Mpox Mutations Evading Vaccines and Spreading Faster
Author: University of Missouri-Columbia
Published: 2022/11/05 - Updated: 2025/08/28
Publication Details: Peer-Reviewed, Findings
Category Topic: Mpox Virus - Academic Publications
Page Content: Synopsis - Introduction - Main - Insights, Updates
Synopsis: This research, published as a peer-reviewed scholarly study in the Journal of Autoimmunity, reveals critical findings about how the mpox virus has evolved to become more infectious and resistant to current treatments. University of Missouri researchers analyzed DNA sequences from over 200 mpox virus strains spanning from 1965 to 2022, discovering that the virus has accumulated mutations specifically at sites where antiviral drugs and vaccine-induced antibodies are designed to bind. This comprehensive temporal analysis demonstrates how the virus has grown "smarter," developing mechanisms to evade therapeutic interventions while continuing to spread among the more than 77,000 people infected across 100+ countries. The findings are particularly valuable for vulnerable populations, including immunocompromised individuals, seniors, and people with disabilities who may face heightened risks from viral infections, as this research could lead to modified existing treatments or entirely new therapeutic approaches that account for these evolutionary changes and improve treatment effectiveness - Disabled World (DW).
Introduction
Mutations in the mpox virus replication complex: Potential contributing factors to the 2022 outbreak
Mpox has infected more than 77,000 people in more than 100 countries worldwide, and - similar to COVID-19 - mutations have enabled the virus to grow stronger and smarter, evading antiviral drugs and vaccines in its mission to infect more people.
Main Content
Now, a team of researchers at the University of Missouri has identified the specific mutations in the Mpox virus that contribute to its continued infectiousness. The findings could lead to several outcomes: modified versions of existing drugs used to treat people suffering from Mpox or the development of new drugs that account for the current mutations to increase their effectiveness at reducing symptoms and the spread of the virus.
Kamlendra Singh, a professor in the MU College of Veterinary Medicine and Christopher S. Bond Life Sciences Center principal investigator, collaborated with Shrikesh Sachdev, Shree Lekha Kandasamy, and Hickman High School student Saathvik Kannan to analyze the DNA sequences of more 200 strains of mpox virus spanning multiple decades, from 1965, when the virus first started spreading, to outbreaks in the early 2000s and again in 2022.
"By doing a temporal analysis, we were able to see how the virus has evolved, and a key finding was the virus is now accumulating mutations, specifically where drugs and antibodies from vaccines are supposed to bind," Sachdev said. "So, the virus is getting smarter; it can avoid being targeted by drugs or antibodies from our body's immune response and continue to spread to more people."
Needles in a Haystack
Singh has been studying virology and DNA genome replication for nearly 30 years. He said the homology, or structure, of the mpox virus, is very similar to the vaccinia virus, which has been used as a vaccine to treat smallpox. This enabled Singh and his collaborators to create an accurate, 3D computer model of the mpox virus proteins and identify where the specific mutations are located and their functions in recently contributing to the virus becoming so infectious.
"Our focus is on looking at the specific genes involved in copying the virus genome, and mpox is a huge virus with approximately 200,000 DNA bases in the genome," Singh said. "The DNA genome for mpox is converted into nearly 200 proteins, so it comes with all the 'armor' it needs to replicate, divide and continue to infect others. Viruses will make billions of copies of themselves, and only the fittest will survive, as the mutations help them adapt and spread."
Kannan and Kandasamy examined five specific proteins while analyzing the mpox virus strains: DNA polymerase, DNA helicase, bridging protein A22R, DNA glycosylase, and G9R.
"When they sent me the data, I saw that the mutations were occurring at critical points impacting DNA genome binding, as well as where drugs and vaccine-induced antibodies are supposed to bind," Singh said. "These factors are surely contributing to the virus' increased infectivity. This work is important because the first step toward solving a problem is identifying where the problem is specifically occurring in the first place, and it is a team effort."
The Evolution of Viruses
Researchers continue questioning how the mpox virus has evolved. The efficacy of current CDC-approved drugs to treat mpox has been suboptimal, likely because they were originally developed to treat HIV and herpes but have since received emergency use authorization in an attempt to control the recent mpox outbreak.
"One hypothesis was when patients were being treated for HIV and herpes with these drugs, they may have also been infected with mpox without knowing, and the mpox virus got smarter and mutated to evade the drugs," Singh said. "Another hypothesis is that the mpox virus may be hijacking proteins in our bodies and using them to become more infectious and pathogenic."
Singh and Kannan have collaborated since the COVID-19 pandemic began in 2020, identifying the specific mutations causing COVID-19 variants, including Delta and Omicron. The United Nations recently recognized Kannan for supporting their 'Sustainable Development Goals,' which help tackle the world's greatest challenges.
"I could not have done this research without my team members, and our efforts have helped scientists and drug developers assist with these virus outbreaks, so it is rewarding to be a part of it," Singh said.
"Mutations in the mpox virus replication complex: Potential contributing factors to the 2022 outbreak" was recently published in Journal of Autoimmunity. Co-authors on the study include Shrikesh Sachdev, Athreya Reddy, Shree Lekha Kandasamy, Siddappa Byrareddy, Saathvik Kannan, and Christian Lorson.
Insights, Analysis, and Developments
Editorial Note: As we grapple with yet another viral threat that's proving remarkably adept at adaptation, this study serves as a stark reminder of nature's relentless innovation in the face of medical interventions—much like how smallpox vaccines once seemed invincible until variants emerged. It underscores the urgent need for agile, mutation-aware drug design and global surveillance systems, not just to contain mpox but to preempt similar escalations in other diseases, ensuring that scientific foresight keeps pace with microbial cunning for the sake of public health resilience worldwide - Disabled World (DW).Attribution/Source(s): This peer reviewed publication was selected for publishing by the editors of Disabled World (DW) due to its relevance to the disability community. Originally authored by University of Missouri-Columbia and published on 2022/11/05, this content may have been edited for style, clarity, or brevity.