The genetically altered yellow fever vaccine was highly effective in animals. If it passes clinical trials, the new vaccine would have some advantages over other SARS-CoV-2 vaccines.

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The research suggests that the newly developed vaccine would not only protect against COVID-19 but also against yellow fever.

In addition, it appears to provide protection after a single shot, whereas SARS-CoV-2 vaccines such as the one that Pfizer and BioNTech have developed require two doses 1 month apart.

“This has important logistical implications, in particular for countries with a less advanced medical system,” explains Prof. Johan Neyts, from the Rega Institute at KU Leuven in Belgium. Prof. Neyts is one of the virologists who led the research.

Prof. Neyts also believes that the vaccine may offer long lasting immunity against COVID-19.

“It could therefore be an ideal candidate for repeat vaccinations when immunity decreases in people who have received one of the first-generation vaccines,” he says.

The study, which appears in the journal Nature and as a preprint, suggests that a single shot of the vaccine protected hamsters against SARS-CoV-2, which is the virus that causes COVID-19. It also protected mice and monkeys.

The team is now preparing to conduct clinical trials of the new vaccine, which is provisionally called RegaVax, in 2021.

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The standard yellow fever vaccine, known as YF17D, has been in use for 80 years and has a good safety record. It delivers a live, “attenuated” (weakened) strain of the yellow fever virus.

The team at KU Leuven had previously used the same virus as the basis of candidate vaccines against the Zika, Ebola, and rabies viruses.

The scientists use the yellow fever virus as a “vector” to deliver fragments of genetic material from other viruses. The fragments provoke a targeted immune response and long-term immunity to future infections.

Vaccines that employ the yellow fever virus as a vector are already licensed for use against Japanese encephalitis and dengue viruses.

To create their SARS-CoV-2 vaccine, the virologists at KU Leuven inserted a genetic sequence from SARS-CoV-2 into the yellow fever virus.

The sequence is a blueprint for SARS-CoV-2 spike proteins, which give the virus its characteristic crown-like appearance. When host cells become infected with the weakened yellow fever virus, they make copies of the spike, which, in turn, provoke an immune response.

To test the vaccine, the researchers gave a single dose to hamsters, which are an established model of SARS-CoV-2 infection.

When they dripped a solution of SARS-CoV-2 into some of the animals’ noses 10 days later, most were immune to infection.

Around 3 weeks after vaccination, all the animals the researchers tested were immune.

None of the vaccinated hamsters developed any signs of lung infection, whereas hamsters that received the inactive control vaccine showed clear signs of lung disease.

The researchers also tested the vaccine in monkeys. They detected low blood levels of “neutralizing” antibodies, which disable the virus, 7 days after vaccination. After 14 days, however, there were high concentrations in the animals’ blood.

“This is very fast,” says Prof. Neyts. “Moreover, in the vaccinated animals, the virus was completely or nearly completely gone from their throats.”

More than 500 million people worldwide have received the original yellow fever vaccine, which usually provides lifelong protection.

“A vaccine that works against COVID-19 and yellow fever could offer an important contribution to the WHO’s campaign to eradicate yellow fever by 2026,” says Prof. Neyts. “Especially now that we know there are mosquito species present in Asia that can transmit the yellow fever virus.”

Another important advantage of the newly developed vaccine is that it can be stored at 36–46°F (2–8°C). By contrast, Pfizer and BioNTech’s SARS-CoV-2 vaccine must be stored at -94°F (-70°C).

“That’s already challenging in the Western world, but it may be nearly impossible to vaccinate large populations in remote tropical and subtropical regions,” says Prof. Neyts.

Only clinical trials can reveal whether or not the vaccine is safe and effective in humans. However, the researchers are optimistic that it will provide rapid, strong immunity after a single dose.

In the preprint of their paper, they conclude:

“In light of the threat [that] SARS-CoV-2 will remain endemic with spikes of reinfection, as a recurring plague, vaccines with this profile may be ideally suited for population-wide immunization programs.”

They note that a limitation of the original yellow fever vaccine is its unsuitability for people over 60 years of age and anyone with reduced immunity. These two groups are particularly vulnerable to COVID-19.

However, the study authors report that their new candidate vaccine appeared to be safer, at least in mice, than the older vaccine on which they based it.

“These preliminary, though encouraging, data suggest that [the new vaccine] might also be safe in those persons most vulnerable to COVID-19,” they write.

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