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

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

Compelling data from studies in monkeys and humans suggest that a single dose of the vaccine – manufactured by Bavaria Nordic and sold under three different brand names – protects strongly against monkeypox and that the second dose mainly serves to extend viability of protection.

The UK, Germany and Canada are offering the vaccine to anyone considered at high risk of infection – for now it’s mainly men who have sex with men (MSM) who have multiple partners. The United States initially limited the vaccine to contacts of confirmed cases, including health care workers, but on June 28 also began offering it to people at high risk of infection who had supposed exposures, which includes MSM who have had multiple partners “in an area where monkeypox is spreading.”

There is no way to put a hard number, but millions of people around the world are now eligible for the vaccine. However, there are not enough doses of the vaccine, which contains a virus called modified vaccinia Ankara (MVA), to quickly receive all of the two recommended doses, which are usually 4 weeks apart.

The UK is already giving people just one injection at the moment, advising them they may want the second dose if they have an 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 from establishing itself outside areas where it is already endemic.

Bavaria Nordic CEO Paul Chaplin, an immunologist, also embraces the single-dose plan. Studies have shown that the immune responses induced by a single shot of the MVA vaccine decline after 2 years, which is why the approved vaccine schedule requires a second shot. But Chaplin says the immune memory is so strong after a single dose that a booster given 2 years later leads to the same immune response as the standard schedule. If countries decide to use single pumps now, they have a long time to add the booster and still achieve the sustainability benefit, he believes. “There’s a lot of data to support the one shot,” says Chaplin.

Bernard Moss, a virologist at the US National Institute of Allergy and Infectious Diseases who studied the efficacy of a single-dose MVA vaccine in monkeys, says he’s reluctant to make recommendations for public health — let alone volunteers: “ I think a single dose in an emergency setting is reasonable.” The Centers for Disease Control and Prevention (CDC), however, says the United States will stick to the two-dose regimen because that’s what the Food and Drug Administration (FDA) has approved.

Growing explosion

More than 5,700 people in 66 countries have been affected by 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 some children.

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

One, called ACAM2000, is a modern version of the old smallpox vaccine, made from unmodified vaccinia virus, that helped eradicate the disease from humans, an achievement the WHO celebrated as complete in 1980. The FDA approved ACAM2000 in 2007, and the United States has enough in its National Strategic Stockpile (NSS) to vaccinate the entire nation’s population if there is a smallpox bioterror attack. Some of the vaccines were used “off label” for monkeypox in the current outbreak. But vaccinia replicates after vaccination, which can lead to serious illness, especially in people whose immune systems have been compromised by HIV, which has a high prevalence among MSM, or other factors.

MVA, the virus in the Nordic Bavarian vaccine, does not multiply 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 approved explicitly 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 protected animals from monkeypox.

In the United States, SNS will make 56,000 doses of Jynneos immediately available to states, officials said during a June 28 White House press conference. Because this is not nearly enough to meet potential demand, the government has created a four-tier distribution system that prioritizes localities with the highest rates of monkeypox and the largest high-risk populations. Officials said they expect to receive an additional 296,000 doses from Bavaria Nordic “in the coming days.”

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

Individual countries in Europe have also bought supplies of the vaccine, but numbers are difficult to confirm. Still, the world has about 1 million doses of the vaccine on hand, Chaplin says. Supply will increase steadily later this year. Bavaria Nordic already has an additional 1 million doses available for the United States, which still require the FDA’s blessing because they were produced at a new plant in Denmark, Chaplin says, and the U.S. government today announced the purchase of 2.5 million doses. others to be submitted. until the beginning of 2023.

But the supply of the vaccine to prevent monkeypox today “remains very limited,” said a June 15 WHO guidance on monkeypox, which encourages countries that have doses to share them with those that do. limited or not at all.

Restrictions are being intensified 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 occupation: health care workers, outbreak response teams and laboratory workers who might handle viral samples. The other was persons 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. Now, some countries are effectively offering the vaccine as pre- and post-exposure prophylaxis for anyone at high risk.

At a press conference this week announcing US plans to expand vaccination, CDC Director Rochelle Walensky stated that two doses of MVA are needed since “it takes about 2 weeks after the second dose for maximum protection.”

Faster protection

In a study published in New England Journal of Medicine in 2019, Chaplin and colleagues compared immune responses in people given MVA or ACAM2000. With smallpox virus, levels of neutralizing antibodies are seen as a key indicator of protection, so the same idea extends to monkeypox virus. The researchers found that 14 days after a single dose, monkeypox-neutralizing antibody levels peaked with MVA, at a level nearly identical to that induced by ACAM2000. Given that vaccines are supposed to work after exposure if given within 2 weeks of contact, 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 vaccination against monkeypox by a single dose of MVA and a dose of a more crude version of ACAM2000 called Dryvax. Because MVA does not make copies of itself, the team gave it at a higher dose — similar to what is used today in the Nordic Bavarian vaccine — than the Dryvax vaccine.

Both vaccines worked well, but MVA seemed to work faster. Levels of neutralizing antibodies and CD8 cells — critical immune players that destroy infected cells — both rose faster with MVA, which Moss and colleagues concluded was because it took time for Dryvax to replicate to levels matching the stroke. initial MVA. Furthermore, when they injected the animals with the monkeypox virus just 4 days after vaccination, it grew less in the MVA-vaccinated monkeys.

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

At this week’s press conference, there was no discussion of temporarily giving only one dose in the US vaccination campaign. But when asked about the option from sciencePeter Marks, head of the FDA’s vaccine division, said “we are looking into this.”

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