Smallpox, Monkeypox and Other Human Orthopoxvirus Infections

Shchelkunova, Galina A.; Щелкунов, С. Н.

doi:10.3390/v15010103

Cited by 29 publications

(20 citation statements)

References 120 publications

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“…The large-scale epidemic of monkeypox among humans that spread to all continents in 2022 (Harapan et al, 2022;Shchelkunova, Shchelkunov, 2023) has put the question about mass vaccination against this infection in the risk groups on the agenda. Important issues were the need to properly choose the type of vaccine and the optimal route of smallpox vaccine administration.…”

Section: Discussionmentioning

confidence: 99%

Smallpox vaccination in a mouse model

Shchelkunov,

Sergeev,

Pyankov

et al. 2023

Vestn. VOGiS

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The monkeypox epidemic, which became unusually widespread among humans in 2022, has brought awareness about the necessity of smallpox vaccination of patients in the risk groups. The modern smallpox vaccine variants are introduced either intramuscularly or by skin scarification. Intramuscular vaccination cannot elicit an active immune response, since tissues at the vaccination site are immunologically poor. Skin has evolved into an immunologically important organ in mammals; therefore, intradermal delivery of a vaccine can ensure reliable protective immunity. Historically, vaccine inoculation into scarified skin (the s.s. route) was the first immunization method. However, it does not allow accurate vaccine dosing, and high-dose vaccines need to be used to successfully complete this procedure. Intradermal (i.d.) vaccine injection, especially low-dose one, can be an alternative to the s.s. route. This study aimed to compare the s.s. and i.d. smallpox immunization routes in a mouse model when using prototypic second- and fourth-generation low-dose vaccines (104 pfu). Experiments were conducted using BALB/c mice; the LIVP or LIVP-GFP strains of the vaccinia virus (VACV) were administered into the tail skin via the s.s. or i.d. routes. After vaccination (7, 14, 21, 28, 42, and 56 days post inoculation (dpi)), blood samples were collected from the retro-orbital venous sinus; titers of VACV-specific IgM and IgG in the resulting sera were determined by ELISA. Both VACV strains caused more profound antibody production when injected via the i.d. route compared to s.s. inoculation. In order to assess the level of the elicited protective immunity, mice were intranasally infected with a highly lethal dose of the cowpox virus on 62 dpi. The results demonstrated that i.d. injection ensures a stronger protective immunity in mice compared to s.s. inoculation for both VACV variants.

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Section: Discussionmentioning

confidence: 99%

Smallpox vaccination in a mouse model

Shchelkunov,

Sergeev,

Pyankov

et al. 2023

Vestn. VOGiS

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“…As an example, the members of the Capripoxvirus genus LSDV, goat poxvirus and sheep poxvirus, are known to elicit cross-protective immune responses [ 109 ]. Similarly, in the genus Orthopoxvirus , Vaccinia, cowpox virus, monkeypox virus, and variola (smallpox) virus generate cross-protective immune responses [ 110 ]. As a consequence of the importance of the orthopoxviruses to human medicine, there is a larger body of scientific literature underpinning vaccine development.…”

Section: Development Of Mrna Vaccines For Important Livestock Diseasesmentioning

confidence: 99%

Can the Revolution in mRNA-Based Vaccine Technologies Solve the Intractable Health Issues of Current Ruminant Production Systems?

Mahony,

Briody,

Ommeh

2024

Vaccines

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To achieve the World Health Organization’s global Sustainable Development Goals, increased production of high-quality protein for human consumption is required while minimizing, ideally reducing, environmental impacts. One way to achieve these goals is to address losses within current livestock production systems. Infectious diseases are key limiters of edible protein production, affecting both quantity and quality. In addition, some of these diseases are zoonotic threats and potential contributors to the emergence of antimicrobial resistance. Vaccination has proven to be highly successful in controlling and even eliminating several livestock diseases of economic importance. However, many livestock diseases, both existing and emerging, have proven to be recalcitrant targets for conventional vaccination technologies. The threat posed by the COVID-19 pandemic resulted in unprecedented global investment in vaccine technologies to accelerate the development of safe and efficacious vaccines. While several vaccination platforms emerged as front runners to meet this challenge, the clear winner is mRNA-based vaccination. The challenge now is for livestock industries and relevant stakeholders to harness these rapid advances in vaccination to address key diseases affecting livestock production. This review examines the key features of mRNA vaccines, as this technology has the potential to control infectious diseases of importance to livestock production that have proven otherwise difficult to control using conventional approaches. This review focuses on the challenging diseases of ruminants due to their importance in global protein production. Overall, the current literature suggests that, while mRNA vaccines have the potential to address challenges in veterinary medicine, further developments are likely to be required for this promise to be realized for ruminant and other livestock species.

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“…Among these, the variola virus, the causative agent of smallpox, was responsible for millions of deaths throughout history ( 1 , 2 ). Other members, such as monkeypox (Mpox), cowpox (CPXV), and vaccinia (VACV), exhibit sporadic occurrences worldwide, with a recent, comprehensive outbreak of Mpox responsible for over 80,000 cases as of January 2023 (according to the Centers for Disease Control and Prevention ) ( 1 ). Outbreaks of different VACV strains have also increased in the last 20 y in different areas of the world.…”

Section: Introductionmentioning

confidence: 99%

Generation of recombinant mAbs to vaccinia virus displaying high affinity and potent neutralization

Noy-Porat,

Tamir,

Alcalay

et al. 2023

Microbiol Spectr

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Members of the Orthopoxvirus genus can cause severe infections in humans. Global vaccination against smallpox, caused by the variola virus, resulted in the eradication of the disease in 1980. Shortly thereafter, vaccination was discontinued, and as a result, a large proportion of the current population is not protected against orthopoxviruses. The concerns that the variola virus or other engineered forms of poxviruses may re-emerge as bioweapons and the sporadic outbreaks of zoonotic members of the family, such as Mpox, which are becoming more frequent and prevalent, also emphasize the need for an effective treatment against orthopoxviruses. To date, the most effective way to prevent or control an orthopoxvirus outbreak is through vaccination. However, the traditional vaccinia-based vaccine may cause severe side effects. Vaccinia immune globulin was approved by the U.S. Food and Drug Administration (FDA) for the treatment of vaccine adverse reactions and was also used occasionally for the treatment of severe orthopoxvirus infections. However, this treatment carries many disadvantages and is also in short supply. Thus, a recombinant alternative is highly needed. In this study, two non-human primates were immunized with live vaccinia virus, producing a robust and diverse antibody response. A phage-display library was constructed based on the animal’s lymphatic organs, and a panel of neutralizing monoclonal antibodies (mAbs), recognizing diverse proteins of the vaccinia virus, was selected and characterized. These antibodies recognized both mature virion and enveloped virion forms of the virus and exhibited high affinity and potent in vitro neutralization capabilities. Furthermore, these monoclonal antibodies were able to neutralize Mpox 2018 and 2022 strains, suggesting a potential for cross-species protection. We suggest that a combination of these mAbs has the potential to serve as recombinant therapy both for vaccinia vaccine adverse reactions and for orthopoxvirus infections. IMPORTANCE In this manuscript, we report the isolation and characterization of several recombinant neutralizing monoclonal antibodies (mAbs) identified by screening a phage-display library constructed from lymphatic cells collected from immunized non-human primates. The antibodies target several different antigens of the vaccinia virus, covering both mature virion and extracellular enveloped virion forms of the virus. We document strong evidence indicating that they exhibit excellent affinity to their respective antigens and, most importantly, optimal in vitro neutralization of the virus, which exceeded that of vaccinia immune globulin. Furthermore, we present the ability of these novel isolated mAbs (as well as the sera collected from vaccinia-immunized animals) to neutralize two Mpox strains from the 2018 to 2022 outbreaks. We believe that these antibodies have the potential to be used for the treatment of vaccinia vaccine adverse reactions, for other orthopoxvirus infections, and in cases of unexpected bioterror scenarios.

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Smallpox, Monkeypox and Other Human Orthopoxvirus Infections

Cited by 29 publications

References 120 publications

Smallpox vaccination in a mouse model

Smallpox vaccination in a mouse model

Can the Revolution in mRNA-Based Vaccine Technologies Solve the Intractable Health Issues of Current Ruminant Production Systems?

Generation of recombinant mAbs to vaccinia virus displaying high affinity and potent neutralization

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