Monkeypox and Immunosuppressed Neurological Patients: What can we Advise Vaccination in Multiple Sclerosis and Neuromyelitis Optica Patients?

Monkeypox is a zoonotic viral disease that was identified in 1958 in research monkeys that came from Singapore. It is an orthopoxvirus that belongs to the Poxviridae family [1]. This viral infection was restricted to Africa but in the last year the cases started raising not only in Africa but in the rest of the world [1,2]. This is why it became a disease of interest; it is important to acknowledge its epidemiological behavior, risks and vaccines, especially in a world that was recently struck by COVID-19, challenging physicians in the way of treating and vaccinating their immunosuppressed patients.

In this issue of the journal, Jesmin S, et al. [2] discuss the epidemiological changes that monkeypox has experienced during the last decades especially in its transmission and geographical spread. Special interest are the countries with new cases that are not endemic or do not have an epidemiological linkage to the disease, for example United Kingdom, Spain or Portugal. The increase in the numbers is important because it is likely that one or more of our neurological and immunosuppressed patients will face the disease or the decision to get vaccinated or not.

Is there an effective vaccine to prevent the spread or that will reduce the impact of the disease? Can it be used in immunosuppressed patients? General population and patients vaccinated against smallpox in the past may have protection against monkeypox, being less likely to contract the disease or to have complications [1], but smallpox vaccines for the general population are no longer available, so people younger than 40 years old are unlikely to be vaccinated as part general plan of immunization in their countries [3]. The developed, approved and today available vaccines for smallpox are also approved for monkeypox due to the 85% effectiveness provided by cross-immunity [4] but precaution should be taken for those with severe immunodeficiency depending on the type of vaccine acquired by the local authorities [5]. Different countries are having a strict policy to define high risk groups to vaccinate in terms of exposure: pre-exposure based on occupational probability (healthcare professionals, laboratory personnel and outbreak response team members) plus homosexual, bisexual, and other men who have sex with men and post-exposure prophylaxis for contacts of confirmed cases [4].

There are 2 types of vaccines: second and third generation. Second generation vaccines called replication competent vaccinia virus vaccines due to their replication capacity in mammalian cells (examples ACAM2000 and APSV approved for > 18 years old) that are associated with complications or adverse events that can be severe amongst immunocompromised individuals with no safety study in HIV population or pregnant population [5,6]. For example, after vaccination with these vaccines, we can have common local side effects such as pain, erythema or induration and common systemic side effects such as fever, chills, fatigue, myalgia, headache, nausea that are generally mild and transient [6]. The important fact comes with the rare but severe adverse events, especially in immunocompromised population such as post-vaccination encephalitis and myopericarditis [6], blindness, eczema vaccinatum, encephalomyelitis, encephalopathy, erythema multiforme major, fetal death, generalized vaccinia, ocular complications, progressive vaccinia, and severe vaccinal skin infections [5]. This type of vaccine is not recommended in pregnant women or any group of immunosuppressed patients, especially those with inflammatory /autoimmune diseases of the central nervous system where we can have an outbreak of the disease [7].

Third generation vaccines, for example MVA‐BN/JYNNEOS/Imvamune, are highly attenuated live vaccinia virus vaccine. It is a replication deficient vaccinia vaccine with a good safety profile compared with replication competent smallpox vaccines, so they can be given to healthy individuals and persons with immune deficiencies, HIV infections, atopic dermatitis, or allergic rhinitis [5]. They produce humoral and cellular responses to orthopoxviruses [5], being a good ally when a part of the immunity is shut down due to immunosuppressant drugs or monoclonal antibody therapies. Regarding the adverse events, the most frequent one observed for MVA‐BN is mild to moderate pain at the site of injection [5]. JYNNEOS has minimal adverse events and it authorized to be used in immunosuppressed patients [8]. Special note is required to the myopericarditis following receipt of ACAM2000, because its mechanism is thought to be an immune-mediated phenomenon and it is not known whether the antigen or antigens that precipitate autoantibodies are present in JYNNEOS [8].

Multiple sclerosis and neuromyelitis optica spectrum disorder are autoimmune diseases that causes disability every time there is a relapse of the disease. Both are treated with highly effective immunosuppressive treatments that include monoclonal antibodies (anti CD52 – alemtuzumab, anti CD20 – rituximab, ocrelizumab, ofatumumab, anti IL6R – satralizumab, tocilizumab, anti α4β1 integrin – natalizumab, antiC5 – eculizumab, antiCD19-inebilizumab) or immunosuppressant drugs (cladribine, fingolimod, ozaminod, ponesimod, siponimod, azathioprine, mycophenolate mofetil). Eventually, these patients will need vaccination as a prophylaxis if they have close contact with a monkeypox patient or get infected with the disease in order to reduce the risk of serious complications. As general knowledge, immunosuppressant drugs reduce the humoral response to vaccines [9]. A warning was set for patients with relapsing diseases, as the listed before, because previous publications in multiple sclerosis and vaccination against yellow fever with live attenuated replicant vaccines showed that vaccination exacerbated the activity of multiple sclerosis in terms of relapse rate, new T2 lesions and/or T1 gadolinium enhancing lesions in the brain images [7].

In conclusion, before recommending or not to vaccinate this particular group of immunosuppressed patients, who can have severe complications with a live attenuated vaccine but also an exacerbation of their autoimmune neurological disease, it is important to be well informed of the type of vaccine that the local authorities are obtaining. If it is a second generation live attenuated vaccine, these patients should not receive the vaccine. If it is a third generation live attenuated vaccine with no replication capacity and proven to be safe in immunosuppressed patients, then vaccination should be advised, always taking into consideration that the underlying disease should not be active at the moment of the inoculation.

L.G. has received personal compensation for consulting, serving on a scientific advisory board, lecturing as well as professional travel/accommodation stipends among other activities from Biogen Idec, Sanofi Genzyme, Merck Serono, Novartis, Teva, and Roche.

The author received no financial support for the research, authorship, and/or publication of this article.

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