There is a shortage of monkeypox vaccine. Could one dose be enough instead of two? | Science

As the monkeypox epidemic grows, the preferred vaccine to combat it is in short supply, a problem that is only getting worse now that countries are expanding access to the vaccine. But there is a strategy that can double overnight the number of people who can be vaccinated: use one injection instead of the recommended two.

Convincing data from studies in monkeys and humans suggest that one dose of the vaccine, manufactured by Bavarian Nordic and sold under three different brand names, provides solid protection against monkeypox and that the second dose serves mainly to extend the duration of protection.

The UK, Germany and Canada offer the vaccine to anyone thought to be at high risk of infection – so far mostly men who have sex with men (MSM) who have multiple partners. The United States initially restricted the vaccine to contacts of confirmed cases, including healthcare workers, but on June 28 also began offering it to people at high risk of infection who have had supposed exposures, which included MSM who had multiple partners “in an area where monkeypox is endemic.”

There’s no way to put an exact figure, but millions of people around the world are already eligible for the vaccine. Still, there aren’t enough doses of the vaccine, which contains a virus called modified vaccinia Ankara (MVA), to give everyone the quickly recommended two doses, which are usually 4 weeks apart.

The UK is already giving people just one injection for now, advising them they may want the second dose if they are at ongoing risk. And some public health officials and scientists say time is of the essence for a broader vaccination campaign among high-risk people if countries hope to prevent the epidemic from spiraling out of control and the virus becoming established outside areas where it is already endemic .

Bavarian Nordic CEO Paul Chaplin, an immunologist, also accepts the single-dose plan. Studies have shown that immune responses induced by a single MVA vaccine wane after 2 years, so the approved vaccine schedule requires a second vaccine. But Chaplin says the immune memory is so stable after a single dose that a booster given 2 years later produces the same immune response as the standard regimen. If countries decide to use single shots now, they have plenty of time to add the booster and still achieve the endurance advantage, he believes. “There’s a lot of data to support the single shot,” says Chaplin.

Bernard Moss, a virologist at the US National Institute of Allergy and Infectious Diseases who has studied the efficacy of a single-dose MVA vaccine in monkeys, says he is reluctant to make public health recommendations, but also volunteers: “I think a dose in the emergency setting is reasonable. However, the Centers for Disease Control and Prevention (CDC) says the United States will stick with the two-dose regimen because it is approved by the Food and Drug Administration (FDA).

A growing outbreak

More than 5,700 people in 66 countries have been infected with monkeypox since the beginning of May, and the number continues to rise. According to the World Health Organization (WHO), the majority of confirmed cases are in MSM. But the virus has also affected other groups, including several children.

Bavarian Nordic’s product is one of two FDA-approved monkeypox vaccines. Both were developed to target their cousin, smallpox, but animal studies show that both also protect against monkeypox.

One, called ACAM2000, is a modern version of the century-old smallpox vaccine made from an unmodified vaccinia virus that helped eradicate the disease from humans, an achievement noted by the WHO as having been completed in 1980. The FDA approved ACAM2000 in 2007. , and the United States has enough of it in its Strategic National Stockpile (SNS) to vaccinate the country’s entire population if there is a smallpox bioterrorist attack. Some of the vaccine was used “off-label” for monkeypox in the current outbreak. But the vaccine is copied after vaccination, which can lead to serious illness, especially in people whose immune systems have been compromised by HIV – which is highly prevalent among MSM – or other factors.

MVA, the virus in the Bavarian Nordic vaccine, does not replicate in the body and is much safer, making it the vaccine of choice for the monkeypox outbreak. Known as Jynneos in the United States, Imvanex in Europe and Imvamune in Canada, MVA is the only vaccine that the FDA has specifically approved for monkeypox. Because monkeypox is so rare, the company had no human efficacy data when it applied for FDA approval; the agency granted its license in 2019 based in part on studies showing the vaccine protects animals from monkeypox.

In the United States, SNS will immediately provide states with 56,000 doses of Jynneos, officials said during a June 28 White House press conference. Because this was not enough to meet potential demand, the government created a four-tier allocation system that prioritized the places with the highest rates of monkeypox and the largest high-risk population. Officials said they expected to receive an additional 296,000 doses from Bavarian Nordic “in the coming days.”

The European Commission’s Health Preparedness and Emergency Response Authority has purchased 109,090 doses of the vaccine – only some of which are immediately available – and is also prioritizing places with high numbers of cases. (The first 5,300 doses were sent to Spain; Portugal, Germany and Belgium followed.)

Individual countries in Europe have also purchased supplies of the vaccine, but numbers are difficult to confirm. Overall, the world has about 1 million doses of the vaccine, Chaplin says. Supply will increase steadily later this year. Bavarian Nordic now has an additional 1 million doses available for the United States, which still require the FDA’s blessing because they are manufactured at a new plant in Denmark, Chaplin says, and the U.S. government today announced the purchase of another 2.5 million doses that will be delivered by early 2023.

But the supply of vaccine to prevent monkeypox today “remains very limited,” said WHO’s June 15 monkeypox guidelines, which encourage countries that have doses to share them with those that have limited or no supplies .

The restrictions are being tightened given the expanded eligibility for the vaccine. Initially, many countries followed WHO guidelines and offered vaccination to only two groups. One was people who were at high risk of infection because of their occupations: healthcare workers, outbreak response teams and laboratory workers who might handle viral samples. The other was people who had been in close contact with a known case; the vaccine can work after exposure, ideally if given within 4 days but up to 2 weeks after exposure. Several countries now effectively offer the vaccine as pre- and post-exposure prophylaxis to anyone at high risk.

At a press conference this week announcing U.S. plans to expand vaccination, CDC Director Rochelle Walensky said two doses of MVA are needed because “about 2 weeks after the second dose are needed for maximum protection.”

Faster protection

In a study published in The New England Journal of Medicine in 2019, Chaplin and colleagues compared immune responses in humans given MVA or ACAM2000. With smallpox, neutralizing antibody levels are seen as a key indicator of protection, so the same idea applies to monkeypox. The researchers found that 14 days after a single dose, levels of antibodies that neutralize monkeypox peaked with MVA, at a level almost identical to that induced by ACAM2000. Given that vaccines are supposed to work post-exposure if given within 2 weeks of exposure, this suggests that a single dose of MVA could prevent many cases of disease and slow spread.

In a 2008 monkey study led by Moss, published in Proceedings of the National Academy of Sciencesresearchers compared pre-exposure monkeypox vaccination of a single dose of MVA and a single dose of a more severe version of ACAM2000 called Dryvax. Because MVA doesn’t make copies of itself, the team gave it at a higher dose — similar to what’s used in the Bavarian Nordic shot today — than the Dryvax vaccine.

Both vaccines work well, but MVA seems to work faster. Levels of neutralizing antibodies and CD8 cells—critical immune players that destroy infected cells—both rose more quickly with MVA, which Moss and colleagues concluded was the time needed for Dryvax to replicate to levels that matched the initial injection. with MVA. What’s more, when they injected the animals with the monkeypox virus just 4 days after vaccination, it grew worse in monkeys vaccinated with MVA.

In a statement to ScienceThe CDC emphasized that a single dose of the vaccine has not been studied in any outbreak and cautioned that it is “challenging” to extrapolate from immune responses in earlier studies and protection in animal studies.

This week’s news conference did not discuss temporarily giving only one dose in the US vaccination campaign. But when asked about the option of SciencePeter Marks, head of the FDA’s vaccine division, said “we are looking into this.”

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