In-silico formulation of a next-generation polyvalent vaccine against multiple strains of monkeypox virus and other related poxviruses
Abu Tayab MoinNurul Amin RaniRajesh B. PatilTanjin Barketullah RobinMd. Asad UllahZahidur RahimMd. Foyzur RahmanTalha ZubairMohabbat HossainA. K. M. Moniruzzaman MollahNurul AbsarMahboob HossainMohammed Abul ManchurNazneen Naher Islam
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Abstract:
Mpox (formerly known as monkeypox) virus and some related poxviruses including smallpox virus pose a significant threat to public health, and effective prevention and treatment strategies are needed. This study utilized a reverse vaccinology approach to retrieve conserved epitopes for monkeypox virus and construct a vaccine that could provide cross-protection against related viruses with similar antigenic properties. The selected virulent proteins of monkeypox virus, MPXVgp165, and Virion core protein P4a, were subjected to epitope mapping for vaccine construction. Two vaccines were constructed using selected T cell epitopes and B cell epitopes with PADRE and human beta-defensins adjuvants conjugated in the vaccine sequence. Both constructs were found to be highly antigenic, non-allergenic, nontoxic, and soluble, suggesting their potential to generate an adequate immune response and be safe for humans. Vaccine construct 1 was selected for molecular dynamic simulation studies. The simulation studies revealed that the TLR8-vaccine complex was more stable than the TLR3-vaccine complex. The lower RMSD and RMSF values of the TLR8 bound vaccine compared to the TLR3 bound vaccine suggested better stability and consistency of hydrogen bonds. The Rg values of the vaccine chain bound to TLR8 indicated overall stability, whereas the vaccine chain bound to TLR3 showed deviations throughout the simulation. These results suggest that the constructed vaccine could be a potential preventive measure against monkeypox and related viruses however, further experimental validation is required to confirm these findings.Keywords:
Monkeypox
Reverse vaccinology
Attenuated vaccine
The use of classical smallpox vaccines based on vaccinia virus (VV) is associated with severe complications in both naive and immune individuals. Modified vaccinia virus Ankara (MVA), a highly attenuated replication-deficient strain of VV, has been proven to be safe in humans and immunocompromised animals, and its efficacy against smallpox is currently being addressed. Here we directly compare the efficacies of MVA alone and in combination with classical VV-based vaccines in a cynomolgus macaque monkeypox model. The MVA-based smallpox vaccine protected macaques against a lethal respiratory challenge with monkeypox virus and is therefore an important candidate for the protection of humans against smallpox.
Monkeypox
Smallpox vaccine
Poxviridae
Modified vaccinia Ankara
Orthopoxvirus
Variola virus
Smallpox virus
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Today, the World Health Organization has declared a global health emergency, caused by the Monkeypox outbreak. In the monthly analysis for June, 3500 cases have been reported in 50 countries around the world. In the analysis for July, more than 30000 cases have been reported in 75 countries. Thus, in the circumstances of the continuing COVID-19 pandemic, the appearance and dynamics of spreading of Monkeypox is alarming. In this paper, for the first time, elemental composition of Poxvirus, Monkeypox virus, and Vaccinia virus have been reported. Additionally, thermodynamic properties have been reported for nucleic acids, nucleocapsids, and entire virus particles. The similarity in chemical composition and thermodynamic properties of the analyzed viruses has been used to explain the crossed immunity to Poxviruses. Finally, binding thermodynamic properties have been reported for the Vaccinia virus.
Monkeypox
Orthopoxvirus
Variola virus
Smallpox vaccine
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Monkeypox was first discovered in 1958 when two outbreaks of a pox-like disease occurred in colonies of monkeys kept for research. The first human case of monkeypox was recorded in 1970. Since then, monkeypox has been reported in people in several other central and western African countries. Prior to the 2022 outbreak, nearly all monkeypox cases in people outside of Africa were linked to international travel to countries where the disease commonly occurs, or through imported animals.1 It’s not clear how the people were exposed to monkeypox, but early data suggest that gay, bisexual, and other men who have sex with men make up a high number of cases. However, anyone who has been in close contact with someone who has monkeypox is at risk. Monkeypox is a viral zoonosis (a virus transmitted to humans from animals) with symptoms similar to those seen in the past in smallpox patients, although it is clinically less severe. With the eradication of smallpox in 1980 and subsequent cessation of smallpox vaccination, monkeypox has emerged as the most important orthopoxvirus for public health. Monkeypox primarily occurs in central and west Africa, often in proximity to tropical rainforests, and has been increasingly appearing in urban areas. Animal hosts include a range of rodents and non-human primates.1
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Orthopoxvirus
Smallpox vaccine
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Serological surveillance of suspected orthopoxvirus infections in man is important for confirming the success of the worldwide smallpox eradication programme. An adsorption radioimmunoassay (RIA) was used to differentiate sera from patients who were naturally infected with human monkeypox or variola virus, and individuals who were immunized with vaccinia virus. The antisera were adsorbed with uninfected chicken chorioallantoic membrane (CAM) and vaccinia-infected CAM before reacting in RIA with vaccinia, monkeypox, and variola antigens. Each serum group showed characteristic patterns of residual antibody activity which made it possible to identify antibody specificities.When 45 human sera were tested by this method, 71% were identified as having vaccinia, variola, or monkeypox adsorption characteristics, while the remaining 29% could not be identified. Of the identified sera, 9 were characteristic of vaccinia, 8 of variola, and 15 of monkeypox. Six of the 15 monkeypox sera were virologically confirmed monkeypox infections, 6 were suspected monkeypox infections but were not virologically confirmed, and 3 were of unknown aetiology.The adsorption RIA provides a method of identifying serologically the poxvirus responsible for infection long after the acute phase of illness.
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Orthopoxvirus
Variola virus
Poxviridae
Cowpox
Smallpox vaccine
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Laboratory tests have confirmed an outbreak of monkeypox virus in the United States. Monkeypox is a rare viral disease that is allied to smallpox but is less lethal. It occurs mostly in central and western …
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Orthopoxvirus
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Monkeypox infection is caused by a virus of the genus Orthopoxvirus, a member of the Poxviridae family. Monkeypox virus is transmitted from individual to individual through contact with lesions, body fluids, and respiratory droplets. The infection caused by monkeypox is usually a self-limited disease with mild symptoms lasting 2 to 4 weeks. Monkeypox typically presents with fever, rash, and enlarged lymph nodes. New vaccines have recently been authorized for the prevention of monkeypox infection, whereas there are no specific pharmacological antiviral treatments for monkeypox infection. However, because the viruses which cause adult smallpox and monkeypox are similar, antiviral drugs developed in the past have also shown efficacy against monkeypox. In this review, we highlight the in vitro and clinical evidence found in the literature on the efficacy and safety of pharmacological agents with antiviral activity against monkeypox infection and the different regulatory aspects of countries.
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Orthopoxvirus
Poxviridae
Cowpox
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Monkeypox has been discovered in most of the US, except a few states, according to the US Centers for Disease Control and Prevention. The states with the most occurrences are Florida, New York, California, Illinois, and Illinois. It was first observed in laboratory monkeys in Copenhagen, Denmark, in 1958, and was later recognized as a distinct illness. Numerous animal species are thought to act as a natural reservoir for the virus. Monkeypox was first identified in colonies of captive monkeys after two outbreaks of a disease that resembled the pox. The cause of the illness, known as "monkeypox," is still unknown. However, the virus can infect humans if it is carried by nonhuman primates (such as monkeys) or African rodents. These monkeypox viruses could be diagnosed using a variety of general methods. As a result, the researchers analyzed the symptoms of the monkeypox virus, an outbreak of the disease in various nations, risk factors for monkeypox infection, and several methods for monkeypox virus identification. This article also looks at the development of monkeypox virus cases in the month and year of May 2022.
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Natural reservoir
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Antigenicity
Reverse vaccinology
Peptide vaccine
Group-specific antigen
Epitope mapping
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Orthopoxvirus
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Laboratory tests have confirmed an outbreak of monkeypox in the United States. By 16 June nine cases had been confirmed and more than 80 were under investigation.
Monkeypox is a rare viral disease that is allied to smallpox but is less lethal and that occurs mostly in central and western Africa. It is called monkeypox because it was first found in 1958 in laboratory monkeys.
Early in June at least 20 cases from three midwestern states were reported to the federal Centers …
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Orthopoxvirus
Smallpox vaccine
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