Less than a decade ago, the United States had some 20 million doses A new smallpox vaccine — also effective against monkeypox — sat in the freezer at a national stockpile.
Such a large amount of the vaccine, known today as Genios, could have slowed the spread of monkeypox after it first emerged in the United States more than two months ago. Instead, the supply, known as the Strategic National Stockpile, had only 2,400 usable doses left in mid-May, enough to completely vaccinate only 1,200 people.
The rest of the dose had expired.
Now, about 10 weeks into the outbreak, high-risk people who want to get vaccinated have been unable to find a dose, and may not get one for months.
The chain of events that led the stockpile of the now-critical vaccine to almost nothing in the United States is only now emerging.
At several points federal officials opted not to refill quickly when doses had expired, instead investing money in developing a freeze-dried version of the vaccine, which would have significantly increased its three-year shelf life. .
As the wait for a freeze-dried vaccine approved by the Food and Drug Administration dragged on over the past decade, the United States purchased large quantities of raw vaccine products that have not yet been filled into vials.
Incomplete vaccines are stored in large plastic bags outside Copenhagen, which is the headquarters of the small Danish biotech company Bavarian Nordic, which developed Jynneos and remains its sole manufacturer.
For nearly 20 years, the United States government has helped fund the company’s vaccine development, clinical trials, and manufacturing process. crossed the $1 billion mark by 2014 And moving towards $2 billion. Despite this, the United States now finds itself unable to obtain enough doses to launch a widespread vaccination campaign for those at highest risk: men who have sex with men, and in particular, those who have multiple partners. Huh.
One reason Jynneos missed the US stockpile is that federal officials overseeing it did not see monkeypox, which has a relatively low mortality rate, as a problem, or at least their problem. They focused on the most dangerous and deadly scenarios, such as bioterror attacks involving smallpox or anthrax.
“We have to prepare against many threats with a limited budget,” said Dr. Gary Disbrow, director of the Biomedical Advanced Research and Development Authority. barda, the federal agency that supported the development of Jynneos and other drugs and vaccines to protect against pandemics, bioterrorism and other threats. “Our plan was for smallpox.”
What’s to know about the monkeypox virus?
What is monkeypox? Monkeypox is a virus similar to smallpox, but the symptoms are less severe. It was discovered in 1958 after an outbreak in monkeys kept for research. The virus was found mainly in parts of Central and West Africa, but in recent weeks it has spread to dozens of countries and infected thousands of people, including more men who have sex with men. Is. On 23 July the World Health Organization declared monkeypox a global health emergency.
A former federal official, Dr. Ali S. The limited supply of Genios currently available is evidence that a new approach is needed for biological hazards and pandemic preparedness, said Khan, who was running the Office of Disease Control and Prevention until 2014. inventory. “I want people to know how bad it was given the money and resources put into it,” he said.
Fears of 9/11 and Bioterrorism Attacks
After the September 11, 2001, terrorist attacks and the subsequent anthrax letter attacks, the United States government doubled its efforts to prepare against future threats. A clear threat was smallpox, which had a 30 percent mortality rate. Although the virus was declared extinct in 1980, laboratory samples of it exist, and there has been a long-standing concern that a foreign country or terrorist group might weaponise it.
In the years following September 11, the United States stockpiled more than 100 million doses of the smallpox vaccine—the version of the vaccine that wiped out the virus. With names like Dryvax and ACAM2000, they use live vaccinia virus that replicates and can have dangerous side effects, including heart inflammation in about six out of 1,000 recipients. One or two people are expected to die per lakh vaccinations.
After 2001, the United States sought an effective smallpox vaccine with fewer side effects. In 2003 it began pumping millions of dollars into Bavarian Nordic, a small company with a promising new smallpox vaccine.
The vaccine came in vials in liquid-frozen form, with a shelf life of three years at temperatures the US government stored them at: -20 °C, slightly cooler than a kitchen freezer.
The new vaccine, then known as Imvamune, not Genios, was never intended to replace the large stockpile of older generations of smallpox vaccines, but rather to be introduced. high risk people According to complications from older vaccines and their family members, for the 2014 report by the US Department of Health and Human Services. This included people with conditions ranging from eczema to HIV and pregnant women and infants.
Some CDC officials recall being skeptical. Jynneos required two shots—not ideal in the event of a bioterror attack—instead of one. And although traditional smallpox vaccines can cause serious complications, complications will be less of a concern than smallpox mortality.
But Bavarian Nordic officials told shareholders the long-term US plan was to stock enough to vaccinate all 66 million eligible people in high-risk households.
In 2009, the company received a $95 million contract from the United States to develop freeze-dried formulations with a shelf life of five to 10 years.
As the 20 million Genio doses began to run out, the United States ordered another eight million, which were shipped to the nation’s stockpile in 2015, according to Bavarian Nordic and U.S. Health and Human Services personnel. that order was to be “a bridge” Primarily until the emergence of the freeze-dried version, according to a federal planning body of health and human services personnel.
A former federal official, Dr. Ali S. Khan, who until 2014 ran the CDC office managing the stockpile, recalled being “frustrated at why it was taking so long to achieve freeze-dried preparations that could have been held for longer. “
But eight million doses were the last substantial shipment for years. Since 2015, the United States has instead placed orders for a bulk vaccine product worth hundreds of millions of dollars – basically raw vaccines stored in large bags, which are converted into freeze-dried doses after the company completes the process. and required FDA approval.
As of 2017, the national Jynneos stockpile had exhausted all 27,993,370 doses, although it still had a large stockpile of other smallpox vaccines in the United States.
“In fairness, I’m not sure anyone in their right mind would have thought we needed more smallpox vaccines,” said Dr Nicole Lurie, who served as her assistant secretary for preparedness and response within Health. During the tenure of eight years, the stock was inspected. Human Services under President Barack Obama.
Jynneos and older stored smallpox vaccines, such as ACAM2000, are both good choices as smallpox vaccines, but not to the same degree as in the case of monkeypox. Although federal officials expect the ACAM2000 to protect against monkeypox and have shipped doses to local health authorities for useIts harsh side effects make many doctors uncomfortable using it for the massive monkeypox vaccination campaign.
one delay after another
The freeze-dry vaccine production target has taken longer than expected, partly because of the slow FDA review process. In recent years the Bavarian Nordic also underwent an expansion that would eventually delay the delivery of vaccine doses.
The Bavarian Nordic had long relied on outside companies for the final stages of the production process, such as filling the actual vials. It is normal, that HHS has invested In “fill and finish” companies to reduce the risk of them emerging as a bottleneck during a pandemic.
By 2017, it had plans to build its own “fill-finish” facility, which would make its vaccine production “more profitable than what we’ve seen in the past,” according to Bavarian Nordic chief executive Paul Chaplin. The government is funding a portion of this expansion.
In early 2020, the United States placed an order for 1.4 million liquid-frozen doses from Bavarian Nordic, its first significant order for a ready-to-use product in years. Some of those doses – about 372,000 – were filled by a third-party contractor, and have until now been the main source of doses for the country’s monkeypox vaccination program.
The rest of the Bavarians were filled at Nordic’s new fill-finish facility, which got underway in 2021.
But the FDA did not inspect the facility until the monkeypox outbreak began, and considered those doses unusable until the inspection took place. As a result, the bulk of the 1.4 million-dose order sat in Denmark until last month, when FDA inspectors arrived.
Now, the US government has told Bavarian Nordic to start sending doses as soon as possible, setting aside its goal of a freeze-dried formulation for now.
but it could be months ago US officials say the company is able to deliver millions more doses than the supply that the United States has been paying Bavarian Nordic for years.
With little genos to prevent an outbreak of monkeypox, federal officials are taking a fresh look at the finished dosage, which is still on hand. Health and Human Services officials have sent the samples back to the Bavarian Nordic for testing.
Officials say it is “very unlikely” that they are still viable. But if they are, the Administration for Strategic Response and Preparedness, a division within HHS, said it would make them “available for response.”
Sheryl Gay Stolberg Contributed reporting.