Animal research

Monkeypox :: Understanding animal research

What is monkey pox?

Monkeypox is a disease caused by an orthopox virus, the family of viruses that includes smallpox. Monkeypox is a viral zoonotic infection, which means it can spread from animals to humans. It can also spread from person to person. Monkeypox is spread through close contact with someone who has a monkeypox rash, including face-to-face, skin-to-skin, mouth-to-mouth, or mouth-to-skin contact, including sexual contact. In most cases, symptoms last two to three weeks and usually resolve on their own or with medical treatment. In some cases, the monkeypox virus can be fatal.

Monkeypox is of particular concern for newborns, young children, and people with underlying immune deficiencies, as these people may be at risk for more severe and even fatal symptoms.

People who have been vaccinated against smallpox may have some protection against monkeypox due to the close resemblance of the viruses. However, routine smallpox vaccination stopped in most places after its eradication in 1980.

For more information on symptoms, transmission, and general information on what to do if you get monkeypox, go to the World Health Organization website.

The first case of monkeypox

The monkeypox virus was first documented in Denmark in 1958 during an outbreak in research monkeys (cynomolgus macaques) that were used for polio vaccine-related research. These monkeys are believed to have caught the virus from a source in Africa before being transported to Denmark.

Despite its name, which suggests that monkeys are the original host of the virus, scientists have yet to identify the specific animal reservoir of monkeypox. To date, monkeypox has been found in many animal species, including squirrels, Gambian giant rats, striped mice, dormice and primates.

The first recorded case of monkeypox in humans occurred in the Democratic Republic of the Congo (then Zaire) in 1970, and all subsequent cases to date have been linked to the spread of the virus from animals in Africa.

Monkey pox research

Monkeypox research has primarily focused on reorienting vaccines and treatments developed to combat smallpox. At present, the smallpox vaccine is licensed for use as a preventive measure against monkeypox in the UK.

According to the UK government website, “Antiviral medicines such as cidofovir and tecovirimat can be used to treat monkeypox patients with severe disease or those at high risk of severe disease. Vaccination against smallpox can be used both before and after exposure and is up to 85% effective in preventing monkeypox.” We will update this webpage with more information about the animal research behind these drugs in due course.

Smallpox and the smallpox vaccine

Smallpox is a fatal disease caused by the smallpox virus, it is part of the orthopox family of viruses, the same family of viruses as monkeypox. Smallpox is the only disease we have managed to eradicate from the Earth, thanks to widespread vaccination. Before the eradication of smallpox, one in ten people died from it and one in four people were paralyzed or disfigured after surviving the initial illness.

Since smallpox and monkeypox come from the same family of viruses, they are genetically similar, which means that the smallpox vaccine confers some immunity against monkeypox. At present, it is one of our main methods of defense against monkeypox.

The smallpox vaccine was the first successful vaccine to be developed by mankind and marks a major milestone in modern medical research. In 1798, Edward Jenner used people with smallpox to test and develop the smallpox vaccine. Human lymphatic tissue, taken from patients who were already immunized, was used to make the vaccine, but the occasional transmission of syphilis and the lack of human tissue available to fight an epidemic led to the use of animals to prepare the vaccine.

Various animal species have been used to create vaccine material (infected tissue), including horses, mules, goats, and rabbits. However, in the 1970s, calves were chosen as the most appropriate animal to use to prepare vaccine material. Rabbits were used to see how potent the prepared virus was, and mice were also used to ensure the absence of tetanus bacilli, before the advent of modern tetanus tests.

Animal research and monkeypox

Monkeypox is a zoonotic virus, which means it can jump from animals to humans. It has been found in a wide range of animals including rope squirrels, tree squirrels, Gambian rats, dormice and some species of monkeys. Due to the zoonotic nature of monkeypox, research has been conducted on both captive and wild animal populations. When dealing with zoonotic diseases, it is important that the reservoir or animal host be identified, in order to mitigate the spread of the disease. If we don’t know where the virus is coming from, we will have a hard time containing it. Unfortunately, the animal species that served as the original host for the virus has not yet been identified.

Imvanex vaccine

In the UK, EU and US, the main line of defense against monkeypox is the smallpox vaccine Imvanex (also known as JYNNEOS). At the time of publication, monkeypox vaccines have been offered to at-risk groups through the NHS. Because the two viruses share many similarities, the smallpox virus has so far been effective in controlling the spread of monkeypox.

Animal testing was needed before the Imvanex/JYNNEOS vaccine could be given to humans in clinical trials. This is a process that has been applied to almost all modern vaccines and is required by the Medicines Act 1968 and guided by Animals (Scientific Procedures) Act, 1986 . Other relevant laws can be found here.

Monkeys were used to test the effectiveness of the Imvanex vaccine in preventing smallpox. This is achieved through a challenge study which involves vaccinating the animal, waiting a specified interval to give the vaccine time to work, and “challenging” the vaccine by exposing the animal to what should be an amount deadly virus. Imvanex successfully protected all trial monkeys from death, including intravenous (injection) and intratracheal (inhalation) exposure. Monkeys were also used to determine the dose of vaccine needed for effective protection.

Part of the reason we know the smallpox vaccine works against monkeypox is because the vaccine was tested on monkeys in preclinical development. There are several viral diseases that have a primate version and a human version (such as HIV and SIV); monkeypox and smallpox are essentially the same virus but they each target a different species. In testing the effectiveness of Imvanex, monkeys were infected with monkeypox, which was considered sufficiently similar to smallpox to provide meaningful data.

Mice were also used to test the effectiveness of Imvanex through a challenge study and to determine the amount of vaccine needed to provide protection. The mice were challenged with vaccinia virus Western Reserve (VV-WR), a less lethal form of poxvirus.

Sources

https://www.who.int/news-room/questions-and-answers/item/monkeypox

https://www.ecdc.europa.eu/en/all-topics-z/monkeypox/factsheet-health-professionals

https://www.science.org/content/article/concern-grows-human-monkeypox-outbreak-will-establish-virus-animals-outside-africa

https://www.ema.europa.eu/en/documents/assessment-report/imvanex-epar-public-assessment-report_en.pdf

https://www.animalresearch.info/en/medical-advances/diseases-research/smallpox/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1200696/