Classic tech meets new science: How a chicken egg could help end the pandemic

Updated March 29, 2022, to include link to peer-review journal article on interim results from the Phase 1 clinical study of the NDV-HXP-S vaccine candidate in Thailand.

During the 2009 influenza A/H1N1 pandemic, PATH began preparing for the next global outbreak. PATH partnered with vaccine manufacturers in low- and middle-income countries to increase egg-based flu vaccine production capacity.

The next “big one” turned out to be the coronavirus pandemic. Scientists have developed a handful of safe, effective vaccines against COVID-19 at unprecedented speeds, but demand is seriously outpacing supply—and distribution is far from equitable.

Many low- and middle-income economies continue to be last in line for doses. As of last month, high-income countries had purchased more than half of the COVID-19 vaccine supply, while low-income countries had purchased around 9 percent of available doses.

Reversing this trend is vital, and the preparations made for flu might play a key role in improving vaccine supply for COVID-19.

“COVID-19 showcases the critical importance of resilient immunization systems that can protect communities in a crisis and sustain coverage when the crisis is over,” says Dr. Vu Minh Huong, PATH Vietnam regional technical advisor. “We won’t be able to end the pandemic or control the virus’ spread without more vaccines that people can access over the long term, no matter their income level.”

That’s why PATH is working with manufacturers in Vietnam, Thailand, and Brazil, as well as renowned US researchers to advance the development of a new, affordable COVID-19 vaccine designed to increase access for more people.

Inspired by flu vaccines in longtime use, this one leverages the power of an old friend—the chicken egg.

Currently, manufacturing capacity for existing COVID-19 vaccines is limited for a variety of reasons, including intellectual property laws and other technological constraints posed by the vaccines’ formulas. Adding an egg-based COVID-19 vaccine to the arsenal could help close the access gap in several ways.

Affordability and deliverability. With relatively low production costs and stability at regular refrigerator temperatures (2°C to 8°C) for months, an egg-based vaccine could be a practical platform for reaching resource-limited communities.

Untapped production capacity. Many manufacturers already have the infrastructure to make egg-based vaccines, including in low- and middle-income parts of the world.

In fact, more than a billion safe and effective egg-based flu vaccine doses are made annually worldwide. These facilities lay idle half the year when not making seasonal flu vaccine—and could be converted to make large volumes of COVID-19 vaccine in the off-season (or more often if needed). Capacity in Vietnam, Thailand, and Brazil combined could yield hundreds of millions of doses per year.

“In short, more suppliers entering the market means more supply and more people vaccinated,” says Dr. Bruce Innis of PATH’s Center for Vaccine Innovation and Access. “This is why PATH is doing what we can to help advance this versatile technology.”

Greater supply control for countries. As an option that countries could produce themselves or export regionally, an egg-based COVID-19 vaccine could both address the pandemic and provide a reliable backbone for routine immunization.

And it would give more countries access without having to wait in line behind much wealthier nations—a problem that COVID-19 brought to light. Having homegrown vaccines would reduce dependency on expensive and scarce imported vaccines.

For decades, the most common influenza vaccines have been made by growing flu virus in chicken eggs and inactivating or weakening it so it can’t cause disease. This modified virus induces the body to recognize invading flu and build a protective immune response.

Now, clinical development is underway in Vietnam, Thailand (see Phase 1 interim results in eClinicalMedicine), and Brazil, to evaluate a new egg-based COVID-19 vaccine inspired by the flu experience. It’s based on a novel vaccine platform that brings together traditional egg-based technology with new, cutting-edge science—and uses another virus as a building block.

Scientists genetically modify a Newcastle disease virus (NDV)—usually used in its live form, in vaccines for poultry—so that its surface presents the SARS-CoV-2 stabilized spike protein (known as HexaPro). That key spike protein trains the immune system to recognize and fight COVID-19 infection. NDV is grown in eggs, purified, inactivated (or killed), and formulated into an injectable vaccine.

This one-of-a-kind vaccine design wouldn’t have been possible without international collaboration.

The Institute of Vaccines and Medical Biologicals (IVAC) in Vietnam, Government Pharmaceutical Organization (GPO) in Thailand, and Butantan Institute in Brazil—all established flu vaccine manufacturers—are driving the studies and overall development.

Drs. Peter Palese, Adolfo Garcia-Sastre, and Florian Krammer at the Icahn School of Medicine at Mount Sinai in New York developed the recombinant NDV technology. A team at the University of Texas at Austin (UT Austin) led by Drs. Jason McLellan, Ilya Finkelstein, and Jennifer Maynard developed the stabilized spike protein—an earlier version of which forms the basis of several other widely used COVID-19 vaccines.

As COVID-19 emerged, PATH and colleagues wondered what it would take to harness the power of egg-based vaccines. Could they help fill gaps left by the market-driven vaccine development that leaves billions of people behind? Was such a vaccine technically possible?

To answer these questions, we brought together the international consortium, with PATH playing a key role as connector, facilitator, and technical advisor. After conversations with Mount Sinai, UT Austin, and the manufacturers in Vietnam, Thailand, and Brazil, the answer appeared to be “yes.”

Leveraging our immunization expertise and networks, PATH linked the technologies and partners needed to develop the vaccine—alliances unlikely to come together otherwise. We have also been contributing our considerable clinical, regulatory, and quality standards expertise in an advisory role across the consortium, particularly in Vietnam where we have locally based expert staff.

Enabled by license agreements with Mount Sinai and UT Austin, PATH has been helping IVAC and GPO access the NDV and HexaPro technologies via affordable sub-licenses. This is done under terms conducive to ensuring access for low- and middle-income economies. Plans to secure sub-licenses for Butantan Institute are in the works.

Each institution involved is dedicated to cooperation, information sharing, and the public good—a spirit reflecting the unprecedented collaboration seen around the world in response to the COVID-19 crisis.

Other countries are already showing interest in the technology. Results from the first clinical study, which will be available in the next few months, will offer a clue as to how the vaccine performs in people. Those results will inform future development strategies.

If these egg-based vaccines work like experts expect they will, then more countries will be able to vaccinate more people, strengthening immunization systems to better control COVID-19 for the foreseeable future. Success may also offer additional insights into this platform’s potential to help improve vaccine equity for other diseases.

Learn more about PATH’s Center for Vaccine Innovation and Access and our COVID-19 vaccine work.

Additional resources:

• New York Times article, “Researchers Are Hatching a Low-Cost Coronavirus Vaccine”
• PATH responds to COVID-19 web page