In May 2022—when CAS Insights originally wrote about mpox—there had been under 400 confirmed or suspected cases of the disease. As of August 2024, more than 99,518 cases have been identified in 122 countries worldwide making it the largest mpox outbreak in history. Reacting to this, the WHO Director-General declared mpox a public health emergency of international concern.  

Note: “Mpox” is the preferred term for “monkeypox,” which has been phased out by the WHO over the last year.

How is mpox transmitted?

Mpox virus is a double‐stranded DNA (dsDNA) virus with a genome size of around 190 kb. In contrast to SARS-CoV-2, the mpox virus is much larger in size, does not aerosolize, and travels only a few feet before dropping in the air. It enters the body through broken skin, the respiratory tract, or mucous membranes. The virus also does not linger in the air as the SARS-CoV-2 virus does. For human-to-human transmission through air, it takes prolonged face to face contact with an infected individual.  It can also be spread through direct contact with body fluids, lesions, or indirect exposure to lesion material such as clothes or bedding. Animal-to-human transmission can occur by bite or scratch, bush meat preparation, and direct or indirect contact with body fluids or lesions.  However, mpox vaccines are highly effective due to the virus’s slower mutation rate when compared to SARS-CoV-2.

The changing vaccination and prevention landscape

Prevention of mpox involves several strategies, including vaccination, public health measures, and education. Raising awareness about mpox, its transmission, and prevention methods is crucial for controlling outbreaks. Infected individuals should be isolated to prevent the spread of the virus to others.

Vaccination remains a cornerstone of mpox prevention. Historical data have shown that smallpox vaccination with vaccinia virus was approximately 85% effective against mpox. The vaccine can be administered before or after exposure to the virus to reduce the severity of the disease. Currently, there are three vaccines (JYNNEOS, ACAM2000, LC-16) approved to be used against mpox by different jurisdictions, but their availability varies in different geographical areas.  

JYNNEOS (MVA-BN) vaccine

The JYNNEOS vaccine, also known as Imvanex (in Europe) and Imvamune (in Canada), manufactured by Bavarian Nordic A/S, is a third-generation, non-replicating live virus vaccine based on the Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) strain that was initially developed to protect against smallpox. Given the genetic similarities between the smallpox and mpox viruses, Jynneos is also effective against mpox. A systematic review and meta-analysis reported vaccine effectiveness of 76% and 82% with 1 dose and 2 doses of MVA-BN respectively in humans. The Jynneos vaccine is approved by the U.S. FDA for the prevention of smallpox and mpox and is the country’s prime vaccine being used against mpox. It is recommended for individuals at high risk of exposure, such as healthcare workers, laboratory personnel, and those who have had close contact with confirmed cases. It is administrated by subcutaneous (< 18 years) or intradermal routes (for a high-risk population), four weeks apart. Recently, WHO announced the JYNNEOS vaccine as the first WHO prequalified vaccine against mpox. The WHO prequalification of the JYNNEOS vaccine will help accelerate ongoing procurement of the mpox vaccines by international agencies and national regulatory authorities, ultimately increasing access to quality-assured mpox vaccine products.

ACAM2000 vaccine

ACAM2000, manufactured by Emergent Biosolutions, is a second-generation smallpox vaccine that is U.S. FDA-approved against smallpox and available for mpox under the Expanded Access Investigational New Drug (EA-IND) protocol sponsored by the Centers for Disease Control and Prevention which requires informed consent along with additional IND requirements. Unlike Jynneos, ACAM2000 is a live, replicating vaccinia virus vaccine, which means it contains a virus that can still replicate within the body. As a result, it can cause more side effects and is not recommended for people with weakened immune systems, skin conditions like eczema, or pregnant women. It is given as a single dose through a method known as scarification, where a small drop of the vaccine is placed on the skin and pricked into the surface with a bifurcated needle. While ACAM2000 is effective at preventing mpox, it is generally reserved for individuals who cannot receive Jynneos or who require rapid immunity due to its potential side effects.

LC16m8

LC16m8 is a live attenuated, third-generation smallpox vaccine developed by The Chemo-Sero-Therapeutic Research Institute (also referred to as KAKETSUKEN), Kumamotoin, Japan. It is a derivative of the Lister strain of vaccinia by passaging multiple times, with selection for an attenuated phenotype. It is administered as a single dose as ACAM2000 using a bifurcated needle–scarification method. It has been shown to have a safer profile compared to traditional smallpox vaccines, with less risk of severe adverse effects. In August 2022, Japan extended the indication of this vaccine to include protection against mpox.  

Promising new vaccine candidates

Ongoing vaccine research is exploring new candidates and improving existing options to enhance global preparedness. Various DNA-based vaccines targeting mpox are in development. These vaccines involve inserting genes that encode mpox antigens into DNA plasmids, which then stimulate an immune response. DNA vaccines are attractive due to their stability, ease of production, and ability to target multiple viral strains. Inspired by the success of mRNA vaccines for COVID-19, research is underway to develop mRNA vaccines for mpox. Xidan Yang et al. developed two mpox mRNA vaccine candidates based on A29L, M1R, A35R, and B6R of mpox virus, designated as MPXfus (one component) and MPXmix (multi-component). Both elicit a high level of antigen-specific antibodies and robust cellular immune response in mice. A study reported mpox virus mRNA-lipid nanoparticle vaccine candidates evoke antibody responses. Another novel vaccine candidate, TNX-801 horsepox-based live virus vaccine, has been designed to protect against smallpox and mpox.

Challenges and future directions

Despite significant progress in understanding and controlling mpox, several challenges remain. Ensuring equitable access to vaccines, particularly in endemic regions, is a critical challenge. Many African countries, where mpox has been a persistent problem, have limited access to vaccines and antiviral treatments. Global efforts are needed to address these disparities and ensure that all populations are protected. Increasing public awareness about mpox, particularly in non-endemic regions, is essential for preventing future outbreaks. Public health campaigns should focus on educating communities about the risks of zoonotic diseases and promoting behaviors that reduce the risk of transmission.  

Continued research is needed to develop more effective vaccines, antiviral treatments, and diagnostic tools for mpox. This includes exploring the use of mRNA technology, which has shown promise in rapidly responding to emerging infectious diseases. Strengthening global surveillance and reporting systems is also crucial for early detection and response to mpox outbreaks. Improved surveillance can help identify new cases more quickly and track the spread of the virus, allowing for more effective containment measures.

Background information on mpox

Updated from previous CAS Insights article published in May 2022.

What is mpox?

Mpox virus is classified in the family Poxviridae with the genus Orthopoxvirus. The CAS Content Collection™ shows the phylogeny of the mpox virus. It is within the same family as a common childhood skin disease, Molluscum contagiosum, and the same genus as viruses like the vaccinia virus (cowpox virus) and variola virus (smallpox virus). It is not related to the commonly known chicken pox virus (Varicella). It was first discovered in 1958 in colonies of research monkeys that developed a pox-like disease, with the first human case reported in the Democratic Republic of the Congo (DRC) in 1970. Mpox is classified as a zoonotic disease with transmission being primarily from animal to human or vice versa. This current outbreak however has shifted to human-to-human transmission in non-endemic countries (Figure-2), baffling many and bringing this rare disease to the headlines.

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Virology and pathogenesis of mpox

The mpox virus is characterized by its brick-shaped or oval morphology with a diameter of ~200–250 nm.  Its genome consists of a linear, double-stranded DNA with a length of ~197 kb, encoding about 180 proteins.  Additionally, mpox virus possesses a dumbbell-shaped nucleocapsid enveloped by ovoid lipid-containing particles (Figure 2).  The mpox isolates are classified into three genetically distinct clades: (i) the clade I (formerly designated as clade 1), which is also known as “Central African” or “Congo Basin” clade, containing isolates from the Congo Basin with mortality rates of around 10.6%, (ii) the clade IIa (formerly designated as clade 2) also known as “West African” clade and contains isolates from the countries in western Africa with mortality rates of around 3.6%, and (iii) clade IIb (formerly designated as clade 3), which is descendant from clade IIa and includes the isolates of the 2022 mpox outbreak.  

Upon entering the body, the virus targets the epithelial cells of the skin, mucous membranes, and the respiratory tract. It replicates within these cells, causing cell death and leading to the characteristic skin lesions seen in mpox. The immune response to the virus includes both humoral and cellular immunity.

Updated 16 September 2024