Researchers investigate prevention and therapy against monkeypox infection
In a recent study published in the journal Drugs, researchers reviewed preventive and therapeutic measures against monkeypox.
The human monkeypox virus is a double-stranded (ds) deoxyribonucleic acid (DNA) virus belonging to the genus orthopoxviruses. The monkeypox infection has manifestations similar to that observed in smallpox. According to the Center for Disease Control and Prevention (CDC), there are no treatments specifically for monkeypox infections currently.
Prevention of monkeypox infection
Various studies have shown that previous vaccination against smallpox may induce a protective impact against the monkeypox virus and also treat the clinical symptoms associated with monkeypox. To date, there are a total of three smallpox vaccines including the approved JYNNEOSTM and ACAM2000 and the investigational new drug (IND) Aventis Pasteur smallpox vaccine (APSV).
JYNNEOSTM, developed from the modified vaccinia Ankara-Bavarian Nordic (MVA-BN strain), is a live viral vaccine that is an attenuated and non-replicating orthopoxvirus. This vaccine is employed as a preventive treatment against smallpox and monkeypox among adults aged 18 years and above who are deemed to be at risk for monkeypox and smallpox infections. Furthermore, previous data has revealed that smallpox immunization with the vaccinia virus was almost 85% effective against the monkeypox virus.
ACAM2000 comprises a live vaccinia virus and is used for vaccination against smallpox for persons who are at high risk of contracting the smallpox infection. The CDC has an emergency access IND protocol that allows the usage of ACAM2000 against non-variola orthopoxvirus infections such as monkeypox during infection outbreaks.
Aventis Pasteur smallpox vaccine (APSV) comprises a vaccinia vaccine that was replication-competent that could be used under an emergency use authorization (EUA) or IND in order to prevent a smallpox infection when other licensed vaccines are either contraindicated or unavailable. However, the effectiveness of APSV against monkeypox is not known.
The Advisory Committee and Immunization Practices (ACIP) has recommended vaccination against orthopoxviruses for selected individuals who are at risk for occupational exposure to the virus. Clinical laboratory personnel who perform diagnostic testing for orthopoxviruses, research laboratory personnel, and designated response team members who are at risk of being occupationally exposed to the virus are advised to be vaccinated against orthopoxviruses.
Monkeypox transmission requires close interaction for longer durations with a symptomatic person. Brief interactions, as well as interactions wherein appropriate protective personal equipment (PPE) were used, are not at high risk and do not require post-exposure prophylaxis (PEP).
On the other hand, incidences of high-degree of exposure to a symptomatic person are advised to be surveilled and receive a PEP vaccination. An intermediate degree of exposure warrants monitoring and an informed clinical decision to be taken on an individual basis to assess whether the benefits associated with PEP outweigh the corresponding risks. Additionally, low or uncertain exposures are advised to be monitored but have no recommendations regarding PEP.
Treatment of monkeypox
While most monkeypox patients recover without needing any medical attention, patients exhibiting gastrointestinal symptoms need oral or intravenous rehydration to curb any loss of gastrointestinal fluid.
Various antiviral drugs could also be effective in monkeypox treatment, as these medications were approved to manage diseases like smallpox.
Tecovirimat is the first approved antiviral that was used to treat smallpox in adults as well as pediatric patients and is deemed the treatment of choice. Patients exhibiting severe disease were treated with a dual therapy comprising tecovirimat and brincidofovir. Tecovirimat functions by the inhibition of the viral envelope protein which is responsible for blocking the final steps involved in viral maturation and the subsequent release from the infected cell, resulting in the inhibition of viral spread within the infected host.
Brincidofovir and Cidofovir
Brincidofovir is an antiviral that is used for smallpox treatment since June 2021 in the US. The orally administered brincidofovir is an analog of the antiviral cidofovir which is administered intravenously. Brincidofovir is found to have a better safety profile with lesser renal toxicity as compared to that observed in cidofovir. Both these antivirals function by viral DNA polymerase inhibition. Moreover, various studies have shown the effectiveness of brincidofovir against orthopoxvirus infections; however, there is limited research regarding brincidofovir treatment against monkeypox.
Vaccinia immune globulin (VIG)
VIG, a hyperimmune globulin, is authorized by the Food and Drug Administration (FDA) as a treatment approach against certain complications related to vaccinia vaccination. These complications include progressive vaccinia, eczema vaccinatum, vaccinia infections among persons suffering from skin-related conditions, severe generalized vaccinia, and aberrant infections elicited by the vaccinia virus. While the VIG could be a potential treatment approach, there is limited data regarding the efficacy of VIG against smallpox as well as monkeypox.
The study findings showed that while several monkeypox-infected individuals exhibit mild and self-limiting symptoms even without any medical interference, the prognosis of the infection may depend on various factors including initial health status, previous vaccination status, and concurrent comorbidities. Hence, the researchers believe that the development of personalized treatments according to the individual risk of experiencing severe infection symptoms is the most reasonable approach.