Jyothi N Purushotham, PhD, and Holly L Lutz, PhD, call for integrated immunological and ecological strategies to counter fast-evolving viral threats.
Jyothi N Purushotham, PhD
Image credits: LinkedIn
Holly L Lutz, PhD
Image credits: LinkedIn
According to a new article published in Immunity, the disruption of natural ecosystems from climate change and human activity is increasing the risk of zoonotic virus spillover. Over the past 20 years, repeated zoonotic outbreaks have exposed limitations in predicting epidemic trajectories and deploying effective responses. RNA viruses pose a particular challenge due to their high mutation rates and ability to evade immune defenses.
The study emphasizes the importance of understanding how antibody-mediated immunity interacts with viral evolution to improve outbreak prediction and control. Despite advances, major knowledge gaps remain in how viruses emerge, spread, and persist in human populations. Addressing these gaps is essential for strengthening surveillance systems and guiding public health strategies.
The investigators call for an integrated approach across immunology, virology, and ecology to identify drivers of viral emergence. Research priorities include immune memory, host-pathogen dynamics, and the impact of ecological change on disease transmission.
We spoke to investigators Jyothi N Purushotham, PhD, postdoctoral research associate and K12 clinical scholar at The Scripps Research Institute, and Holly L Lutz, PhD, associate curator of mammals at the Denver Museum of Nature & Science, about their recent perspective article in Immunity, which examines how immune responses shape the emergence and persistence of zoonotic viruses. The discussion covered antibody-virus dynamics, tools for outbreak prediction, and recent immunological advances that could inform future therapies and vaccines.
Purushotham and Lutz: "Human activities that disrupt natural ecosystems are increasing the likelihood that viruses spill over from wildlife into human populations, underscoring the need for continued surveillance and adaptable public health strategies," the authors stated. "As we continue to encounter these emerging zoonotic viruses, proactively considering the interplay between antibody-mediated immunity and viral evolution will be essential for effectively mitigating their spread and impact on our communities."
They explained that when a novel virus first emerges, it encounters populations with little to no prior immunity. Early on, viral evolution is driven primarily by the need to enhance replication and transmission in human hosts—an evolutionary trajectory observed with early SARS-CoV-2 mutations like D614G. Over time, as population-level immunity builds through infection or vaccination, viruses face increasing selective pressure from neutralizing antibodies, which drives mutations that enable immune escape and result in antigenic drift. This has been well documented in both influenza viruses and SARS-CoV-2.
Purushotham and Lutz: "This arms race between viral evolution and immunity ultimately shapes how viruses spread, persist, and become endemic," they said. Factors such as immune imprinting, waning antibody levels, and memory B cell maturation all influence whether immunity constrains or promotes viral evolution. "Going forward, how exactly these antibody-virus dynamics evolve will depend heavily on the strength, durability, and breadth of antibody responses within our communities."
They emphasized that ongoing genomic and immunological surveillance, longitudinal studies of antibody and B cell dynamics, and vaccine designs that consider both viral and host immune factors are essential. "Ultimately, our goal is to establish broadly protective, durable, and adaptable immunity that can keep pace with the evolution of these emerging viruses."
Purushotham and Lutz: "That’s an important question, especially as we continue to see how quickly RNA viruses can adapt and spread," they said. One of the most effective starting points, they argue, is strengthening global surveillance—not just in humans, but in animal reservoirs where spillovers originate.
Among the most promising tools is wastewater surveillance, which offers early detection of viral emergence and real-time tracking of transmission and evolution. It has proven useful during the COVID-19 pandemic and is now being expanded to monitor additional viruses, including influenza, measles, hepatitis A, and Mpox.
Equally important are rapid diagnostics and pan-viral sequencing platforms that enable early detection of spillover events. However, they noted, "The effectiveness of all of these tools hinges on them being readily available and deployable in outbreak-prone regions, which are often resource-limited."
Alongside surveillance, the researchers emphasized the importance of immunological monitoring, including seroepidemiology, sentinel cohort studies, and expanded research capacity in vulnerable areas. "Understanding the immune landscape—who has immunity, how long it lasts, and how it varies—is critical for designing interventions."
Disruption of ecosystems from human activity and climate change is increasing the frequency of zoonotic virus spillover.
Antibody-mediated immunity drives viral evolution over time, making it critical to understand immune-virus dynamics for effective intervention.
Global surveillance, vaccine adaptability, and equitable access are essential to preparing for and managing future outbreaks.
On the prevention side, they cited adaptable vaccine platforms like mRNA and viral-vectored vaccines as key. "These can be swiftly updated as new variants emerge," they noted. Ensuring global access and equitable distribution is critical to limiting virus evolution and reducing impact.
Finally, they stressed that data integration with ecological modeling and strong international coordination are fundamental. "Sharing data transparently and responding collaboratively across sectors will be key to staying ahead of the next zoonotic threat."
Purushotham and Lutz: "In recent years, we have seen major advances in immunology that are reshaping our strategies for tackling emerging and evolving viral threats," they said. One of the most promising areas is vaccine design. Advances in structural biology, protein engineering, and AI now allow scientists to identify conserved viral regions less prone to mutation, enabling the development of immunogens that offer broader and more durable protection.
Another promising approach is broad immune priming—exposing the immune system to multiple antigenic variants to generate cross-reactive antibody responses. These can be delivered using multivalent or cocktail vaccines, or via sequential immunizations. "By diversifying these early immune responses, we can potentially overcome limitations associated with immune imprinting," they explained.
On the therapeutic front, recent progress in antiviral drug development, including COVID-19 treatments like molnupiravir and Paxlovid, has demonstrated the value of targeting highly conserved viral proteins. The authors stressed the importance of accelerated drug discovery platforms and the development of broad-spectrum antivirals that target shared viral features across families.
They also pointed to advancements in monoclonal antibody therapies, particularly during COVID-19, which saw rapid development of potent antibodies against the spike protein. However, they caution that this strategy faces challenges related to cost, limited breadth, and potential to drive immune escape. "Moving forward, we need to focus on engineering broadly neutralizing antibodies and using them in smarter combinations."
"Collectively, these advances—when combined with better surveillance and global coordination—give us a much stronger foundation to respond to future outbreaks," they concluded. "But we must remain mindful of the evolutionary pressures we are working against. Viruses adapt quickly, and our interventions need to stay one step ahead."
