Yellow Fever

Virologists from the Rega Institute of the KU Leuven (Belgium) have developed a vaccine candidate against Covid-19 that is based on the yellow fever vaccine and is therefore also effective against yellow fever. Results published today in nature show that the vaccine protects hamsters from infection with the SARS-CoV-2 Coronavirus after a single dose. The vaccine is also effective in monkeys. The team is currently preparing for clinical trials.

In order to develop their vaccine with the provisional name RegaVax, the team led by Professor Johan Neyts and Kai Dallmeier added the genetic code of the SARS-CoV-2 spikes to the genetic code of the yellow fever vaccine. The researchers tested the vaccine on healthy hamsters and monkeys. Another group of animals received a placebo.

The researchers first vaccinated the hamsters and then dripped the virus into their noses. Ten days after a single vaccine dose, most hamsters were protected against the virus. All hamsters were protected three weeks after vaccination. “You haven’t developed any lung infections either. In contrast, the lungs of the hamsters in the control groups showed clear signs of infection and disease, ”explains Neyts.

Virologist at the KU Leuven Rega Institute in Belgium. Photo credit: Layla Aerts for KU Leuven

The team also tested the vaccine in monkeys. “We observed neutralizing antibodies in some monkeys as early as seven days after vaccination. After fourteen days, high titers of neutralizing antibodies were measured in all animals. It’s very quick. In addition, the virus had completely or almost completely disappeared from their throats in the vaccinated animals. ”

Long lasting immunity

“Our vaccine is the only vaccine currently in development against Covid-19 that also protects against yellow fever,” explains Professor Neyts. The Rega team previously used the yellow fever vaccine as the basis for vaccine candidates against Zika, Ebola and rabies. “The effectiveness and safety of the yellow fever vaccine, which has been used for 80 years, is well known. More than 500 million people have already received this vaccine. One dose provides quick protection against yellow fever, which in almost all cases lasts for life. ”

“A vaccine against Covid-19 and yellow fever could make an important contribution to the WHO campaign to eradicate yellow fever by 2026,” continued Neyts. “Especially now that we know there are mosquito species in Asia that can transmit the yellow fever virus.”

A lab technician holds frozen virus samples at the KU Leuven Rega Institute. Photo credit: Layla Aerts for KU Leuven

RegaVax works after one dose, unlike many front runners in today’s race who require repeated vaccination after a month. “This has important logistical implications, especially for countries with a less advanced medical system,” explains Professor Neyts. “In addition, we expect the vaccine to offer permanent immunity to Covid-19. It could therefore be an ideal candidate for booster vaccination if immunity declines in people who have received a first generation vaccine. ”

Finally, the vaccine can be stored at 2-8 ° C, while some vaccines require a cold chain with temperatures as low as -70 ° C. This is already a challenge in the western world, but it may be nearly impossible to vaccinate large populations in remote tropical and sub-tropical regions, ”explains Neyts.

“A low-cost, single-dose vaccine that quickly protects against infection, can be stored and transported at refrigerator temperature and, like the yellow fever vaccine on which it is based, can lead to permanent immunity, provides an important and important effect of much-needed diversification of Covid -19 vaccine landscape, ”concludes Neyts.

His team is now preparing for clinical trials over the next year and has teamed up with a specialized and accredited company that will manufacture the vaccine candidate for human testing.

New technic

RegaVax is a vector vaccine: it uses the genetic code of the yellow fever vaccine virus as the carrier (or vector) for the genetic code of the coronavirus spikes. “When working with a related virus like Zika virus, parts of the genetic code of the yellow fever vaccine virus are exchanged for a similar part of the code of the target virus. Using this strategy, the team recently developed a Zika vaccine candidate. However, because SARS-CoV-2 is not related to yellow fever, a new technology had to be developed to insert a completely independent genetic sequence into the backbone of the yellow fever vaccine. This concerns an important innovation in the vaccine field. ”

Virus inhibitors

“Mind you: vaccines are not a solution for people who are already sick. It is for this reason that we are also developing a cure to help Covid-19 patients, ”concludes Neyts. “We recently published a report on the protective effects of the Japanese flu drug favipiravir on hamsters. We have identified some other existing drugs, or combinations thereof, that will inhibit the virus. We will now first examine its effect on infected hamsters. At the same time, we want to develop new and powerful virus inhibitors against SARS-CoV-2. For this purpose, we have already tested more than 1.6 million molecules in our fully automated laboratory for high biological safety. We’re looking for a needle in a haystack. ”

Reference: Lorena Sanchez-Felipe, Thomas Vercruysse, Sapna Sharma, Ji Ma, Viktor Lemmens, Dominique Van Looveren, Mahadesh Prasad Arkalagud Javarappa and Robbert Boudewijns: “Single-dose attenuated SARF-CoV-2 vaccine candidate with YF17D vector” Devlies, Laurens Liesenborghs, Suzanne JF Kaptein, Carolien De Keyzer, Lindsey Bervoets, Sarah Debaveye, Madina Rasulova, Laura Seldeslachts, Li-Hsin Li, Sander Jansen, Michael Bright Yakass, Babs E. Verstrepen, Kinga P. Böszörményi Gwendoline Kiemenyi-Kayere , Nikki van Driel, Osbourne Quaye, Xin Zhang, Sebastiaan ter Horst, Niraj Mishra, Ward Deboutte, Jelle Matthijnssens, Lotte Coelmont, Corinne Vandermeulen, Elisabeth Heylen, Valentijn Vergote, Dominique Schols, Zhongde Wang, Willy Bogers Thijs Kuiken, Ernst Verschoor, Christopher Cawthorne, Koen Van Laere, Ghislain Opdenakker, Greetje Vande Velde, Birgit Weynand, Dirk E. Teuwen, Patrick Matthys, Johan Neyts, Hendrik Jan Thibaut and Kai Dallmeier, December 1, 2020, nature.
DOI: 10.1038 / s41586-020-3035-9