Can prior smallpox infection or vaccine provide immunity to ampox?
The new ampox outbreak has spread outside of Africa, leading the World Health Organization to declare it a public health emergency of international concern. Although the smallpox vaccine provides some protection against ampox due to their genetic similarities, it is not completely safe.

In short
- WHO declares ampox a public health emergency
- Smallpox vaccine provides some protection
- Chickenpox vaccine ineffective against chickenpox
The new monkeypox (or ampox) outbreak has already reached other continents after being spotted in the Democratic Republic of Congo on the African continent. It emerged in 2022, but this time the virus strain is different from the previous one. This strain has recently jumped from animal to human and is called clade 1b.
The last strain, clade 1, died down in 10 months. The World Health Organization has warned the ampox outbreak is a public health emergency of international concern.
The ampox virus is also said to be a cousin of the smallpox virus. And because they are related in some ways, it is being said that the smallpox vaccine may provide some protection against the ampox virus as well.
While smallpox was officially eradicated in the US in 1972, it was eradicated in India in 1979. Since then, smallpox infections have been seen more frequently in unvaccinated people.
“There is no vaccine made specifically for the ampox virus. When the global ampox outbreak occurred in 2022, we were hoping that the smallpox vaccine could cross-protect against ampox,” said Dr Rajeev Jayadevan, infectious disease specialist and member of IMA Kochi.
Both ampox and smallpox are related to the vaccinia virus. The current smallpox vaccine is based on the vaccinia virus.
So, imagine there is virus A, virus B, and virus C. They have created a vaccine based on virus C that is intended to provide protection against A and B. In other words, a vaccine that provides cross protection against smallpox also provides cross protection against monkeypox.
Data from Western countries since the 2022 outbreak suggests that people who took the modern version of the smallpox vaccine (Geneios) had significantly reduced the number of cases of ampox.
Now let’s look at the case of someone who received the smallpox vaccine as a child. They would now be 45 years or older depending on the years in which the smallpox vaccine was discontinued. Theoretically these people might still have some protection, but the data on the ground does not fully support this theory.
There have been cases of many people who had already been vaccinated against smallpox getting infected with ampox. Perhaps the immunity acquired from the vaccine has waned after so many years. We can say that it may provide some cross protection, but it is not a completely safe protection.
“Chickenpox and ampox have no similarities except that the skin lesions look similar. In fact, one can be confused with the other. If someone has had chickenpox vaccine or infection, it does not provide any cross protection against ampox as they are completely different and unrelated viruses,” said Dr Jayadevan.
“Regarding vaccines for ampox, smallpox vaccines provide significant protection due to the close genetic relationship between the two viruses. Two vaccines are currently used. The smallpox vaccine (vaccinia virus vaccine) provides cross-protection against ampox due to the genetic similarity between the two viruses. This vaccine was originally developed to eradicate smallpox, and since both viruses belong to the same family, the immunity provided by the smallpox vaccine can actually reduce the severity of ampox or prevent it altogether,” said Dr. Giridhar Babu, epidemiologist, physician scientist, author on global health and infectious diseases.
He added, “However, the chickenpox vaccine, which is designed to protect against the varicella-zoster virus, is not related to mpox and therefore does not provide cross-protection. The varicella-zoster virus belongs to a completely different family of viruses (Herpesviridae) and does not provide immunity against orthopoxviruses such as mpox.”
On the potential impact of declaring ampox a public health emergency of international concern, Dr Babu said, “The recent surge in ampox cases, particularly the spread of new variants and their impact on both adults (mainly through sexual contact) and children, highlights the urgent need for vigilance and preparedness, especially as the population returns to school and other community spaces after the holidays.”