I’m thrilled to sit down with Ivan Kairatov, a biopharma expert with extensive experience in research and development, and a deep understanding of technological innovation in the industry. Today, we’re diving into the groundbreaking work on novel monoclonal antibodies for mpox, a viral disease that has raised global concern in recent years. Ivan will share insights on the science behind these antibodies, the challenges of treating orthopoxviruses, and the potential impact of this research on public health. Our conversation explores the nature of mpox, the innovative approaches to combating it, and the journey from lab discoveries to real-world applications.
Can you give us a broad picture of what mpox is and why it’s become such a pressing issue in recent times?
Mpox is a viral disease caused by an orthopoxvirus, related to the virus that causes smallpox. It typically spreads through close contact with an infected person, often via skin-to-skin contact, respiratory droplets, or contaminated objects. Symptoms include a painful rash, fever, and swollen lymph nodes, and in severe cases, it can lead to significant illness or scarring. It’s become a major concern since a global outbreak began in 2022, prompting the World Health Organization to declare it a public health emergency of international concern on multiple occasions. The lack of effective, approved treatments has only heightened the urgency to address this disease, especially as cases continue to emerge worldwide.
What drove your interest in developing new treatments for mpox, and were there specific gaps in existing options that pushed you in this direction?
Our motivation stemmed from the clear unmet need for effective therapies against mpox and other orthopoxviruses. While there are vaccines for related viruses like smallpox, therapeutic options for active mpox infections are limited, and recent clinical trials for leading drug candidates have been disappointing. We saw an opportunity to leverage our expertise in virology and immunology to fill this gap. The urgency of the ongoing outbreak, combined with the potential severity of the disease, made it a priority for us to explore innovative solutions like monoclonal antibodies that could offer both prevention and treatment.
How did earlier discoveries about the A35 protein shape the focus of your recent research on mpox?
Our prior work in 2023 was pivotal. We found that human antibodies targeting the A35 protein—a key component of the mpox virus—were significantly elevated in individuals who had recovered from the infection compared to those who had only been vaccinated against smallpox. This suggested that A35-specific antibodies played a critical role in the body’s natural defense against the virus. Building on that, we hypothesized that isolating and developing antibodies targeting A35 could lead to a highly effective treatment. This earlier insight gave us a clear starting point and a strong rationale for focusing on this protein in our latest study.
For those unfamiliar with the term, could you explain what monoclonal antibodies are and how they help fight mpox?
Absolutely. Monoclonal antibodies are lab-made proteins designed to mimic the immune system’s ability to fight off pathogens. They’re engineered to target specific parts of a virus—in this case, the mpox virus—and neutralize it. For mpox, the antibodies we’ve developed bind to the A35 protein on the virus’s surface, which prevents the virus from spreading between cells. Think of them as highly precise tools that lock onto the virus and stop it in its tracks, helping the body clear the infection before it causes severe damage.
What makes the three antibodies you’ve discovered stand out compared to other potential treatments?
What’s unique about these three antibodies is their potency and specificity. They target a very specific region of the A35 protein that’s critical for the virus’s ability to spread. In lab tests, they completely blocked viral spread, and in animal models, they protected rodents from severe disease and death. Additionally, we found that people who’ve recovered from mpox naturally produce high levels of similar antibodies, which correlates with milder symptoms. This suggests our antibodies are tapping into a naturally effective immune response, which gives us confidence in their potential as a therapeutic option.
Your study showed impressive results in rodents. Can you walk us through how you tested these antibodies and what the outcomes were?
We conducted rigorous experiments using rodent models infected with mpox. After administering the antibodies, we monitored the animals for signs of disease progression, viral spread, and overall survival. The results were striking—the antibodies not only prevented severe symptoms but also completely protected the rodents from death, even when exposed to high viral loads. These tests involved both preventative and therapeutic approaches, meaning we gave the antibodies before and after infection to see their full range of effectiveness. It was a strong indication of their protective power in a controlled setting.
How optimistic are you that these findings in rodents could eventually apply to humans?
I’m cautiously optimistic. While rodent models are a critical step in understanding how a treatment might work, there are always differences between animal and human biology that we need to account for. That said, the fact that these antibodies target a mechanism conserved across orthopoxviruses, and that humans who’ve had mpox already produce similar antibodies, gives us a strong foundation to build on. The next step is to move into advanced preclinical studies and eventually human clinical trials to confirm safety, efficacy, and how the antibodies behave in the human body.
You’ve noted that a conserved region of the virus is targeted by these antibodies. Can you explain what that means and why it’s significant?
A conserved region refers to a part of the virus’s structure that remains very similar across different strains or even related viruses, like those in the orthopoxvirus family. It’s a stable target because it doesn’t change much through mutations, which viruses often do to evade treatments or vaccines. Targeting a conserved region, like the specific epitope on the A35 protein, is significant because it increases the likelihood that our antibodies will work against various mpox strains and potentially other poxviruses. It’s like finding a universal weak spot that the virus can’t easily escape from, making the treatment more robust and versatile.
Since this research is still in early development, what are the key hurdles or steps ahead before these antibodies could become a viable treatment for humans?
We’re at an exciting but early stage. The next steps involve advanced preclinical testing to evaluate safety, dosage, and how the antibodies distribute and persist in the body. We’ll need to ensure there are no unexpected side effects and that the antibodies remain effective in more complex biological systems. After that, we’ll move into human clinical trials, which are crucial for proving efficacy and safety in people. This process takes time, often several years, and requires collaboration with regulatory bodies to meet strict standards. We’re also exploring how to scale up production if the antibodies prove successful.
Looking ahead, what is your forecast for the future of mpox treatments and the role of monoclonal antibodies in managing this disease?
I believe monoclonal antibodies have immense potential to transform how we manage mpox and other orthopoxvirus infections. If our research progresses as hoped, we could see these antibodies becoming a cornerstone of both prevention and treatment, especially for high-risk populations or during outbreaks. Beyond that, the insights we’re gaining into the immune response to mpox could inform broader strategies for tackling related viruses. While challenges remain, I’m hopeful that within the next decade, we’ll have more effective tools to control mpox, reducing its impact on global health significantly.
