Katelyn Jetelina and Caitlin Rivers, PhD

11 hr ago

Monkeypox (MPX) cases continue to increase in the United States and across the globe. Concurrently, the availability of the best vaccine option— Jynneos—is constrained. As Bloomberg reported Wednesday, the Jynneos manufacturer isn’t certain it can meet demand. The U.S. has bought some time by switching to a dose-sparing strategy that involves giving the vaccine intradermally, but it’s important we have a plan for what to do if this isn’t enough supply. It’s time to start the tough discussion about whether and how to use ACAM2000.

ACAM2000

ACAM2000 is a second-generation smallpox vaccine that was licensed in 2007. Because MPX is genetically so closely related to smallpox, we can use this vaccine for the current outbreak.

ACAM2000 is a “replication-competent vaccine,” which means it uses live, infectious virus. The vaccine does not contain variola (the virus that causes smallpox), so the vaccine cannot cause smallpox. Instead, it contains vaccinia virus, which is in the same family as smallpox but causes milder disease.

ACAM2000 is administered differently from the vaccines we’re used to. Instead of a regular needle, it’s administered with a two-pronged (bifurcated) needle that’s dipped into vaccine solution. The skin is pricked multiple times with drops of the vaccine. After 3-5 days, the vaccination site develops into a red, itchy sore spot which must be kept covered. The blister then dries up, forming a scab that falls off around week 2 or 3. This leaves a small, pitted scar.

Benefits and risks
Right now, Jynneos is the main vaccine being used to prevent monkeypox. But if the epidemic continues to grow, health officials may face tough choices about whether to add ACAM2000, which is already available for order from the stockpile. However, rolling it out is not as simple as it may seem on the surface. There are benefits and risks that need to be carefully weighed:

Benefits

Effective. We have plenty of clinical trials and real world evidence showing that ACAM2000 is effective against smallpox. Lab data, as well as some limited real-world evidence, suggest that ACAM2000 is also effective against MPX. A 1988 study in the Democratic Republic of the Congo found that a vaccinia-based vaccine was 85% effective in preventing monkeypox, which is promising but outdated.

Plentiful. The Strategic National Stockpile contains over 100 million doses of the vaccine, which could be immediately put to use. Increasing vaccination coverage would extend protection to more people and potentially slow the epidemic.

Reserves Jynneos for certain populations. There are several groups of people who can receive Jynneos but not ACAM2000, including people who are pregnant, have skin conditions like eczema, or people with weakened immune systems (including people living with HIV, especially if they are not receiving treatment). Adopting a strategy that uses both vaccines could reserve supply of Jynneos for people who are not eligible to receive ACAM2000.

Risks

Transmission risk. ACAM2000 contains live, infectious virus. If the vaccination site is not properly cared for, vaccinia virus can spread to other parts of the body—or even to other people. This means that unvaccinated people could be accidentally infected by someone who recently received the vaccine. For people with underlying medical conditions, vaccinia infection through close contact with someone recently vaccinated can result in serious illness.

Safety. ACAM2000 can cause myocarditis and pericarditis (heart inflammation). Based on clinical studies, this occurs 1 in 175 adults who get the vaccine for the first time.

More supply needed. Before this outbreak, the CDC recommended that people administering ACAM2000 be offered a vaccine. There are thousands of public health and medical workers administering vaccines. This will put more strain on supply.

The best system we have in place to weigh the benefits and risks is through external scientific advisory committees: VRBPAC and ACIP. If asked to convene, independent experts on those committees would review the available data and consider the benefits and risks (including many I’m sure we haven’t thought of in this post). Importantly, they would also have a robust discussion and debate in a public forum, which is just what we need. If the benefits don’t outweigh the risks right now, the committees can define a future threshold where the balance may tip.

Bottom line

As with every vaccine, we must weigh benefits with risks. There may come a point where the supply of Jynneos is not able to meet demand, turning attention to ACAM2000. We should act ahead of time (now!) to plan for that scenario. Plan for the worst, and hope for the best.

Love, YLE and Dr. Caitlin Rivers

Caitlin Rivers, PhD, MPH 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. She recently coauthored an op-ed on the use of ACAM2000 for the monkeypox outbreak. And she has her own newsletter called Force of Infections:

“Your Local Epidemiologist (YLE)” is written by Dr. Katelyn Jetelina, MPH PhD—an epidemiologist, biostatistician, wife, and mom of two little girls. During the day she works at a nonpartisan health policy think tank, and at night she writes this newsletter. Her main goal is to “translate” the ever-evolving public health science so that people will be well equipped to make evidence-based decisions. This newsletter is free thanks to the generous support of fellow YLE community members.

Illustration: Health officer inspecting people for smallpox vaccination scars, Newark, New Jersey, 1931. Bettmann Archive/Getty Images