Closing treatment gaps in yellow fever: are germ-free egg-based vaccines the answer? 

Once thought to be under control, yellow fever is making an alarming comeback, and the numbers are climbing. With treatment gaps that prevent yellow fever from being eradicated, new approaches are being sought after to curb infection rates, a major one being germ-free egg-based vaccines.  

Yellow fever cases on the rise: how can vaccines control spread? 

Around 212 cases of yellow fever, including 85 deaths, were reported in the six months to April 2025, according to the World Health Organization (WHO). These cases were reported in Bolivia, Brazil, Colombia, Ecuador, and Peru. Yellow fever cases are endemic in the tropical regions of Central and South America and Africa. In fact, in Columbia, a nationwide emergency was declared when at least 34 people died of yellow fever in April. 

The WHO blames increased sylvatic transmission cycles for the recent spike in cases. A sylvatic transmission cycle refers to the natural process of a pathogen in which it spreads in animals, even via carrier animals, like mosquitoes in the case of yellow fever. So, the higher the number of these cycles where yellow fever-causing viruses called flaviviruses circulate, the higher the rate of infections in humans when they are bitten by mosquitoes carrying the virus. 

Catherine Caulfield, chief executive officer (CEO) and co-founder of Irish vaccine maker Ovagen, explained that yellow fever is an acute viral hemorrhagic disease, meaning that infection is accompanied by intense bleeding, which can be fatal. Some patients experience high fever, and organs like the liver and kidneys are affected in the more toxic phase, even after patients have recovered from the initial symptoms. Many of these people are also likely to develop jaundice – caused by the excess of a pigment called bilirubin in the blood – resulting in the yellowing of the skin and eyes, hence the name yellow fever. 

Sanofi’s YF-VAX vaccine is probably the best-known yellow fever vaccine in the market at present. It has been prepared by culturing a specific strain of the yellow fever virus that is found in chicken embryos. When the weakened strain is injected through the skin, it elicits an immune response, and antibodies against yellow fever prevent infection. A single dose of the yellow fever vaccine provides long-lasting protection; however, it is an expensive vaccine, priced between $220 and $250 for people traveling to or living in endemic areas, according to a report by Better Care. 

As cases escalate, there is a need for cheaper alternatives. Caulfield’s company Ovagen wants to “transform vaccine production” by implementing germ-free technology in yellow fever vaccine development. 

“The technology offers immediate scalability and significant margins for manufacturers, all while reducing waste and environmental impact. For public health systems and vaccine developers alike, it enables faster response times, lower costs, and substantially increased yellow fever viral yield per egg, which means increased vaccine doses per egg, therefore improving access for poorer nations and increased resilience in the face of a public health crisis,” Caulfield told Labiotech. 

Yellow fever vaccines: how can germ-free eggs bring costs down? 

A germ-free egg is completely free of bacteria. Germ-free chickens breed naturally, and scientists make sure that they are kept in conditions that don’t have bacteria and other pathogens lurking around. Some of these measures include filtering the air where the chickens live, sterilizing bedding, food, and water, employing an automated system for egg collection and packing, routine monitoring, and maintaining maximum biosecurity. 

There are several merits to eliminating bacterial contamination. As antibiotics are typically required in traditional egg-based manufacturing, this can lead to antimicrobial resistance, which occurs when parasites change over time and no longer respond to medicines. Antimicrobial resistance is no longer a worry with germ-free eggs as the use of antibiotics dwindles. Caulfield believes this is a “holy grail for vaccine manufacture.”  

This also substantially increases vaccine yield per egg, and improves quality, security, and sustainability, according to Caulfield. 

Moreover, this process cuts the carbon footprint as fewer eggs are required to produce the same number of vaccines, and there is a drop in waste and costs that are linked to contaminated batches being thrown out. This in turn allows for more efficient and cost-effective production of vaccines, therefore improving access for poorer nations, Caulfield pointed out. 

“This yield advantage significantly lowers the cost per dose and drastically improves production efficiency, with major cost-saving implications, combining scalability with the elimination of the use of antibiotics in vaccine manufacture,” said Caulfield. 

The platform, which is ready for the market now, has been validated with a viral yield study proved the technology’s benefit. Ovagen’s germ-free eggs produced up to 1,350 times more yellow fever virus strain 17D – the same strain in YF-VAX – compared to the conventional specific pathogen free (SPF) eggs. The latter has been regarded as the industry’s current gold standard for a long time. This study was conducted independently by the Pirbright Institute, a research center in the U.K. 

While each SPF egg can generate 300 to 400 vaccine doses, a germ-free egg could create up to 7,600 doses of vaccine. Simply put, germ-free eggs are far more cost-effective than traditional manufacturing techniques. 

“That is the kind of game-changing innovation and disruption that changes the economics of global vaccine production,” said Caulfield.  

New research related to yellow fever vaccines

• Immunogens and Vaccine Compositions against Flavivirus – Henry Jackson Foundation 
• Recombinant Flavivirus (including Dengue and Zika) Quaternary Epitopes for Vaccines and Diagnostics – The University of North Carolina at Chapel Hill 
• Vaccine Stabilizing Silica-Coating Technology – Portland State University   

The germ-free egg platform could greatly cut the reliance on SPF eggs to meet manufacturing needs. Currently, there is a global shortfall of 60 million doses, and to hit the mark, traditional approaches would require more than 140,000 eggs. Ovagen’s germ-free method would take less than 8,000 eggs to get there, greatly reducing costs, time, eggs, and antibiotics. 

“What we have developed isn’t incremental; it’s a complete rethink of the vaccine manufacturing process. Our germ-free egg platform eliminates bacterial contamination and reduces the need for antibiotics in vaccine production while delivering significantly higher viral yield. This is high-impact science with high-value commercial outcomes,” she said. 

Island Pharmaceuticals’ Galidesivir targets viruses 

Meanwhile, Australian company Island Pharmaceuticals is moving fast with its antiviral drug called Galidesivir to address viral infections, including yellow fever. Galidesivir is an analogue – a substance that has a similar structure to another – of the compound adenosine, a building block of genetic material like RNA. The antiviral works by binding to the region in the virus’ RNA where adenosine would typically bind, causing a structural change to the virus. This disrupts enzyme activity in the virus, thereby blocking its pathogenic effects. 

The antiviral, which was bought from American pharmaceutical BioCryst Pharmaceuticals in July, is in the running for approval to treat Marburg virus, another hemorrhagic fever virus. Island will soon be in talks with the FDA to get the green light. This could pave the way for approval in yellow fever, despite BioCryst’s pause on clinical trials for Galidesivir in 2021. 

Yellow fever outbreaks amid budget cuts: time for efficient strategies 

As infectious disease and vaccine research have faced setbacks in the U.S. owing to recent budget cuts, pandemic preparedness has taken a hit. Yellow fever deaths declined in the 2000s, and other infectious diseases like the deadly meningitis A were wiped out thanks to vaccines and emergency stockpiles. Indeed, yellow fever saw the biggest gains in routine vaccine programs, as they slashed death rates by 99 per cent, according to a 2025 United Nations report. 

But this progress is now at risk, warned the United Nations. 

“Funding cuts to global health have put these hard-won gains in jeopardy,” said Tedros Adhanom Ghebreyesus, director-general of the World Health Organization, in a report. 

With yellow fever making a comeback as outbreaks plague regions in South America and Africa in 2025, there is a demand for efficient ways to halt the spread. And Ovagen’s germ-free vaccines might just be the solution we have been looking for.