Two vaccines are available for monkeypox. Vaccine expert Agam Rao, MD, medical officer in CDC's Poxvirus and Rabies Branch, answers questions about their effectiveness and dosing.
How effective is the smallpox vaccine against monkeypox, and how was it identified as potentially protective against monkeypox?
Smallpox is the illness that is caused by variola virus, a member of the genus Orthopoxvirus. Monkeypox virus is in that same genus. For viruses within the same genus, we expect that a vaccine against one will be effective against the other.
There are actually several different vaccines worldwide that are used for smallpox and other similar viruses. In the United States, we have two vaccines that are licensed for the prevention of smallpox: ACAM2000 and JYNNEOS. JYNNEOS happens to be licensed by the US Food and Drug Administration (FDA) for prevention of monkeypox as well.
We don't have any reason to believe that either of these vaccines would differ in effectiveness for monkeypox vs smallpox because the two viruses are related.
Do you have any data on how effective ACAM2000 and JYNNEOS are in preventing smallpox?
JYNNEOS is a new vaccine and therefore was not used during the eradication campaign for smallpox, so we don't have any real-world data on how effective it would be in preventing smallpox.
In terms of ACAM2000, its precursor, a drug called Dryvax, was used during the eradication campaign, and data indicated that it was 85% effective at preventing smallpox if it was given as postexposure prophylaxis within 4 days of an exposure. Even beyond that, if the drug was given up to 14 days after an exposure, it would then at least lessen the symptoms.
We don't have data about the real-world effectiveness of these vaccines to prevent monkeypox, particularly in this outbreak.
Have there been monkeypox cases in older individuals who had been given the smallpox vaccine?
There have been cases of people who have gotten monkeypox despite being vaccinated as children or being vaccinated in the past. Vaccine effectiveness probably wanes over time.
We are also aware of monkeypox cases in people who had received the JYNNEOS or ACAM2000 vaccine as part of the current outbreak. There's really no vaccine that's 100% effective. There are always going to be people who don't mount an appropriate immune response, either because they're immunocompromised or for any other reason.
What data did the FDA look at to approve JYNNEOS for the prevention of smallpox and monkeypox?
In addition to the FDA approving the vaccine, the Advisory Committee on Immunization Practices, which is a group of vaccine experts who assemble to provide guidance to the CDC director for national vaccine recommendations, also recommended the JYNNEOS vaccine for the prevention of Orthopoxvirus infection for people with occupational risk. This was in November of last year and was unrelated to the current outbreak.
They reviewed data that indicate that JYNNEOS was noninferior to ACAM2000 when it comes to the immune response that healthy people had after they received it. The safety considerations were also favorable in comparison to ACAM2000.
What is the CDC doing to determine how effectively the JYNNEOS vaccine protects against monkeypox?
We are rolling out a lot of vaccine effectiveness studies in various stages. The team that has been leading that effort has been proposing studies to various health departments. We're also thinking of ways to interview vaccine recipients to understand whether people who got the vaccine are getting the infection. This would be individuals who have received both doses of the JYNNEOS vaccine.
Have these interviews already started?
Not yet. It takes some time to figure out the methodology: what questions would make sense, the number of people included, and where would be a good place to conduct these interviews. They've been pitched to some specific areas and those places are very interested. We're taking it step by step. We hope to be able to have data within a month.
How can the smallpox vaccine help to abate monkeypox, and can it eradicate monkeypox as it once did smallpox?
Smallpox and monkeypox are different infections for a few reasons. Monkeypox is a zoonotic disease. What that means is that the virus lives in other animals and moves to humans. Variola virus, which causes smallpox, is really only spread from person to person, and it doesn't really live in another animal. With smallpox, we basically had to eradicate the illness in only humans. It took a lot of effort, a lot of planning, and just amazing work. It is really an amazing success story.
The challenge with monkeypox virus is that there are animals, probably small mammals in certain countries in central and west Africa, that are reservoirs — constant sources — of this virus. That makes it a lot harder to eliminate. We don't know which animals are the reservoirs, despite a lot of testing.
Is there any evidence that monkeypox has been transferred to any animals outside of Africa during the current outbreak?
There was a report in The Lancet in the past month of possible spread to a dog in France. This is the first known case in a dog and it's unknown if the dog could further spread the infection.
We have guidance on our CDC website about how to prevent spread to people's pets and spread to people's family members. The fewer people and animals infected, the better — and the less chance of it being a problem.
What is the evidence in the literature for using the intradermal dosing strategy recently approved by the FDA?
There's a publication by Dr Sharon Frey in the journal Vaccine that describes the immune response in people who've received the intradermal JYNNEOS vaccine compared with people who received the subcutaneous dose. In that study, patients had a similar immune response whether the dose was given intradermally or subcutaneously. Also, the scientific community has experience with other intradermal administration of vaccines. It's not a technique that is commonly used in the United States, but internationally there are several different vaccines that are administered intradermally. There are data about intradermal use resulting in an equally robust or possibly even a more robust response than a subcutaneous vaccine. So the data are certainly there for intradermal vaccines. The challenge is that it's not a common route of vaccination in the United States, so it requires a steep learning curve.
How long would it take to develop a monkeypox-specific vaccine, and is there anyone working on that?
The actual virus used in vaccines to protect against orthopoxviruses is called vaccinia virus. There's nothing specific to smallpox about that virus. It's just another virus in the Orthopoxvirus genus that can be turned into a vaccine. The vaccina virus vaccine should be effective against any virus in the group, including monkeypox.
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Monkeypox Vaccines: Q&A With the CDC's Agam Rao, MD
COMMENTARY
Monkeypox Vaccines: Q&A With the CDC's Agam Rao, MD
Agam Rao, MD
DisclosuresSeptember 02, 2022
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Two vaccines are available for monkeypox. Vaccine expert Agam Rao, MD, medical officer in CDC's Poxvirus and Rabies Branch, answers questions about their effectiveness and dosing.
How effective is the smallpox vaccine against monkeypox, and how was it identified as potentially protective against monkeypox?
Smallpox is the illness that is caused by variola virus, a member of the genus Orthopoxvirus. Monkeypox virus is in that same genus. For viruses within the same genus, we expect that a vaccine against one will be effective against the other.
There are actually several different vaccines worldwide that are used for smallpox and other similar viruses. In the United States, we have two vaccines that are licensed for the prevention of smallpox: ACAM2000 and JYNNEOS. JYNNEOS happens to be licensed by the US Food and Drug Administration (FDA) for prevention of monkeypox as well.
We don't have any reason to believe that either of these vaccines would differ in effectiveness for monkeypox vs smallpox because the two viruses are related.
Do you have any data on how effective ACAM2000 and JYNNEOS are in preventing smallpox?
JYNNEOS is a new vaccine and therefore was not used during the eradication campaign for smallpox, so we don't have any real-world data on how effective it would be in preventing smallpox.
In terms of ACAM2000, its precursor, a drug called Dryvax, was used during the eradication campaign, and data indicated that it was 85% effective at preventing smallpox if it was given as postexposure prophylaxis within 4 days of an exposure. Even beyond that, if the drug was given up to 14 days after an exposure, it would then at least lessen the symptoms.
We don't have data about the real-world effectiveness of these vaccines to prevent monkeypox, particularly in this outbreak.
Have there been monkeypox cases in older individuals who had been given the smallpox vaccine?
There have been cases of people who have gotten monkeypox despite being vaccinated as children or being vaccinated in the past. Vaccine effectiveness probably wanes over time.
We are also aware of monkeypox cases in people who had received the JYNNEOS or ACAM2000 vaccine as part of the current outbreak. There's really no vaccine that's 100% effective. There are always going to be people who don't mount an appropriate immune response, either because they're immunocompromised or for any other reason.
What data did the FDA look at to approve JYNNEOS for the prevention of smallpox and monkeypox?
In addition to the FDA approving the vaccine, the Advisory Committee on Immunization Practices, which is a group of vaccine experts who assemble to provide guidance to the CDC director for national vaccine recommendations, also recommended the JYNNEOS vaccine for the prevention of Orthopoxvirus infection for people with occupational risk. This was in November of last year and was unrelated to the current outbreak.
They reviewed data that indicate that JYNNEOS was noninferior to ACAM2000 when it comes to the immune response that healthy people had after they received it. The safety considerations were also favorable in comparison to ACAM2000.
What is the CDC doing to determine how effectively the JYNNEOS vaccine protects against monkeypox?
We are rolling out a lot of vaccine effectiveness studies in various stages. The team that has been leading that effort has been proposing studies to various health departments. We're also thinking of ways to interview vaccine recipients to understand whether people who got the vaccine are getting the infection. This would be individuals who have received both doses of the JYNNEOS vaccine.
Have these interviews already started?
Not yet. It takes some time to figure out the methodology: what questions would make sense, the number of people included, and where would be a good place to conduct these interviews. They've been pitched to some specific areas and those places are very interested. We're taking it step by step. We hope to be able to have data within a month.
How can the smallpox vaccine help to abate monkeypox, and can it eradicate monkeypox as it once did smallpox?
Smallpox and monkeypox are different infections for a few reasons. Monkeypox is a zoonotic disease. What that means is that the virus lives in other animals and moves to humans. Variola virus, which causes smallpox, is really only spread from person to person, and it doesn't really live in another animal. With smallpox, we basically had to eradicate the illness in only humans. It took a lot of effort, a lot of planning, and just amazing work. It is really an amazing success story.
The challenge with monkeypox virus is that there are animals, probably small mammals in certain countries in central and west Africa, that are reservoirs — constant sources — of this virus. That makes it a lot harder to eliminate. We don't know which animals are the reservoirs, despite a lot of testing.
Is there any evidence that monkeypox has been transferred to any animals outside of Africa during the current outbreak?
There was a report in The Lancet in the past month of possible spread to a dog in France. This is the first known case in a dog and it's unknown if the dog could further spread the infection.
We have guidance on our CDC website about how to prevent spread to people's pets and spread to people's family members. The fewer people and animals infected, the better — and the less chance of it being a problem.
What is the evidence in the literature for using the intradermal dosing strategy recently approved by the FDA?
There's a publication by Dr Sharon Frey in the journal Vaccine that describes the immune response in people who've received the intradermal JYNNEOS vaccine compared with people who received the subcutaneous dose. In that study, patients had a similar immune response whether the dose was given intradermally or subcutaneously. Also, the scientific community has experience with other intradermal administration of vaccines. It's not a technique that is commonly used in the United States, but internationally there are several different vaccines that are administered intradermally. There are data about intradermal use resulting in an equally robust or possibly even a more robust response than a subcutaneous vaccine. So the data are certainly there for intradermal vaccines. The challenge is that it's not a common route of vaccination in the United States, so it requires a steep learning curve.
How long would it take to develop a monkeypox-specific vaccine, and is there anyone working on that?
The actual virus used in vaccines to protect against orthopoxviruses is called vaccinia virus. There's nothing specific to smallpox about that virus. It's just another virus in the Orthopoxvirus genus that can be turned into a vaccine. The vaccina virus vaccine should be effective against any virus in the group, including monkeypox.
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Cite this: Monkeypox Vaccines: Q&A With the CDC's Agam Rao, MD - Medscape - Sep 02, 2022.
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Authors and Disclosures
Authors and Disclosures
Author
Agam Rao, MD
Medical Officer, Poxvirus and Rabies Branch, Centers for Disease Control and Prevention, Atlanta, Georgia
Disclosure: Agam Rao, MD, has disclosed no relevant financial relationships.