FDA needs to fully review ACAM2000 before allowing its widespread use as a monkeypox vaccine

As the United States grapples with monkeypox, which has been declared a public health emergency, one of the key strategies that will be used to control its spread is vaccinating high-risk individuals.

Demand for monkeypox vaccine far exceeds the supply.

When the outbreak began, the U.S. Strategic National Stockpile held a small supply of Jynneos, a vaccine licensed for monkeypox. The federal Administration for Strategic Preparedness and Response has allocated more than 1 million doses of Jynneos to state and local jurisdictions, yet full coverage of those at highest risk would require an estimated 3.2 million doses. Bavarian Nordic, the company that makes Jynneos, isn’t expected to be able to manufacture additional doses in the near term.

As the Washington Post has reported, the shortfall has increased external pressure on the Biden administration to turn to another vaccine, ACAM2000, to close the gap.

The Food and Drug Administration licensed ACAM2000 in 2007 to immunize people at high risk of smallpox infection. There is moderate evidence the vaccine will also work against monkeypox, which is closely related to smallpox.

More than 100 million doses of ACAM2000 were added to the Strategic National Stockpile in the years after the Sept. 11 and anthrax attacks as a hedge against the return of smallpox. Unlike Jynneos, which is not capable of replicating in the human body, ACAM2000 contains live, replication-competent vaccinia virus. Vaccinia is a pox family virus related to smallpox that cannot cause smallpox and leads to milder disease.

If the vaccination site is not cared for properly for the two to six weeks it takes to heal, the vaccinia virus can spread to other parts of the body, including the eyes and genitals.

It is not just the vaccine recipient who is at risk after ACAM2000 inoculation. Household members and others who come into close contact with the recipient are also at risk of developing vaccinia infection. This has special relevance to the current outbreak.

Gay, bisexual, and other men who have sex with men are currently at highest risk of monkeypox infection. They are also disproportionately affected by HIV, which can compromise the immune system if not properly treated. Although it seems unlikely that people living with HIV would be offered ACAM2000 because of the risk of adverse events, vaccinia transmission from a vaccinated person to someone with a compromised immune system is a serious risk. Other risks of ACAM2000 include myocarditis (inflammation of the heart muscle) or pericarditis (inflammation of the sac surrounding the heart), which occur in about 1 in every 175 recipients. Generalized or widespread vaccinia infection can also occur. Although the heart conditions and vaccinia infection are uncommon, they are potentially deadly.

These risks make sense in the context of smallpox, which is more transmissible and more deadly than monkeypox. ACAM2000 is highly effective in preventing smallpox infection and, if smallpox were to reemerge, the protection would far outweigh the risks of ACAM2000 vaccination. For monkeypox, though, the balance of risks and benefits is less favorable.

If demand for vaccines to fight monkeypox grows beyond the supply of Jynneos, officials may begin to turn to ACAM2000. The recent decision to stretch the supply of Jynneos by allowing the use of lower doses may decrease pressure to use ACAM2000 in the near term, but if the epidemic continues to grow, calls for ACAM2000 use may intensify.

Health departments can now order this vaccine from the Strategic National Stockpile to use in the monkeypox response through an existing Expanded Access Investigational New Drug application, and at least one jurisdiction has already requested this product for potential use against monkeypox.

Although swift and decisive action is imperative to contain the current outbreak, the risks of ACAM2000 require a more deliberative approach. Before making the vaccine more widely available, the FDA should review the available evidence on its safety and effectiveness for preventing monkeypox and present those findings to the Vaccine and Related Biological Products Advisory Committee (VRBPAC). If the FDA and VRBPAC experts recommend the use of ACAM2000, the CDC’s Advisory Committee on Immunization Practices (ACIP) should meet to consider its appropriate use.

Evaluation by these two committees is the standard process for licensing vaccines and recommending them for use in clinical practice. Both committees are staffed by independent experts and the proceedings are open for public viewing and comment. Although it is not required in this instance, leveraging those resources would lend transparency and credibility to a difficult and complex decision.

The monkeypox epidemic is a serious and fast-moving crisis that shows no signs of coming under control. Public health officials should consider all options for protecting people at risk while ending domestic transmission. However, we believe that the risks of ACAM2000 are too serious in this setting to deploy the vaccine without the usual expert review governing the use of new vaccines. Existing review processes at VRBPAC and ACIP can be adapted to ensure that the risks and benefits of ACAM2000 are carefully considered before it is made available to members of the public.

Caitlin Rivers is a senior scholar and epidemiologist at the Johns Hopkins Center for Health Security, and served as the founding associate director of the Center for Forecasting and Outbreak Analytics at the Centers for Disease Control and Prevention. Tom Inglesby is an infectious disease physician, director of the Johns Hopkins Center for Health Security, and a former senior adviser to the Biden administration’s White House Covid-19 Response Team.