Monkeypox virus is a DNA virus belonging to the orthopox virus Genus. This genus includes other viruses such as camelpox, cowpox, raccoonpox, skunkpox, variola, and vaccinia. While monkeypox was first discovered in monkeys in 1958, rodents are known to be its natural reservoir, and humans and other primates are often adventitious hosts. Human infection was first detected in the Democratic Republic of the Congo in 1970. The two most common and most diverse lineages of monkeypox include the West African strain, which causes less severe infection, and the Central African or Congo Basin strain, which causes more severe infection.
Human infections can occur through contact with infected animals or humans. Human-to-human transmission can occur through contact with a skin lesion or large respiratory droplets. The incubation period can vary from 7 to 21 days, with most symptomatic cases being self-limiting. The most common symptoms are chills, malaise, and fever, followed by the development of a centrifugal rash on the soles of the feet and palms. Over the next 2 to 4 weeks, the rash changes from maculopapular to vesicular to pustular to crusting. In addition, monkeypox infections are often characterized by lymphadenopathy.
However, the recent outbreak of monkeypox suggested that the infection could also be asymptomatic with some asynchronous skin lesions. Most of them appeared in the rectal mucosa, oral mucosa and genitals, which are the contact points for sexual attitudes. This has led to a misdiagnosis of monkeypox, along with delayed treatment. Additionally, reports from Germany and Italy have raised concerns about whether monkeypox is a sexually transmitted disease. In addition, the increase in the number of monkeypox infections in endemic parts of Africa and non-endemic parts of the world may be due to a combination of factors. These factors include no mutual protection against orthopoxviruses as a result of the cessation of smallpox vaccination after its eradication in 1980, rapid global spread, and the impact of genetic changes.
A new review published in The Lancet Infectious Diseases aimed to describe the efficacy of vaccinia virus-based smallpox vaccines against the current monkeypox outbreak.
Preventing monkeypox with vaccines: a quick review. Image credit: Spotted Yeti/Shutterstock
effect of vaccination
Previous research has shown that orthopoxviruses can recognize each other and provide protection depending on how closely related they are. It has been speculated that the cessation of smallpox vaccination may have led to an increase in monkeypox infections. The immunological cross-reactivity between the two viruses is due to high sequence similarity between orthopoxviruses and a broad spectrum of immune responses, in which antibodies target at least 24 structural and membrane proteins. Previous studies with Dryvax or other first-generation smallpox vaccines have shown complete protection against monkeypox in cynomolgus macaques, rhesus monkeys and chimpanzees.
There are currently two approved smallpox vaccines available in the United States, ACAM2000 and JYNNEOS. ACAM2000 is known to be only approved for smallpox, while JYNNEOS is approved for both monkeypox and smallpox. ACAM2000 is a second generation vaccine derived from a single clonal virus isolate from Dryvax. At the same time, JYNNEOS is a third-generation vaccine derived from a non-replicating modified vaccinia virus Ankara (MVA) strain, the genome of which has been 10% deleted. These vaccines can be used either before infection to prevent disease or after infection to reduce disease severity. In both cases, second- or third-generation vaccines have been found to produce significant results.
However, several side effects have been identified for both first- and second-generation vaccines. These include pain and swelling at the injection site, muscle pain, fatigue, lymphadenopathy, nausea and headache. Serious side effects included post-vaccination encephalopathy, vaccinal eczema, progressive vaccinia, vaccinia and death. It is reported that common side effects of JYNNEOS are fatigue, nausea, headache, chills and muscle pain. It was found that both ACAM2000 and JYNNEOS have similar immunogenicity, while side effects are said to be lower for the latter. Another third-generation vaccine, LC16m8, has been reported to be derived from the Lister strain used in the first-generation vaccines. It was licensed in Japan. However, it has not been submitted to the FDA for approval in the US. The immunogenicity and side effects of the LC16m8 have been observed to be similar to those of the Lister parental strains.
Studies in non-human primates
Non-human primates are better models of human disease. Studies of all three generations of vaccines in non-human primates showed that first-generation vaccines offered the strongest protection. Most of the animals receiving these vaccines showed no signs of clinical disease, limited skin rash was observed and transient low-level viraemia was noted. Protection from second-generation vaccines has been found to be similar to that from first-generation vaccines.
Although third-generation vaccines were found to offer strong protection, breakthrough infections became more common. In addition, it was reported that the rashes were more severe compared to the first or second generation vaccines. Antibody titers were also slightly higher with the first or second generation vaccines than with the third generation vaccines.
human studies
Several previous studies have reported that prior smallpox vaccination reduces the rate of monkeypox attacks and causes milder symptoms in vaccinated individuals compared to unvaccinated individuals. However, a crucial factor in the current outbreak is sexual activity. This could indicate a lowered threshold for contagion through sexual activity or a new mode of transmission. Unfortunately, none of the previous studies evaluated such scenarios. Therefore, more studies are needed to understand monkeypox transmission and the effectiveness of vaccines against the current outbreak.
hypotheses and concerns
The current outbreak of monkeypox has resulted in more than 61,000 confirmed cases in 104 non-endemic countries. Most of these cases have been reported in adult males, with a mean age of 38 years. The changing epidemiology of the current outbreak may be due to human behavior, the ability to leave high-risk areas and reach international destinations within the country before symptoms appear, and the lack of prior smallpox vaccination. A striking feature of the current infection is its rapid transmission, possibly due to viral mutations. Two circulating virus strains have been identified in the US that carry multiple mutations suggestive of longer-term subclinical transmission. In addition, it has been reported that the causative virus of the current outbreak belongs to the West African group previously observed to cause a milder disease with fewer deaths.
However, the establishment of an animal reservoir outside of West or Central Africa by monkeypox virus is currently a major problem. This reservoir could appear in the prairie dog, rodent, or exotic small animal trade. This could mean that eradication of the disease would not be possible and the world population would remain at risk.
Conclusion
Human monkeypox disease poses a significant risk to the human population. Risk groups include infants, young children, immunocompromised individuals, and pregnant women. Smallpox and monkeypox vaccines and two antivirals to combat the disease are available in the United States. However, deciding when to use them is crucial. The risk, benefit, availability and utility of the vaccines will influence such decisions.
In addition, evolution of the monkeypox genome may increase the risk of transmission, lead to higher virulence and lower antiviral efficacy of existing vaccines and drugs. With ongoing challenges related to COVID-19, fragile economies, climate change, supply chain issues and threats of war, such risks must be prepared. Healthcare providers, public health officials and the general public need to be educated about the threat of emerging diseases. For such diseases, efficient tracking, diagnosis and treatments need to be developed to ensure global security.
