Overview of mRNA Vaccines in Preventing Mpox Infections

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Overview of mRNA Vaccines in Preventing Mpox Infections

Overview of mRNA Vaccines in Preventing Mpox Infections

Abstract:

Human Mpox virus (Mpox) is classified under the Poxviridae family, specifically within the Orthopoxvirus genus. Mpox contains double-stranded DNA and is known to have two genetic lineages: the West African and Central African (Congo Basin) lineages.

Mpox can be treated or prevented through smallpox vaccination or therapeutic agents. The modification of smallpox vaccines for Mpox prevention has proven beneficial due to the strong correlation between the smallpox and Mpox viruses, which belong to the same family.

The two FDA-approved smallpox vaccines (ACAM2000 and JYNNEOS) have shown effective cross-protection against Mpox.

However, ACAM2000 has significant potential side effects, such as heart-related issues, whereas JYNNEOS poses a lower risk. Despite the discontinuation of smallpox vaccines for over 40 years, Mpox has reemerged with altered characteristics.

The safety and efficacy of leading mRNA vaccines against SARS-CoV-2 and its variants have been demonstrated in clinical trials and subsequent data analysis. The first mRNA therapeutic model involves injecting messenger RNA into patients to produce target proteins and trigger an immune response.

The potential for highly effective, safe administration, low-cost manufacturing, and rapid development are some benefits of RNA vaccines, offering a viable alternative to traditional vaccines.

mRNA vaccines are highly effective in preventing Mpox infections and may eventually replace existing whole-virus vaccines.

This paper aims to provide an overview of the ongoing research, development, and testing of Mpox mRNA vaccines.

Overview of mRNA Vaccines in Preventing Mpox Infections

Introduction

Mpox is a relatively uncommon member of the Poxviridae family and the Orthopoxvirus genus. It has two genetically distinct lineages: the West African and Central African (Congo Basin) lineages, with Mpox having a double-stranded DNA (dsDNA) genome.

The virus was first discovered in monkeys in 1958 at the Copenhagen Serum Institute, hence the name “Mpox.” The first human Mpox infection was diagnosed in August 1970 in a 9-year-old boy with a fever at Basankusu Hospital in the Democratic Republic of Congo (DRC).

Mpox made its first appearance outside Africa in the U.S. Midwest in 2003, where prairie dogs were identified as the reservoirs rather than monkeys or squirrels.

The virus was transmitted to prairie dogs through infected Gambian pouched rats imported from Ghana, which eventually led to human cases in the U.S.

The evolution of Mpox and its diversification across Africa remain largely unknown. The World Health Organization (WHO) reported that as of July 20, 2022, following the first confirmed case in the UK in May 2022, the Mpox outbreak had spread to over 82 locations.

A study on the epidemiology of the 2022 Madrid outbreak reported 508 confirmed human Mpox cases within the first five weeks, with nearly all cases (99%) occurring in men who have sex with men (MSM).

Symptoms included rashes primarily on the genital, perineal, or perianal regions, and lymph node enlargement in the groin area, suggesting close physical contact during sexual activity as a significant transmission route in this outbreak.

A new Mpox pandemic was detected across all six WHO regions in May 2022, and WHO declared it a public health emergency on July 23, 2022.

Before the current pandemic, Mpox had been documented in various parts of Central and West Africa. Most Mpox cases outside Africa were linked to international travel to endemic regions or the importation of infected animals.

The decrease in immunity from smallpox vaccination has made Mpox a potential global health threat. While Mpox does not usually cause significant mortality in individuals with healthy immune systems, severe illness and death can occur in immunocompromised individuals, children, the elderly, pregnant women, or those with comorbidities such as diabetes. It is estimated that 95% of Mpox infections are transmitted through close contact.

Approximately 41% of those infected with HIV were identified as gay or bisexual men, representing 98% of Mpox cases. By 2022, 3-6% of confirmed Mpox cases had resulted in death.

The first recorded Mpox case outside Africa occurred in the U.S. Midwest in 2003, with 71 people infected but no fatalities reported. In 2005, 49 cases were recorded in Sudan, though genetic analysis later suggested the virus likely originated from the DRC rather than Sudan.

Africa has recorded more Mpox cases, with the DRC reporting around 2,000 cases annually from 2011 to 2014. In September 2017, 118 confirmed cases were recorded, and in September 2018, the first case was reported in the UK.

Since May 2022, the current outbreak has spread to non-endemic regions across Europe, Oceania, Asia, and the Americas.

Over 16,000 people in more than 70 countries have been confirmed dead, with a current mortality rate of 0.03%.

The global spread of the virus has been attributed to the importation or international transport of infected animals from affected countries.

The outbreak of Mpox clusters worldwide has drawn attention from WHO and prompted international health organizations to maintain high vigilance and cooperation.

Preliminary results from genomic sequencing of Mpox DNA isolates circulating in different countries suggest that the outbreak affecting multiple nations may be attributed to the West African lineage.

Notably, the Mpox genome sequences obtained from various countries differ from those of the West African lineage, although further research is needed to determine the impact of these mutations or genomic changes on the virus’s transmissibility, virulence, and immune evasion. Although Mpox symptoms typically last two to four weeks and are self-limiting, severe cases may occur, with a mortality rate of 3% to 10%.

However, only certain licensed drugs and vaccines are given to those with severe illness or compromised immune systems. Currently, no effective and safe treatment exists for Mpox infections.

The cessation of smallpox vaccination in most communities and countries has led to decreased immunity.

While there is evidence that smallpox vaccines can provide 85% protection against Mpox, no vaccinations have been provided since WHO declared smallpox eradicated in 1980.

Furthermore, transplacental transmission in pregnant women has been linked to congenital Mpox, which may manifest during childbirth and in newborns.

The duration of protection remains unclear. If vaccination reduces Mpox transmission, outbreaks will be controlled, preventing further spread within and outside the initial high-risk groups.

Current Treatments and Research

Antiviral treatment for individuals infected with pathogenic Orthopoxvirus will provide immediate benefits, as vaccine protection is delayed. The effectiveness of antiviral drugs in controlling outbreaks has yet to be tested, as they were unavailable during the smallpox eradication campaign.

Antiviral therapy will undoubtedly benefit treating unvaccinated Mpox patients and controlling the spread of the disease. Various nucleic acid detection techniques have also been developed to detect and characterize Mpox.

DNA polymerase (E9L) and envelope protein (B6R) are two Orthopoxvirus genes targeted in experiments. Currently, no specific treatments for Mpox-related diseases have been approved by the U.S. Food and Drug Administration (FDA).

However, several antiviral drugs (Tecovirimat, Cidofovir, Brincidofovir, and intravenous vaccinia immune globulin [VIGIV]) developed for smallpox treatment are now used to treat Mpox. Yet, there is no information regarding their efficacy in treating Mpox infections.

Given WHO’s declaration of Mpox as a global public health emergency, countries must prioritize timely and comprehensive evaluation of vaccine efficacy and effectiveness to ensure readiness for rapid vaccination implementation.

On June 24, 2022, WHO issued interim guidance on Mpox vaccination, emphasizing that widespread vaccination is not currently needed or recommended. Collaboration in vaccine efficacy studies, using standardized procedures and data collection methods, is essential.

WHO places great importance on supporting vaccination initiatives, including monitoring and contact tracing. WHO also emphasizes the need for effective public health communication and robust pharmacovigilance in this specific context.

The JYNNEOS vaccine has been approved for smallpox and Mpox prevention during the current outbreak in the U.S. JYNNEOS can be substituted with ACAM2000, which is approved to help prevent smallpox and Mpox. In phase III clinical trials, the modified vaccinia Ankara (MVA) virus has shown favorable safety.

However, it is essential to note that larger-scale vaccine studies are needed before MVA can be licensed for general use as a preventive measure against smallpox and Mpox infections. Pricing of the product is a factor to consider.

Thus, post-exposure vaccination with ACAM2000 or MVA remains the preferred option for Mpox and smallpox. Despite their potential, ACAM2000 and MVA vaccines have yet to meet global medical needs.

New research indicates that using JYNNEOS vaccination has only partially increased neutralizing antibodies (nABs) against Mpox.

Therefore, there is an urgent need for a safe, effective, and readily available specific Mpox vaccine to combat the current Mpox outbreak.

Using nucleic acid vaccines can develop a safe and effective vaccine against this disease. Large-scale vaccine production is also easy and cost-effective.

mRNA vaccines offer many advantages in preventing viral infections, including their ability to be quickly synthesized and mass-produced, an excellent safety record without nuclear input, and their efficacy in stimulating both humoral and cellular immune responses.

Once inside, cells interpret mRNA as a set of instructions and build proteins that bind to antigens on the pathogen.

The immune system recognizes these foreign antigens as invaders, mobilizes defenses known as antibodies (ABs) and T cells, and prepares the immune system for potential future attacks.

Researchers at Stanford University School of Medicine have found that the Pfizer/BioNTech mRNA vaccine designed to combat the original SARS-CoV-2 strain also induces a weaker neutralizing response against a protein variant of the original SARS-CoV-2 strain.

The breakthrough of COVID-19 vaccines in a limited time demonstrates the advantages of mRNA vaccines, making them viable candidates for Mpox prevention.

However, developing and testing vaccines based on mRNA technology for other viruses are limited.

Even as mRNA vaccines continue to protect against COVID-19 infection, their application to viruses, such as Mpox, that have not yet been effectively controlled by traditional methods remains unknown.

mRNA-based vaccines could be one of the best approaches to addressing the current Mpox outbreak.

Conclusion

This article reviews the ongoing research, development, and testing of mRNA vaccines for preventing Mpox infections. mRNA vaccines against SARS-CoV-2 and its variants have shown high efficacy in clinical trials and subsequent data analysis.

A high level of safety and efficacy has been demonstrated in various contexts for SARS-CoV-2 mRNA vaccines. The first mRNA therapeutic model involves injecting messenger RNA into patients to produce target proteins and trigger an immune response.

The potential for highly effective, safe administration, low-cost manufacturing, and rapid development are some benefits of RNA vaccines, offering a viable alternative to traditional vaccines.

This paper highlights mRNA vaccines as a safe and effective measure to prevent Mpox infections. It suggests that mRNA vaccines may eventually replace existing whole-virus vaccines.

Acknowledgment: The researchers received no financial support from any third-party funding agency, nor was there any conflict of interest.