Monkeypox pandemic containment: does the ACAM2000 vaccine play a role in the current outbreaks?

KEYWORDS:

• Mpox
• monkeypox
• ACAM
• vaccine
• safety

1. Introduction

Monkeypox (Mpox) is a zoonotic viral disease belonging to the Orthopoxviral genus of the Poxviridae family [1]. Mpox can spread from animals to humans and vice versa by direct contact with infectious rashes, crusts/fluids from saliva, or infected body fluids including sweat and respiratory secretions [2,3]. Several species of mammals are suspected to be natural reservoirs of Mpox. Since the 1980s the quantity and severity of human outbreaks have significantly increased.

The first presentation in humans was reported in 1970 in central Africa. Between 1991 and 1999 another human outbreak occurred in the Democratic Republic of Congo (DRC), and approximately 511 cases were reported [4]. Additionally, 3–6% of diagnosed cases died by 2022. In 2003, the first Mpox outbreak outside of Africa was reported in the Midwestern United States. Seventy-one people were infected with no deaths being reported [5]. In 2005, 49 cases were reported in Sudan, and a genetic analysis study revealed that the virus did not originate in Sudan but originated elsewhere, most probably from DRC [6]. Many more Mpox cases have been reported in Africa and in the DRC in particular, around 2000 cases per year were reported between 2011 and 2014 [4]. Between 1971 and 1978, 10 human-Mpox infections were reported in Nigeria. During September 2017,118 cases were confirmed followed by the first reported case in the United Kingdom reported In September 2018. The current outbreak started in May 2022 where cases were reported outside endemic areas in Europe, Oceania, Asia, and America. More than 16,000 people across more than 70 countries have been confirmed, the current death rate is 0.03% [7].

Although the disease is self-limited, it may cause complications especially in infants, children, and immunocompromised patients. The WHO declared that Mpox is a public health emergency, and a coordinated response is crucial to stop transmission and protect vulnerable groups. Self-protection is a must. In countries where animals and humans carry Mpox, healthy individuals should avoid close contact with infected people, wear face masks, and always seek medical advice if they note any new symptoms. There are currently two vaccines available in the United States for Mpox prevention [8,9]; JYNNEOS which is the most used and ACAM2000 [10].

2. What is ACAM2000 vaccine?

ACAM2000 is a live-attenuated, replication-competent vaccinia virus vaccine that was first produced in France and U.S.A. The ACAM2000 vaccine was approved by the US FDA as a 2^nd-generation vaccine to be used in times of emergency and outbreaks to combat smallpox as a post-exposure prophylactic agent. Despite the availability of other vaccines such as JYNNEOS and LC16, the ACAM200 vaccine was the first to be licensed for use against Mpox in 2015. It was the only available vaccine for Mpox in the U.S.A from 2015 to 2019 [10].

The vaccine is given as a single dose by applying several pricks to the skin with the help of a bifurcated needle. This technique allows the inoculation of multiple portions of the vaccine into the skin surface. The occurrence of a skin reaction, termed ‘take,’ is indicative of vaccine efficacy. This ‘take’ involves the formation of a pustule in the skin at the site of vaccination. During this period, the individual can be infectious to others and infection can spread from the inoculation site to other body parts. Immunization is typically affirmed 28 days after vaccination [11]. ACAM2000 has been approved for usage in individuals between 18–64 years of age. Primary vaccination is contraindicated in cases of severe immune deficiency such as people living with HIV, people with a history of atopic dermatitis, pregnant (as fetal vaccinia is feared), breastfeeding women, in the presence of active exfoliative skin conditions, patients with underlying cardiac diseases or major cardiac risk factors, and those below the age of one [12].

3. Effectiveness in limiting disease progression and/or transmission

Given the similarities between smallpox and Mpox, smallpox vaccines including ACAM2000 are proposed to provide fair protection against Mpox [10]. It can be given before or after viral exposure. In a study conducted in the Democratic Republic of Congo in 1980 close contacts of unvaccinated individuals showed a 9.28% Mpox virus attack rate compared to 1.31% for close contacts of vaccinated individuals. This data suggested that Vaccinia virus-based vaccines yielded approximately 85% protection against Mpox, the study however didn’t specify the vaccine used in enrolled participants [13]. A study published in 2010 conducted on Smallpox patients stated that in phase I of clinical trials, ACAM2000 produced an effective response in unvaccinated participants, 96.7% had positive antibodies and a successful skin reaction ‘take.’ Phases II and III were conducted on both vaccinia-naïve and previously vaccinated individuals. During phase II ACAM2000 produced a 100% take rate and 94% seroconversion rate in vaccinia-naïve participants compared to an 88% take rate in previously vaccinated individuals. Phase III demonstrated a 96% take rate in vaccinia-naïve compared to 84% in previously vaccinated individuals. These results indicate that ACAM2000 is more effective in unvaccinated individuals [11]. ACAM2000 resulted in a four-fold increase in neutralizing antibodies in most participants, this indicates that it should be protected in the event of exposure. It proved effective in producing a cell-mediated immune response in almost all participants and met two of the four efficacy endpoint criteria established for Phase III [11,14]. There are no recent studies conducted to assess the exact effectiveness of ACAM2000 against Mpox virus and very little information regarding its efficacy and safety amongst pregnant women and no information regarding children [14]. Further studies are needed to provide more insight into the exact efficacy against Mpox as there is no available data to date regarding its efficacy against the Mpox virus, and no studies have been conducted to this day.

4. Safety concerns and adverse events

ACAM2000 side effects include constitutional symptoms such as fever, malaise, headache, myalgia, and lymphadenitis. Severe side effects are rare but may occur such as skin infection, progressive vaccinia, generalized vaccinia, erythema multiform, myocarditis, pericarditis, post-vaccination encephalitis, encephalopathy and encephalomyelitis have been reported [15] [Table 1]. One study showed that 1 in 175 vaccinated people experience myocarditis or pericarditis [16], approximately 5.73 myocarditis cases, and 0.54 myopericarditis cases per 1000 individuals [14]. Among 730,580 members of the Department of Defense vaccinated with ACAM2000 there were 3 cases of post-vaccination encephalitis and 43 reported mild generalized vaccinia [11]. Another study conducted in 2021 on 897,227 US military service members reported 384 cardiovascular side effects including 144 cases of myocarditis, 106 pericardial disease, 82 pericarditis, and 33 acute myocardial infarctions, event onset was within 30 days of vaccination. Non-cardiovascular side effects included 336 cases of chest pain, 137 dyspnea, 77 syncope, and 28 cases of palpitations [17]. Another registry-based study analyzed 1149 reports of ACAM2000 vaccines, of which 14.7% had serious adverse events requiring hospitalization (defined as life-threatening illnesses leading to permanent disabilities or death) [18].

Table 1. Reported ACAM2000 vaccine adverse events in the literature.

Complication	Frequency (%)	Reference
Myocarditis or Pericarditis	0.581	[16]
Myocarditis	0.573	[14]
Myopericarditis	0.054	[14]
Encephalitis	0.00041	[11]
Mild Generalized Vaccinia	0.00589	[11]
Myocarditis	0.016	[17]
Pericardial disease	0.012	[17]
Pericarditis	0.0091	[17]
Acute Myocardial Infarction	0.0037	[17]
Chest Pain	0.037	[17]
Dyspnea	0.015	[17]
Syncope	0.0086	[17]
Palpitations	0.0031	[17]

Accidental infections have been reported 5–12 days post-vaccination due to improper care for vaccination sites, and inoculation may occur through eyelids, conjunctiva, mouth, lips, genitalia, and anus [15]. The vaccine is not recommended for those living with or in close contact with pregnant women. It is unknown if the vaccine virus or antibodies are secreted in breastmilk, however, live vaccinia virus may be transmitted to infants through direct contact or inoculation [15]. The vaccine is believed to have little effect on pregnancy, but no studies have been conducted to measure if it increases the chance of miscarriage, birth defects, or other pregnancy-related problems [15]. Other side effects may be expected to arise as there is no available data on the side effects associated with ACAM2000 use in cases of Mpox.

5. Ongoing trials and future directions

There is currently no definitive data on the use of ACAM2000 in the prevention and/or treatment of Mpox specifically. Despite the availability of several trials on the JYNNEOS vaccine against Mpox, there are no ongoing trials registered on clinicaltrials.gov regarding the efficacy/safety of the ACAM2000 vaccine in light of the current Mpox pandemic. This highlights the great need to conduct further research in this regard to drive evidence-based recommendations for the containment of the current pandemic before this becomes a global necessity.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

Conceptualization and design of this Editorial and interpreting the relevant literature [A.A., B.E.K., F.L., and M.M.]; writing the Editorial article or revision for intellectual content [B.E.K., M.M., F.L., and A.A.].

Additional information

Funding

This paper was not funded.