Vaccine and Monkeypox | Encyclopedia MDPI

The monkeypox virus (MPV) is a double-stranded DNA virus belonging to the Poxviridae family, Chordopoxvirinae subfamily, and Orthopoxvirus genus. It was called monkeypox because it was first discovered in monkeys, in a Danish laboratory, in 1958.

monkeypox
vaccine
outbreak

1. Monkeypox: The Past and Now

The monkeypox virus (MPV) is a double-stranded DNA virus belonging to the Poxviridae family, Chordopoxvirinae subfamily, and Orthopoxvirus genus [1]. It was called monkeypox because it was first discovered in monkeys, in a Danish laboratory, in 1958 [2]. However, the actual reservoir for MPV is still unknown [3]. On the other hand, the first reported case in humans was in an infant in the Democratic Republic of the Congo (DRC) in 1970 [4]. Then, it spread among other African countries, mainly Central and West Africa. Finally, in 2003, it started to spread outside Africa [5], reaching the United States by importing animals from Ghana [6]. Genetically, MPV has two clades: the West African and the Central African (Congo Basin) clade [7].

A systematic review showed that the number of monkeypox cases was highest in DRC, particularly in Central Africa, with 38, 520, and 85 confirmed cases reported during 1970–1979, 1990–1999, and 2010–2019, respectively. Outside Africa, mainly in the United States, MPV was detected in 47 cases from 2000–2009 [6]. That being said, MPV started re-emerging in 2022, affecting numerous patients with no connection worldwide. As of 3 July 2022, MPV was confirmed in 5783 cases in more than 52 nonendemic countries, with the highest numbers in the United Kingdom, Germany, Spain, France, the USA, and Portugal, in decreasing order [8].

This virus infects humans, causing monkeypox, which is quite similar to the disease caused by the smallpox virus. MPX has similar presentation and severity to smallpox but is associated with lower mortality (3–6% in the recent multicountry outbreak) and less human-to-human transmission [9,10]. Moreover, smallpox vaccines have been shown to provide cross-protection to MPV in 85% of cases [11]. As a result, the incidence rate of the MPV is highest among unvaccinated patients [6].

Current vaccines, although they provide cross-protection against monkeypox, are not specific for the causative virus and their efficacy in the light of the recent multicountry outbreak is still to be confirmed. In addition, as a consequence of the eradication and cessation of smallpox vaccination for four decades, MPV found an opportunity to re-emerge, but with different characteristics.

2. Prevention and Prophylaxis

Our immune system includes innate and adaptive components; innate immunity is the first defence line against infections, represented by physical, chemical, and microbiological barriers. Meanwhile, adaptive immunity comes after a previous infection to act specifically toward the previous immunogenic antigen [12]. In this regard, vaccines protect against such antigens without prior exposure, especially in prevalent infectious diseases.

One of the recent examples is the COVID-19 pandemic, which did not only affect the preparedness of the global healthcare system, but also affected it at the individual level, limiting the daily life activities of many people. The burden of COVID-19 pandemic was not reduced, in terms of associated morbidity and mortality, until effective vaccines were developed and disseminated. The herd immunity threshold level is calculated mathematically for each population; if this level is achieved, it will lead to herd immunity or population immunity, which protects unvaccinated individuals of the people indirectly when a certain percentage of the same population has been vaccinated and infected [13].

Herd immunity is a remarkable measure of vaccine efficacy. It helps to control and contain infectious diseases. However, the unknown mechanism of herd immunity led the researchers to understand its dynamics better to use it wisely in this era of newly emerging and re-emerging diseases [14], especially if the vaccines cannot cover the whole population for many reasons, including economic, religious, or medical reasons.

3. What Are the Different Types of Vaccines?

Live (-attenuated) vaccines are produced from weakened live viruses; they replicate in the host and create a milder form of the natural infection resulting in an immune response identical to natural infection. They do, however, have a slight risk of fatal infections when they replicate uncontrollably and, therefore, cannot be given to immunocompromised patients. There is also a risk of vertical and horizontal spread caused by contact with contaminated material [15]. The differences between live-attenuated and killed vaccines are highlighted in Table 1.

Table 1. The differences between live-attenuated and killed vaccines.

	Live	Killed
Virus	Weakened Live virus	Entire virus is killed
Replication	Can replicate and mimic natural infection	Do not replicate
Immunity	Greater and longer duration	Lower and Shorter duration
Immune response	Cell-mediated	Humoral
Adjuvant	Not needed	Needed
Ig produced	IgA and IgG	IgG
Virulence	May reverse	No virulence
Booster	Not required	Required
Spread of strain	Vertical and horizontal spread	Not possible

Inactivated virus vaccines consist of whole viruses that have been treated with chemicals or heat. Chemicals, such as phenol and formaldehyde, and heat cause the denaturation of the surface proteins, inactivating them and making them noninfective. The treatment of the whole virus leaves some unchanged epitopes, which maintain some of their integrity and evoke an adaptive immune response by initiating antibody formation [16]. When injected, phagocytic immature dendritic cells divide the virus into smaller antigenic fragments, which are presented as antigenic fragments on the surface of MHC cells leading to the activation of B cells and T helper cells. Inactivated vaccines are safe with no adverse reactions. They are also noninfectious, heat-stable, and nontransmissible of the disease, as they cannot replicate. However, they are insufficient as a single dose and they usually do not provide immunity that is as strong as live vaccines; therefore, booster doses may be needed periodically to produce a sufficient immune response [17].

There are two types of mRNA vaccines: self-amplifying and nonreplicating. Self-amplifying vaccines contain codes for both the target antigen and the replicase complex, enabling the vaccine’s amplification. Nonreplicating RNA have codes for the target antigen alone and untranslated regions. Once inside the cell, the mRNA replicates to form a protein triggering an immune reaction and enabling the stimulation of both the innate and adaptive immune systems [18]. mRNA vaccines have many advantages; they can effectively activate both humoral and cell-mediated immunity, producing durable immune memory. Production of these vaccines is fast and inexpensive; thus, a large number can be made in a short time. In addition, they are stable, carry no risk of infection, do not integrate with the host genome, and are naturally degraded [19]. Noteworthily, a concern associated with this type of vaccine is the unknown risk for long-term adverse events [20].

4. Available Vaccines for Monkeypox Virus

Preventing the transmission and infection of MPV is associated with different challenges. The primary strategy of prevention would be vaccination. However, no specific vaccines have been developed for MPV. On the other hand, many previous studies conducted in the aftermath of smallpox infections demonstrated that smallpox vaccines could be effectively used to protect against the MPV [21]. For instance, older evidence indicates that smallpox vaccines might induce a cross-reaction with the MPV and can be efficacious as 85% in preventing the infection [22]. However, it should be noted that not all of these vaccines are primarily used because of their associated side effects and complications [23], which will be discussed in the following section.

Evidence indicates that remarkable advances have been introduced to vaccine technology after smallpox to enhance the safety and efficacy of these vaccines. Three generations of smallpox vaccines were developed accordingly with enhanced features [24]. For instance, first-generation smallpox vaccines were usually propagated through calfskin and collected at calf lymph. However, using these vaccines from the Smallpox Eradication Program (SEP) kept in national and WHO reserves is not currently recommended for MPV interventions. On the other hand, second-generation smallpox vaccines are produced with modern, sound manufacturing practices and propagated in tissue cell cultures. Accordingly, these vaccines have a reduced risk of contamination by surrounding factors.

Moreover, it has been shown that both of these generations are usually associated with an increased risk of developing adverse events as they have a replication-competent vaccinia virus [25,26]. Third-generation smallpox vaccines are manufactured similarly to second-generation ones. However, they have enhanced safety profiles because they contain attenuated vaccinia viruses rather than replication-competent vaccinia ones [5,27,28]. Table 2 summarises the structure and efficacy of currently available vaccines to help prevent MPV infection.

Table 2. Structures, generations, and effectiveness of reported smallpox vaccines for preventing monkeypox infections.

Vaccine	Generation	Effective for	Use for Monkeypox	Structure	Injection Materials	Presentations
LC16	3rd generation	Infants, children, and adults (all ages)	No	Minimally replicating vaccinia virus	Bifurcated needle	Freeze-dried Multidose vials
ACAM2000	2nd generation	Adults (18–64)	USA: postexposure prophylaxis	Propagated in tissue cell culture and produced under good manufacturing practices (live, replication-competent virus)	Bifurcated needle	Freeze-dried Multidose vials
JYNNEOSTM/MVA-BN	3rd generation	General adult population	Yes (USA, UK, Canada)	Nonreplicating vaccinia virus	Needle and syringe (subcutaneous administration)	Liquid frozen or lyophilised (freeze-dried) Single-dose vials (Multidose vials possible)
Vaccinia (Dryvax, Lister, Copenhagen)	1st generation	-	No	Several different strains of vaccinia virus propagated in calf lymph (live, replication-competent virus)	Bifurcated needle	Liquid frozen or lyophilised vials or ampoules

The Food and Drug Administration approved the second-generation smallpox vaccine ACAM2000 to be used in emergencies and outbreaks of smallpox for postexposure prophylaxis. Accordingly, it has been purchased for the Strategic National Stockpile (SNS) and was used for different population groups [1]. Furthermore, in 2019, MVA-BN or JYNNEOS^TM was approved in the United States and Canada after various animal studies, and clinical trials showed the high efficacy and safety of this vaccine, which can also be used in different population groups for the prevention of MPV infection [2,29,30,31,32,33,34,35,36]. Furthermore, JYNNEOS^TM was approved based on the data suggesting its noninferior immunogenicity to other smallpox vaccines, its efficacy in animals, and its safety profile in humans [27,37,38,39,40,41]. Moreover, LC16 has been approved in the United States by the emergency investigational new drug program of the US Food and Drug Administration and in Japan, secondary to the reported protective effects in animal models and immunogenicity in human studies [41,42,43]. Although LC16 is the only approved smallpox vaccine for use in children, there are no data on its efficacy in preventing MPV infection.

It should be noted that these vaccines are usually efficacious in preventing MPV infection when used as pre-exposure approaches. Nevertheless, experts demonstrated that postexposure vaccination could also intervene against the development of severe diseases or reduce the severity of the conditions of infected MPV patients [44]. In this context, it can be suggested that it is better to be vaccinated sooner after exposure. Evidence from the Centers for Disease Control and Prevention (CDC) recommends that vaccinating exposed individuals should be conducted within four days of exposure to prevent the onset of the disease [45]. Therefore, the beginning of the illness may be inevitable in individuals that did not receive the vaccination within this period. However, vaccination within the first two weeks might intervene against developing the severe disease [46].

There is also evidence that the protective efficacy of smallpox vaccines usually fades over time. However, it has been shown that postvaccination protection might last for up to 20 years. Besides, although the protective efficacy of the smallpox vaccine fades with time, vaccinated individuals will still have lifelong protection against developing a severe disease secondary to the presence of memory B and T cells [41,47]. Therefore, immunity against the MPV should be expected in previously vaccinated individuals against smallpox [48]. The CDC also recommends that vaccination be given to individuals exposed to the MPV and not vaccinated within the last three years [45]. In this context, it has been demonstrated that receiving the smallpox vaccine as soon as possible would be more effective in preventing MPV infection [49].

This entry is adapted from the peer-reviewed paper 10.3390/vaccines10091419

© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.