An overview on mRNA-based vaccines to prevent monkeypox infection.

The human monkeypox virus (Mpox) is classified as a member of the Poxviridae family and belongs to the Orthopoxvirus genus. Mpox possesses double-stranded DNA, and there are two known genetic clades: those originating in West Africa and the Congo Basin, commonly known as Central African clades. Mpox may be treated with either the vaccinia vaccination or the therapeutics. Modifying the smallpox vaccine for treating and preventing Mpox has shown to be beneficial because of the strong link between smallpox and Mpox viruses and their categorization in the same family. Cross-protection against Mpox is effective with two Food and Drug Administration (FDA)-approved smallpox vaccines (ACAM2000 and JYNNEOSTM). However, ACAM2000 has the potential for significant adverse effects, such as cardiac issues, whereas JYNNEOS has a lower risk profile. Moreover, Mpox has managed to resurface, although with modified characteristics, due to the discontinuation and cessation of the smallpox vaccine for 40 years. The safety and efficacy of the two leading mRNA vaccines against SARS-CoV-2 and its many variants have been shown in clinical trials and subsequent data analysis. This first mRNA treatment model involves injecting patients with messenger RNA to produce target proteins and elicit an immunological response. High potency, the possibility of safe administration, low-cost manufacture, and quick development is just a few of the benefits of RNA-based vaccines that pave the way for a viable alternative to conventional vaccines. When protecting against Mpox infection, mRNA vaccines are pretty efficient and may one day replace the present whole-virus vaccines. Therefore, the purpose of this article is to provide a synopsis of the ongoing research, development, and testing of an mRNA vaccine against Mpox.

A multivalent mRNA monkeypox virus vaccine (BNT166) protects mice and macaques from orthopoxvirus disease.

In response to the 2022 outbreak of mpox driven by unprecedented human-to-human monkeypox virus (MPXV) transmission, we designed BNT166, aiming to create a highly immunogenic, safe, accessible, and scalable next-generation vaccine against MPXV and related orthopoxviruses. To address the multiple viral forms and increase the breadth of immune response, two candidate multivalent mRNA vaccines were evaluated pre-clinically: a quadrivalent vaccine (BNT166a; encoding the MPXV antigens A35, B6, M1, H3) and a trivalent vaccine (BNT166c; without H3). Both candidates induced robust T cell responses and IgG antibodies in mice, including neutralizing antibodies to both MPXV and vaccinia virus. In challenge studies, BNT166a and BNT166c provided complete protection from vaccinia, clade I, and clade IIb MPXV. Furthermore, immunization with BNT166a was 100% effective at preventing death and at suppressing lesions in a lethal clade I MPXV challenge in cynomolgus macaques. These findings support the clinical evaluation of BNT166, now underway (NCT05988203).

Characterizing the acute antibody response of monkeypox and MVA-BN vaccine following an Australian outbreak.

In response to the emergence of the monkeypox virus (MPXV) in Australia in May 2022, we developed and evaluated indirect immunofluorescence assays (IFA) for MPXV and Vaccinia virus (VACV) IgG and IgM antibodies using serum samples from patients with nucleic acid amplification test (NAAT)-confirmed mpox and uninfected unvaccinated controls. Additionally, 47 healthcare workers receiving two doses of the third-generation smallpox vaccine Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) undertook serial serum collection to describe the serological response to vaccination. MPXV antibodies were detected in 16/18 individuals with NAAT-confirmed mpox (sensitivity 0.89, specificity 1.00), and VACV antibodies were detected in 28/29 individuals who received two doses of MVA-BN vaccine (sensitivity 0.97, specificity 1.00). Detectable antibody in subjects historically vaccinated with early-generation vaccines against smallpox was found in 7/7 subjects, at a median of 48 years following vaccination. MPXV NAAT-positive patients with serum samples collected within the first 14 days after rash onset had detectable IgG and IgM in 9/12 and 5/12 of patients, respectively, with maintenance of IgG and disappearance of IgM titers after 60 days. While specificity was high when testing unvaccinated and uninfected subjects, significant cross-reactivity between MPXV and VACV antibodies was observed.

Monkeypox: Can we count on the current smallpox immunization?

Two vaccines ACAM 2000 and JYNNEOS have obtained approval from the Food and Drug Administration as preventive measures against monkeypox, contributing significantly to the management of the monkeypox epidemic. Nonetheless, research has demonstrated that smallpox vaccination offers approximately 88.8% protection against monkeypox, while immunization with these vaccines generates relatively low levels of neutralizing antibodies. In this work, we performed a comprehensive comparison of antigens between the 2022-2023 monkeypox strains and the smallpox vaccine strains. Our analysis has revealed considerable amino acid changes in all 27 antigens, including core and envelope proteins. Amino acid substitutions within B cell epitopes were observed in 26 of these antigens, with at least half of the antigen substitutions occurring within B cell epitopes in 20 out of the 26 antigens analyzed. These findings may raise potential concerns regarding the efficacy of these vaccines.

Simulating the impact of optimized prevention and control measures on the transmission of monkeypox in the United States: A model-based study.

This study aimed to develop a modified susceptible-exposed-infected-recovered (SEIR) model to evaluate monkeypox epidemics in the United States and explore more optimized prevention and control measures. To further assess the impact of public health measures on the transmission of monkeypox, different intervention scenarios were developed based on the classic SEIR model, considering reducing contact, enhancing vaccination, diagnosis delay, and environmental transmission risk, respectively. We evaluated the impact of different measures by simulating their spread in different scenarios. During the simulation period, 8709 people were infected with monkeypox. The simulation analysis showed that: (1) the most effective measures to control monkeypox transmission during the early stage of the epidemic were reducing contact and enhancing vaccination, with cumulative infections at 51.20% and 41.90% of baseline levels, respectively; (2) shortening diagnosis time would delay the peak time of the epidemic by 96 days; and (3) the risk of environmental transmission of monkeypox virus was relatively low. This study indirectly proved the effectiveness of the prevention and control measures, such as reducing contact, enhancing vaccination, shortening diagnosis time, and low risk of environmental transmission, which also provided an important reference and containment experience for nonepidemic countries.

Reducing Vaccination Disparities During a National Emergency Response: The US Mpox Vaccine Equity Pilot Program.

CONTEXT: In response to the first reported mpox cases in May 2022, the US government implemented plans to bring testing, treatment, and vaccines to communities disproportionately affected by mpox-including the population of men who have sex with men (MSM) and Black/African American and Hispanic/Latino men, 2 subpopulations experiencing vaccination disparities. We describe the development and implementation of the US Mpox Vaccine Equity Pilot Program (MVEPP), characteristics of completed vaccination projects, and challenges that occurred. We also discuss opportunities for reducing vaccination disparities in future outbreaks. PROGRAM: To address reported vaccination disparities, the US government launched MVEPP in 2 phases. Phase 1 centered around public events attended by large numbers of gay, bisexual, and other MSM, such as Pride festivals. Phase 2 asked health departments to propose mpox vaccination projects specifically aimed at reducing or eliminating racial/ethnic and other demographic disparities in mpox vaccination. IMPLEMENTATION: MVEPP received 35 vaccination project proposals. We analyzed data from 22 completed projects that resulted in 25 675 doses of JYNNEOS administered. We note 3 innovative strategies that were implemented in several projects: direct collaboration with organizations providing services to MSM and transgender women; implementation of MVEPP projects in unique nonclinical community settings and at venues frequented by MSM and transgender women; and offering an array of services as part of mpox vaccination projects, rather than offering only mpox vaccination. EVALUATION: MVEPP highlighted the importance of recognizing and working to eliminate racial/ethnic and other disparities in access to medical countermeasures during a public health emergency. Jurisdictions developed and implemented innovative strategies to bring mpox vaccination and related services to communities disproportionately affected by mpox-including MSM and the subpopulations of Black/African American and Hispanic/Latino MSM. Lessons learned from MVEPP may inform efforts to reduce disparities during future public health responses.

Tratamiento y prevención de la viruela del mono / Treatment and prevention of monkeypox

La viruela del mono es una zoonosis que se contagia principalmente a través del contacto directo con los fluidos y las lesiones cutáneas de personas contagiadas con vesículas aun activas. Aunque el virus fue aislado por primera vez en 1958, y el primer caso humano se identificó en un niño en 1970, en la República Democrática del Congo, la enfermedad ha aumentado progresivamente su incidencia en África, alcanzando en mayo de 2022 transmisión sostenida fuera de este continente. Al ser un virus de nueva introducción en nuestro entorno sanitario, es necesario aprender el patrón epidemiológico en un medio diferente al de las zonas tradicionalmente endémicas y conocer los tratamientos antivirales a nuestro alcance, así como las medidas profilácticas que podrían plantearse, sabiendo que como virus emergente en nuestras regiones las evidencias científicas aun son limitadas. Existen antivirales que han demostrado en modelos animales combatir eficazmente la enfermedad con muy buena tolerancia clínica. Esta enfermedad también ha obligado a revisar las características de las vacunas frente a la viruela, ya que han demostrado un efecto protector frente a la viruela del mono. Por ello, es importante disponer de un documento que recopile toda la información científica publicada a este respecto.(AU)

Monkeypox is a zoonosis that is spread mainly through direct contact with fluids and skin lesions of infected people with vesicles still active. Although the virus was isolated for the first time in 1958 and the first human case was identified in a child in 1970, in the Democratic Republic of the Congo, the disease has progressively increased its incidence in Africa reaching in May 2022 sustained transmission outside this continent. As it is a newly introduced virus in our health system, it is necessary to learn the epidemiological pattern in a different environment from that of traditionally endemic areas and to know the available antiviral treatments, as well as the prophylactic measures that could be considered, knowing that as a virus emerging in our regions, scientific evidence is still limited. There are antivirals that have been shown, in animal models, to effectively combat the disease with very good clinical tolerance. This disease has also forced us to review the characteristics of smallpox vaccines, because they have shown a protective effect against monkeypox. For this reason, it is important to have a document that compiles all the scientific information published in this regard.(AU)

La viruela sísmica aspectos relacionados a la fisiopatología, genoma, patogénesis, transmisión, replicación e inmunología / Aspects Related to pathophysiology, Genome, Pathogenesis, Transmission, Replication and Immunology of Monkeypox

Introducción: La viruela símica es una enfermedad zoonótica identificada por primera vez en 1958. El virus es un miembro del género Orthopoxvirus, de la familia Poxviridae. Infecta a una amplia variedad de mamíferos y se desconoce su reservorio natural. Objetivos: Describir los aspectos importantes relacionados a la fisiopatología, genoma, patogénesis, transmisión, replicación e inmunología de la viruela símica. Métodos: Se realizó una búsqueda de artículos originales, reportes de casos, revisiones bibliográficas y sistemáticas en el Portal Regional de la BVS, PubMed, Science, Nature y Lancet. Se consultaron los informes de la Organización Mundial de la Salud y la Organización Panamericana de la Salud sobre la viruela símica. Resultados: La propagación del virus de la viruela símica puede ocurrir a través del contacto cercano con lesiones, fluidos corporales, gotitas respiratorias y objetos contaminados. Una vez dentro del organismo, el virus infecta mucosas, células epiteliales y células inmunitarias de los tejidos adyacentes. El virus se replica y disemina rápidamente a través del sistema hemático y linfático. Las células T desempeñan un papel importante en la regulación de la respuesta inmunitaria contra el virus. Sin embargo, los Orthopoxvirus han desarrollado varios mecanismos para la evasión de la respuesta inmunitaria. Conclusiones: Los aspectos importantes descritos que se tuvieron en cuenta acerca de la transmisión de la viruela símica han tenido cambio significativo con el tiempo. El brote mundial de viruela símica de 2022 presentó una cadena de transmisión principalmente entre humanos asociada al contacto sexual(AU).

Introduction: Monkeypox is a zoonotic disease that was first identified in 1958. The virus is a member of Orthopoxvirus genus, of Poxviridae family. It infects wide variety of mammals and its natural reservoir is unknown. Objectives: To describe the important aspects related to pathophysiology, genome, pathogenesis, transmission, replication and immunology of monkeypox. Methods: A search of original articles, case reports, bibliographic and systematic reviews was carried out in VHL Regional Portal, PubMed, Science, Nature and Lancet. Reports from the World Health Organization and the Pan American Health Organization on monkeypox were consulted. Results: Spread of monkeypox virus can occur through close contact with lesions, body fluids, respiratory droplets, and contaminated objects. Once inside the body, the virus infects mucous membranes, epithelial cells and immune cells of adjacent tissues. The virus replicates and spreads rapidly through the blood and lymphatic system. T cells play an important role in regulating the immune response against the virus. However, Orthopoxviruses have developed several mechanisms to evade the immune response. Conclusions: The important aspects described, taken into account about monkeypox transmission, have significantly changed over time. 2022 global monkeypox outbreak presented a chain of transmission primarily among humans associated with sexual contact(AU)

Mpox (formerly monkeypox): pathogenesis, prevention, and treatment.

In 2022, a global outbreak of Mpox (formerly monkeypox) occurred in various countries across Europe and America and rapidly spread to more than 100 countries and regions. The World Health Organization declared the outbreak to be a public health emergency of international concern due to the rapid spread of the Mpox virus. Consequently, nations intensified their efforts to explore treatment strategies aimed at combating the infection and its dissemination. Nevertheless, the available therapeutic options for Mpox virus infection remain limited. So far, only a few numbers of antiviral compounds have been approved by regulatory authorities. Given the high mutability of the Mpox virus, certain mutant strains have shown resistance to existing pharmaceutical interventions. This highlights the urgent need to develop novel antiviral drugs that can combat both drug resistance and the potential threat of bioterrorism. Currently, there is a lack of comprehensive literature on the pathophysiology and treatment of Mpox. To address this issue, we conducted a review covering the physiological and pathological processes of Mpox infection, summarizing the latest progress of anti-Mpox drugs. Our analysis encompasses approved drugs currently employed in clinical settings, as well as newly identified small-molecule compounds and antibody drugs displaying potential antiviral efficacy against Mpox. Furthermore, we have gained valuable insights from the process of Mpox drug development, including strategies for repurposing drugs, the discovery of drug targets driven by artificial intelligence, and preclinical drug development. The purpose of this review is to provide readers with a comprehensive overview of the current knowledge on Mpox.

Manejo desde atención primaria de la infección por la viruela del mono (MPOX) en humanos / Management from Primary Care of monkeypox infection (MPOX) in humans

La viruela del mono (MPOX) es una zoonosis vírica endémica en países de África occidental o central que esporádicamente se exporta a otras regiones. En mayo del 2022, comenzó a ocurrir un brote mundial de viruela MPOX en varias naciones de Europa y Norteamérica. La mayoría de los casos notificados se identificaron a nivel ambulatorio y afectaron principalmente a hombres que tienen sexo con hombres (HSH). El contagio es por contacto estrecho con lesiones, líquidos corporales, secreciones respiratorias o con material contaminado, de persona o animal infectado. El cuadro clínico es similar a la viruela humana, con menor gravedad. Predomina la afectación cutánea leve y autolimitada tras dos a cuatro semanas. En HSH aparecen lesiones cutáneas atípicas debido a la manera de contagio. En ciertos grupos de riesgo pueden presentarse formas graves o complicaciones. La tasa de letalidad es de 3 a 6% según el clado responsable. El diagnóstico de sospecha se confirma con la detección del virus, a partir de exudados de las lesiones o costras, con técnicas de amplificación de ácidos nucleicos mediante reacción en cadena de la polimerasa (PCR) convencional o en tiempo real. El manejo clínico en la mayoría de los casos se realiza desde atención primaria (AP), mediante el control de los principales síntomas. Entre 5 a 10% requieren un manejo hospitalario y existen algunas opciones de tratamiento antiviral específico. Las vacunas frente a la viruela humana protegen contra la MPOX y se utilizan como profilaxis pre y posexposición a personas de riesgo. Las medidas para reducir la exposición al virus, es la principal estrategia de prevención de la MPOX. Además, el papel del médico de familia es clave para controlar la propagación del virus de la MPOX mediante la vigilancia activa y el diagnóstico temprano de la enfermedad.(AU)

Monkeypox (MPOX) is a viral zoonosis endemic in West or Central African countries that is sporadically exported to another area. In May 2022, a global outbreak of MPOX smallpox began to occur in several countries in Europe and North America. Most of the reported cases are identified at the outpatient level and mainly affect men who have sex with men (MSM). Transmission is by close contact with lesions, body fluids, respiratory secretions or contaminated material from an infected person or animal. The clinical picture is similar to human smallpox, with less severity. Mild, self-limiting skin involvement predominates after 2-4 weeks. In MSM, atypical skin lesions appear due to the mode of infection. Severe forms or complications may appear in certain risk groups. The case fatality rate is 3%-6% depending on the clade responsible. The diagnosis of suspicion is confirmed by detection of the virus from exudates of lesions or scabs, with nucleic acid amplification techniques by conventional or real-time PCR. Clinical management in most cases is performed in primary care (PC), by monitoring the main symptoms. Between 5-10% require hospital management and there are some specific antiviral treatment options. Human smallpox vaccines protect against MPOX and are used as pre- and post-exposure prophylaxis for persons at risk. Measures to reduce exposure to the virus are the main MPOX prevention strategy. In addition, the role of the family physician is key to controlling the spread of MPOX through active surveillance and early diagnosis of the disease.(AU)

La viruela símica como enfermedad zoonótica viral y reemergente en el actual contexto sanitario mundial / Mpox as a Viral Zoonotic Disease Reemerging in the Current Global Health Context

Introducción: La viruela símica es una enfermedad zoonótica que también se trasmite de persona a persona por contacto estrecho. En el brote actual hasta el 31 de agosto de 2022 se reportaban 50 496 casos diagnosticados en 101 países, por lo que se consideró una situación preocupante por la Organización Mundial de la Salud. Objetivo: Exponer información actualizada sobre la viruela símica en el contexto sanitario actual. Métodos: Se realizó una búsqueda de literatura científica en las bases de datos ScienceDirect, PubMed/Medline, SciELO y Google Académico, mediante los descriptores o palabras relacionadas con la enfermedad, para encontrar revisiones, comunicados, informes, distintos artículos de revistas, entre otros documentos especializados de producción científica. Se seleccionó un total de 30 citas, actualizadas en su totalidad. Desarrollo: Desde su identificación en humanos se han reportado brotes de viruela símica en varios países; el más preocupante, ha sido el de reciente declaración en 2022, debido a la presencia de casos en países no endémicos, con un alcance geográfico extenso. Las manifestaciones clínicas pueden cursar con síntomas leves, como erupciones en la cara y el resto del cuerpo, fiebre, cefalea, mialgias y fatiga, por lo que no constituye una enfermedad potencialmente mortal; sin embargo, de presentarse comorbilidades la evolución podría ser tórpida. Conclusiones: La presencia de casos de viruela símica en humanos se ha mantenido desde su aparición, sin encontrar un tratamiento específico y vacunas autorizadas para su administración, lo que podría generar un aumento de contagios y fallecidos(AU)

Introduction: Mpox is a zoonotic disease also transmitted from person to person by close contact. The current outbreak, up to August 31, 2022, reported 50 496 diagnosed cases from 101 countries; therefore; it was considered a situation of concern by the World Health Organization. Objective: To present updated information on Mpox in the current health context. Methods: A scientific literature search was carried out in the databases ScienceDirect, PubMed/Medline, SciELO and Google Scholar, using descriptors or words related to the disease, in order to find reviews, communications, reports, different journal articles, among other specialized documents of scientific production. A total of 30 entirely updated citations were selected. Development: Since Mpox was identified in humans, outbreaks of the disease have been reported in several countries; the most worrisome has been reported recently in 2022, due to the presence of cases in nonendemic countries, with an extensive geographical scope. The clinical manifestations may occur with mild symptoms, such as rash on the face or the rest of the body, fever, headache, myalgia and fatigue; therefore, it is not a potentially mortal disease. However, in case of comorbidity, the evolution could be torpid. Conclusions: Mpox cases in humans has been present since its appearance, without any specific treatment or vaccines authorized to be administered, which could generate an increase in contagions and deaths(AU)

Vacunas frente a la viruela del mono (monkeypox) / Vaccines against monkeypox

El virus de la viruela de los monos es un virus que presenta un 90% de homología genómica con el humano (smallpox), pero se trasmite de forma natural entre diferentes reservorios animales salvajes y es considerado una zoonosis. A lo largo del siglo XX se desarrollaron diferentes vacunas basadas en el poxvirus vaccinia que fueron utilizadas para la vacunación frente a la viruela humana. Tras la erradicación de la viruela humana estas vacunas dejaron de utilizarse. Las vacunas actuales frente a la viruela de los monos se clasifican por la OMS como replicativas (ACAM2000), mínimamente replicativas (LC16m8) y no replicativas (MVA-BN), siendo esta última la utilizada en la actualidad. La epidemia extraafricana de viruela de los monos de 2022ha puesto en evidencia la falta de vacunas de eficacia demostrada y de baja reactogenicidad. Se considera que la utilización de esta vacuna en el brote actual puede desempeñar un papel en la prevención o atenuación de la enfermedad como profilaxis preexposición en contactos estrechos de casos confirmados. (AU)

The monkeypox virus is a virus that has 90% genomic homology with the human (smallpox), but it is naturally transmitted between different wild animal reservoirs and is considered a zoonosis. Throughout the 20th century, different vaccines based on the vaccinia poxvirus were developed and used for vaccination against smallpox. After the eradication of smallpox, these vaccines were no longer used. Current vaccines against monkeypox virus are classified by the WHO as replicative (ACAM2000), minimally replicative (LC16m8) and non-replicative (MVA-BN), the latter being the one currently used. The 2022 extra-African monkeypox virus epidemic has highlighted the lack of vaccines with proven efficacy and low reactogenicity. It is considered that the use of this vaccine in the current outbreak may play a role in the prevention or attenuation of the disease as pre-exposure prophylaxis in close contacts of confirmed cases. (AU)