Safety and effectiveness of the Jynneos monkeypox vaccine


I’m probably going to have to write about the safety and effectiveness of the monkeypox vaccine several times in the future. But I’ve been reading a lot of misinformation about the new vaccine (I’m shocked, are you?), so I thought I would write about what we know as of today.

Believe it or not, we know a lot about the vaccine. It has been through clinical trials, so we have as much information about the vaccine’s safety and effectiveness as we knew at the launch of every other vaccine. Despite the claims of vaccine deniers all over the world, clinical trials provide us with a lot of good information about vaccines.

Let’s take a look at what we know today about the safety and effectiveness of the monkeypox vaccine.

About monkeypox and the vaccine

Just as a refresher, monkeypox is caused by the monkeypox virus which is a double-stranded DNA, zoonotic virus. It is one of the human orthopoxviruses that includes variola (smallpox), cowpox, and vaccinia viruses. But it is not a direct ancestor to, nor a direct descendant of, the variola virus which causes smallpox. Monkeypox virus causes a disease that is similar to smallpox but with a milder rash and lower death rate.

The monkeypox virus is endemic to the tropical rainforests of West Africa and is found in primates and some other animals, such as the Gambian pouched rat. Despite the name, monkeypox isn’t a disease specifically associated with monkeys.

According to the CDC, symptoms begin with fever, headache, muscle pains, swollen lymph nodes, and feeling tired. This is followed by a rash that forms blisters and crusts over. The time from exposure to onset of symptoms is around 10 days. The duration of symptoms is typically two to four weeks. The symptoms are similar to chickenpox, although the Varicella zoster virus that causes chickenpox is not related to the monkeypox virus.

Transmission of monkeypox virus occurs when a person comes into contact with the virus from an animal, human, or materials contaminated with the virus. The virus enters the body through broken skin (even if not visible), respiratory tract, or mucous membranes (eyes, nose, or mouth). Human-to-human transmission is thought to occur primarily through large respiratory droplets, but much of the current outbreak appears to be from sexual contact, and may eventually be considered a sexually transmitted disease (STD).

The mortality rate for the disease ranges from 1% to 10%, depending on the variant (yes, we’ll be talking about variants again).

Monkeypox can be treated with anti-viral medications such as cidofovir. There may be other anti-viral drugs that can be used, but they have not been tested against this disease as of this time. You can bet there will be a lot of published articles on new drugs for monkeypox in the next few months.

As of 22 August 2022, the CDC reports that the current outbreak has caused 15,433 cases in the U.S., striking every state. The CDC also reports that as of 22 August 2022, there have been nearly 43,000 cases worldwide.

There is one vaccine, JYNNEOS (known as Imvamune in Canada and Imvanex in the EU) is an attenuated live virus vaccine, manufactured by Bavarian Nordic, that the U.S. FDA has approved for the prevention of monkeypox.

Monkeypox vaccine effectiveness

I have written about the monkeypox vaccine effectiveness previously. The number that’s been frequently quoted by media organizations is “85% effective” or “at least 85% effective.” But when I dig into that number, it is based on one small study done in Africa in the 1980s that has major limitations. Most of the other studies have only been conducted on animals, and unless you don’t read any of my articles, you would know that I take animal studies with a grain of salt.

I even got fooled by this 85% effectiveness when I wrote about the vaccine just a few weeks ago.

According to the CDC, there is “no data are available yet on the effectiveness of these vaccines in the current outbreak.” The CDC is generally careful about how they describe new vaccines, but that’s a pretty clear description of the vaccine.

As I discussed previously, the claims of 85% effectiveness of the monkeypox vaccine are based on a small study, a retrospective analysis published in September 1988 in the International Journal of Epidemiology.

In that study, researchers tracked the household contacts of 209 people infected with monkeypox in Zaire in the early 1980s. Those with scars from previous smallpox vaccination (70%) were 85% less likely to be infected. The vaccine seemed to be 89% effective at protecting contacts outside the household from infection. This is a small retrospective cohort study, not a large randomized, double-blind clinical trial.

There are no other data that show whether the vaccine has any level of effectiveness against the virus. And this study was done based on the older smallpox vaccine, which many of us got in the 1960s and 70s, and not with the new JYNNEOS vaccine.

The problem with trying to determine the effectiveness of this vaccine is that monkeypox wasn’t widespread at the time of approval, so numbers are so low that it makes statistical analysis almost impossible.

JYNNEOS has not been tested against smallpox or monkeypox in clinical trials. Now there are a couple of reasons for this — smallpox is essentially eradicated from the planet and monkeypox wasn’t endemic until recently. There is a large body of animal studies that support the effectiveness of the vaccine, but not in humans. Many scientists roll their eyes at animal studies that have not been confirmed by clinical trials. I’m one of those.

But there’s one more issue that could be problematic. These vaccines were developed based on the assumption of skin-to-skin contact like we used to see with smallpox a generation or two ago.

The current monkeypox outbreak appears to be mostly sexually transmitted— the head of the penis and interior of the anus may have characteristics that make them more susceptible to infection such as a lower dose of virus needed, less abundant antibodies or other components of the immune system, or concurrent STDs increasing risk. This may not be a concern, but we won’t know until there is adequate testing.

In the JYNNEOS package insert, Bavarian Nordic did not determine vaccine effectiveness directly. They inferred it from comparing immunogenicity between their vaccine and the older ACAM2000 along with animal challenge studies. I presume that real-world effectiveness will become available in a few months as researchers monitor the vaccinated population.

This chart seems to indicate a pretty strong neutralizing antibody response for JYNNEOS compared to ACAM2000:

I’m pretty confident that the effectiveness of the monkeypox vaccine will be quite high, but I don’t have evidence to back up that statement

Monkeypox vaccine safety

To be blunt, we don’t have good data on the vaccine’s safety profile, except for what was submitted to the FDA. But I want to back up a bit because I know that there is some misinformation out there about this vaccine, much of it based on the history of the vaccine.

Smallpox was eradicated as a result of Dryvax, a live virus vaccine made using a smallpox virus relative called vaccinia. Although it was very effective (we eradicated the disease with it), the vaccine had some nasty side effects.

In 2007, Dryvax was replaced by a safer and equally effective alternative called ACAM2000, which had good protective effects not only against smallpox but also against monkeypox. ACAM2000 used a live virus, like Dryvax, that could reproduce inside human cells — nearly 1 in 175 people who received the vaccine developed an inflammatory heart condition called myocarditis (treatable and not usually lethal, but still, not great to have).

Some people are pushing a narrative that these safety issues still exist with the Jynneos vaccine. Nothing could be further from the truth.

As I discussed above, Jynneos also uses a live virus — modified vaccinia Ankara (MVA) — that elicited a potent protective response without being able to reproduce in human cells. Since it is unable to reproduce, its safety profile is substantially better than Dryvax or ACAM2000.

According to the Jynneos package insert, the clinical trial program included 22 studies and a total of 7,859 individuals 18 through 80 years of age who received at least 1 dose of JYNNEOS (7,093 smallpox vaccine-naïve and 766 smallpox vaccine-experienced individuals). This is a fairly robust set of clinical trials.

Minor adverse effects were:

 Of course, most of you aren’t too concerned with minor side effects since they happen with almost every new vaccine. We saw the same kind of results from the initial clinical trials for the COVID-19 vaccines.

Again, according to the package insert, serious adverse events (SAE) were reported for 1.5% of JYNNEOS recipients and 1.1% of placebo recipients. That’s a small, probably not statistically significant difference between the groups.

However, cardiac adverse events of special interest (AESI) were reported to occur in 1.3% (95/7,093) of JYNNEOS recipients and 0.2% (3/1,206) of placebo recipients who were smallpox vaccine-naïve. Cardiac AESIs were reported to occur in 2.1% (16/766) of JYNNEOS recipients who were smallpox vaccine-experienced.

Of the 95 cardiac AESIs, six cases (0.08% of the total vaccinated population) were considered to be causally related to JYNNEOS vaccination and included tachycardia, electrocardiogram T wave inversion, electrocardiogram abnormal, electrocardiogram ST segment elevation, electrocardiogram T wave abnormal, and palpitations.

None of those cardiac AESIs were considered to be serious issues and did not threaten the lives or long-term health of the participants.

Summary of monkeypox vaccine safety and effectiveness

We have a lot of information about monkeypox vaccine safety and some information about effectiveness from the rather large and robust clinical trials. Clearly, we need more information about the effectiveness of the JYNNEOS vaccine against monkeypox, but I’m sure that’s forthcoming.

Digging into this article, I was surprised by how much information there was in FDA documents about the safety and effectiveness of the JYNNEOS smallpox and monkeypox vaccine.

I think the safety issues with cardiac events will be monitored closely as more individuals get the vaccine, but as of today, those issues seem very minor (though if it happened to you, I’m sure you’d be scared).

Stay tuned — there will be more and more information available as more and more people get the vaccine.

Citations

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