Less than a decade ago, the United States about 20 million doses A new smallpox vaccine – which is also effective against monkeypox – is placed in a freezer in the national stockpile.
Such large quantities of the vaccine, known today as Jynneos, may have slowed the spread of monkeypox after it first appeared in the United States in mid-May. Instead, the supply, known as the Strategic National Reserve, had only about 2,400 usable doses left at the time, enough to fully immunize 1,200 people.
The remainder of the dose has expired.
Now, about 10 weeks after the outbreak, many high-risk people who want the vaccine have been unable to find a dose and may not be able to find it for months.
The chain of events that caused the now vital vaccine stockpile to be depleted to almost nothing in the United States has just emerged.
At some point, federal officials chose not to quickly replenish doses as they expired, instead pouring money into developing a freeze-dried version of the vaccine that could dramatically increase its shelf life. its three years of use.
As the wait for a freeze-dried vaccine to be approved by the Food and Drug Administration drags on over the past decade, the United States has purchased large quantities of raw, unfilled vaccine product.
The raw, unfinished vaccine is still stored in large plastic bags outside Copenhagen, at the headquarters of the small Danish biotech company Bavarian Nordic, which developed Jynneos and remains the sole manufacturer. its.
For nearly 20 years, the US government has helped fund the company’s vaccine development, clinical trials, and manufacturing processes, at a cost crossed the $1 billion mark in 2014 and is down to 2 billion dollars. Even so, the United States cannot currently procure enough doses to rapidly launch a widespread vaccination campaign for those most at risk: men who have sex with men, and especially those with multiple sexual partners. .
One reason for the reduction in the US stock of Jynneos is that the federal officials overseeing it did not see smallpox in monkeys as a problem, or at least their problem. They focus on the most dangerous and deadly situations, such as a bioterrorism attack involving smallpox or anthrax.
Dr Gary Disbrow, Director of the Biomedical Advanced Research and Development Authority, said: “We have to prepare against many threats with limited budgets. BARDA, the federal agency that has supported the development of Jynneos and other drugs and vaccines to protect against pandemics, bioterrorism, and other hazards. “Our plan is for smallpox.”
Things to know about 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 of disease in monkeys kept for research. The virus is mainly found in parts of Central and West Africa, but in recent weeks it has spread to dozens of countries and infected tens of thousands of people, overwhelmingly men. same-sex sex. On July 23, World Health Organization declares monkeypox a global health emergency.
Currently, monkeypox has emerged as a serious public health threat. As of the end of July, more than 5,000 cases have been reported in the United States, and there are nearly 1,300 in New York City.
A spokesperson for the Department of Health and Human Services said: “We are required to have a vaccine for smallpox, based on the identification of a physical threat that simply does not exist to the disease. Smallpox in monkeys”. “Today, as we are in public health threat response mode, we are working rapidly around the clock to accelerate the number of doses available.”
The limited supply of Jynneos available suggests a new approach is needed to prepare for biological and pandemic threats, a former federal official, Dr. Ali S. Khan, said so far. In 2014, the office of the Centers for Disease Control and Prevention managed the stockpile of . “I want people to know how badly this has gone with the money and resources invested in it,” he said.
9/11 and the fear of a bioterrorism attack
After September 11, 2001, terrorist attacks and subsequent attacks in anthrax chữ, the US government has redoubled its efforts to prepare against future threats. One obvious danger is smallpox, with a mortality rate of 30%. Although the virus was declared eradicated in 1980, laboratory samples of it persist and there has long been concern that a foreign country or a terrorist group could weaponize it.
In the years since September 11, the United States has stockpiled more than 100 million doses of the smallpox vaccine — the version of the vaccine that has eradicated the virus. With names like Dryvax and ACAM2000, they use a live virus that can replicate and can cause dangerous side effects, including heart inflammation in about six out of every 1,000 people. One or two out of millions of vaccinated people are expected to die.
After 2001, the United States searched for an effective smallpox vaccine with fewer side effects. In 2003, they began pumping millions of dollars into Bavarian Nordic, a small company with a promising new smallpox vaccine.
By 2013, Bavarian Nordic distributed 20 million doses its new smallpox vaccine for Strategic National Reserveaccording to the company’s annual report as well as US documents.
The vaccine is packaged in a vial in a liquid frozen form with a shelf life of three years.
The new vaccine, formerly called Imvamune, not Jynneos, was never intended to replace the much larger stockpile of older generations of smallpox vaccines, but was provided for people at higher risk complications from older vaccines and their family members, according to to a 2014 report by the United States Department of Health and Human Services. That includes people with conditions ranging from eczema to HIV, pregnant women, and babies.
Some federal health officials are skeptical. Jynneos requires two shots – not ideal in the event of a bioterrorism attack – and not one.
But Bavarian Nordic executives told shareholders that the long-term US plan is to stockpile enough Jynneos vaccine to immunize all 66 million eligible people in high-risk households.
In 2009, the company received a $95 million contract from the United States to begin development of a freeze-dried formulation with a shelf life of 5 to 10 years.
As 20 million doses of Jynneos began to expire, and with a free-dried version still in development, the United States ordered another 8 million doses, which were shipped to the nation’s stockpile in 2015, according to reports. Bavarian Nordic and the United States Department of Health and Human Services.
Dr. Kahn, a former federal official, recalls “disappointment as to why it took so long to get a freeze-dried preparation that could keep for longer.”
But eight million doses was the last significant shipment in years. From 2015 on, the US instead ordered hundreds of millions of dollars in bulk vaccine products – essentially raw vaccines stored in bulk bags, which would be converted to freeze-dried doses after The company perfects the process and has the required FDA. approve.
By 2017, all 27,993,370 doses in the national Jynneos stockpile had expired, although the United States still has a large stockpile of its other smallpox vaccines.
Nicole Lurie, who oversaw the stockpile during her eight-year tenure as assistant secretary for preparedness and response in the Department of Health and Human Services under President Barack Obama.
Both Jynneos and older reserve smallpox vaccines, such as ACAM2000, are good choices for making smallpox vaccines. Federal officials hoped ACAM2000 would protect against monkeypox and shipped doses for local health authorities to useBut its harsher side effects made many doctors uncomfortable using it for a mass monkeypox vaccination campaign.
From this time to that time
The goal of producing a freeze-dried vaccine has taken longer than expected, in part because of the slow FDA review process. In recent years, the Bavarian Nordic has also undertaken an expansion that will eventually delay the delivery of doses of the vaccine.
Bavarian Nordic has long relied on outside companies for the final stages of production, such as filling the actual jars.
By 2017, the company plans to build its own “complete” facility to make its vaccine production “more profitable than we’ve seen in the past,” according to the executive. Bavarian Nordic, Paul Chaplin, with the US government. partially funded this expansion.
At the beginning of 2020, the United States ordered 1.4 million liquid frozen doses from Bavarian Nordic, the first major order for a ready-to-use product in years. About 372,000 of those doses have been filled and shipped back to the United States by a contractor in recent weeks. They used to the main source of dose for the country’s monkeypox vaccination program to date.
The rest is to be filled at the new Bavarian Nordic finishing facility, which will be operational in 2021.
But the FDA did not inspect the facility at the time of the monkeypox outbreak. As a result, the bulk of the 1.4 million dose order remained in Denmark until last month, when FDA inspectors arrived.
Now, the US government has asked Bavarian Nordic to start sending out as many doses as quickly as possible, dropping its goal of a freeze-dried formulation for the time being.
But it could be last month The company could supply millions more doses from the bulk vaccine supply the United States has paid Bavarian Nordic for years to store, US officials said.
With so few Jynneos on hand to prevent a monkeypox epidemic, federal officials are taking a fresh look at the expired drug they still have on hand. Health and Human Services officials sent the sample back to the Bavarian Nordic for testing.
Officials say it’s “very unlikely” they are still possible. But if that’s the case, the Strategic Preparedness and Response Administration, a division of HHS, said it would be “ready to respond”.
Sheryl Gay Stolberg contribution report.
