La climatisation ne provoque pas directement un rhume ou une grippe. En revanche, elle peut créer des conditions favorables au développement d’infections. On démêle le vrai du faux.
Researchers at Washington University School of Medicine in St. Louis have made a groundbreaking discovery that could revolutionize the prevention of diarrheal diseases caused by enterotoxigenic Escherichia coli (ETEC) and Shigella. These two bacterial pathogens are responsible for hundreds of millions of infections annually and are leading causes of diarrheal mortality worldwide, particularly among young children. Despite decades of efforts, vaccine development has encountered significant obstacles, primarily due to the extensive strain variability that hampers the identification of universal vaccine targets.
In a recent study published in the Proceedings of the National Academy of Sciences, the WashU team, collaborating with scientists at the University of Missouri and the International Centre for Diarrhoeal Disease Research in Bangladesh, identified a shared vulnerability within these pathogens that could open the door for a combined vaccine platform. This innovative approach hinges on targeting homologous enzymes that these bacteria use to degrade the mucus lining in the human gut, a critical step in establishing infection.
For bacterial pathogens like ETEC and Shigella to cause illness, they first need to overcome the intestinal mucus barrier. This thick layer of mucus serves as a physical and biochemical shield protecting the gut epithelium and regulating the microenvironment by keeping pathogenic entities at bay while preserving the beneficial microbiota. The ability to breach this barrier is a hallmark of pathogenicity, allowing bacteria to access the underlying tissues and deploy additional virulence factors, including enterotoxins that induce diarrhea.
The study’s focal point is a family of mucin-degrading enzymes that facilitate this breaching process. The researchers detail three closely related enzymes—EatA, SepA, and Pic—that are expressed by ETEC, Shigella, and other diarrheal pathogens. EatA, an acronym for “eat away,” is produced by ETEC and was previously identified by Fleckenstein’s laboratory as a critical mucinase targeting the primary structural protein within mucus. SepA and Pic, related enzymes produced by Shigella and some other bacteria, perform analogous roles. Their enzymatic activity effectively dismantles the mucosal barrier, clearing a path for bacterial invasion.
Intriguingly, the antibodies that the team isolated from individuals infected with ETEC or experimentally exposed to the bacteria displayed a functional cross-reactivity. The antibodies not only neutralized EatA but also inhibited SepA and Pic, indicating a conserved epitope region among these mucinases. This neutralization prevents the enzymes from degrading intestinal mucus, thereby blocking the pathogens’ entry into host tissues. The concept of a single antibody interfering with multiple bacterial targets underscores a significant breakthrough in vaccine strategy.
To unravel the structural mechanics behind this immune neutralization, the researchers leveraged cryo-electron microscopy—a state-of-the-art imaging method that preserves biomolecules in near-native states by flash-freezing samples. This technique enabled detailed visualization at atomic resolution, revealing the precise binding site of the neutralizing antibodies. Remarkably, the site of interaction was a structurally conserved region across EatA, SepA, and Pic, providing a rational basis for the design of vaccine antigens that elicit broadly neutralizing antibodies.
“The identification of this shared Achilles’ heel among diverse diarrhea-causing bacteria signifies a paradigm shift in vaccine development,” explains James M. Fleckenstein, MD, co-senior author of the study and professor of medicine at WashU. “It suggests we can target a common mechanism of gut colonization rather than chasing highly variable surface molecules, which has been the stumbling block in the field for so long.”
Further bolstering the translational potential of these findings, epidemiological data from children in Dhaka, Bangladesh, indicate that naturally acquired antibodies against EatA correlate with protection from diarrheal illness. This natural immunity validates EatA as a viable immunological target and encourages the pursuit of vaccines that induce similar protective responses.
The implications extend beyond the developing world, as enterotoxigenic E. coli has been implicated in recent foodborne outbreaks in industrialized countries such as the United States. The difficulty in distinguishing pathogenic ETEC from non-pathogenic strains in clinical settings further complicates diagnosis and containment. Moreover, reliance on antibiotics to treat infections caused by these bacteria accelerates the evolution of antibiotic resistance, posing a global public health threat.
Zachary Berndsen, PhD, assistant professor of biochemistry at the University of Missouri and co-senior author, emphasizes the rational approach to vaccine design enabled by these insights. “By pinpointing enzyme domains targeted by neutralizing antibodies, we provide a template for crafting precise immunogens that can stimulate protective immunity across multiple pathogens. This can streamline the production of vaccines that are both effective and broad-spectrum,” Berndsen says.
Development of such a vaccine could not only reduce the global burden of diarrheal diseases but also mitigate the spread of antibiotic resistance by decreasing the frequency of bacterial infections requiring treatment. Additionally, preserving the gut microbiota through targeted disruption of pathogenic mechanisms may alleviate some adverse consequences associated with broad-spectrum antibiotic use.
Going forward, the research team is focused on translating their molecular discoveries into practical vaccine candidates. This involves preclinical testing of immunogens incorporating the conserved epitopes identified, assessing their immunogenicity and protective efficacy in animal models, and progressing toward human clinical trials.
“In our ongoing battle with enteric pathogens that have coevolved with humans for millennia, blocking the enzymatic opening of the mucus gate represents a promising strategy,” Fleckenstein concludes. “If successful, this vaccine would preempt infection at its earliest and most vulnerable stage, changing the trajectory of diarrheal disease worldwide.”
The study was supported by grants from the National Institute of Allergy and Infectious Diseases and the Department of Veterans Affairs. The multidisciplinary collaboration brings together expertise in infectious diseases, structural biology, immunology, and clinical research, underscoring the necessity of integrated approaches to tackle complex global health challenges.
Subject of Research: Human tissue samples
Article Title: Human enterotoxigenic Escherichia coli (ETEC) infections elicit antibodies that broadly neutralize mucinases of pathogenic Escherichia coli and Shigella
News Publication Date: 15-Jun-2026
References:
Buckley DP, Akhtar M, Thapa M, Schmitz A, Turner J, Vickers TJ, Khatoon N, Kaisar MH, Coggin JA, Ganguli D, Sheikh A, Laird RM, Poly F, Porter CK, Ruiz-Perez F, Miller MJ, Chowdhury F, Bhuiyan TR, Qadri F, Trillo-Muyo S, Dolan B, van der Post S, Ellebedy A, Berndsen ZT, Fleckenstein JM. Human enterotoxigenic Escherichia coli (ETEC) infections elicit antibodies that broadly neutralize mucinases of pathogenic Escherichia coli and Shigella. PNAS. June 15, 2026.
University of California, Irvine Innovates Therapeutic Vaccine Strategy to Combat Recurrent Genital Herpes
In a groundbreaking development that could transform the management of genital herpes, UC Irvine immunologist Lbachir BenMohamed has secured nearly $4 million in funding from the National Institutes of Health to advance a novel therapeutic vaccine approach. This ambitious five-year project aims to tackle recurrent genital herpes caused by herpes simplex virus type 2 (HSV-2), a persistent viral infection that affects over 60 million Americans and more than half a billion individuals globally. Despite extensive research efforts historically, no approved therapeutic vaccine exists to date, leaving millions vulnerable to recurrent outbreaks and transmission.
BenMohamed’s research focuses on a next-generation vaccine strategy termed “Prime/Pull/Keep,” designed to establish a robust, localized immune defense precisely at the mucosal sites where HSV-2 resides and reactivates. Conventional vaccines predominantly elicit circulating antibodies, which are insufficient to control HSV-2’s latent reservoirs in the nerve ganglia and mucosal tissues. This innovative approach instead targets tissue-resident memory T cells (TRM), a specialized subset of immune cells critically positioned at the barrier sites to provide immediate defense against viral reactivation.
The Prime/Pull/Keep methodology encompasses a three-step immunization process: initial priming of protective T cells via vaccination, mobilization of these cells to the infected tissue through chemokine signals (pull), and sustained retention and functional maintenance at the site of infection (keep). Together, these steps ensure a sustained population of antiviral T cells, capable of rapid detection and elimination of reactivated virus, potentially curbing recurrent disease manifestations and viral shedding.
Previous investigations by BenMohamed’s team have demonstrated promising results with mRNA-based therapeutic vaccines in preclinical models. These candidates were effective in reducing clinical signs of recurrent genital herpes and enhancing the recruitment of protective T cells within genital mucosal tissues. Additionally, exploring immune-signaling molecules such as chemokines has validated the feasibility of attracting and retaining TRM populations, thereby improving local immune surveillance and long-term antiviral immunity.
The current NIH-funded project intends to rigorously evaluate the safety profile and immunogenic potential of various Prime/Pull/Keep vaccine candidates in preclinical animal models, examining how augmenting the quantity, quality, and durability of TRM cells correlates with protection from HSV-2 reactivation. This represents a critical translational step toward bridging laboratory research and clinical trials, responding to NIH’s strategic priority to develop novel therapeutic interventions for genital herpes.
BenMohamed articulates the significance of this research succinctly: “People living with recurrent genital herpes have long awaited effective therapeutic vaccines. Our innovative immune-based approach not only amplifies protective T cells but directs and maintains them where the virus hides. This could revolutionize prevention strategies for millions affected worldwide.” The team’s vision is to develop a vaccine capable of reducing recurrent outbreaks and viral transmission, substantially improving quality of life for patients.
HSV-2 represents a formidable pathogen due to its ability to establish lifelong latent infection in sensory neurons, periodically reactivating to cause painful genital lesions and facilitating onward transmission. Existing antiviral therapies focus on suppressing viral replication but do not eliminate reservoirs or prevent recurrence. The targeted boosting of tissue-resident immune memory represents a paradigm shift in immunotherapy, promising durable tissue-specific immunity where it is needed most.
The Prime/Pull/Keep vaccination strategy could also circumvent issues faced by traditional systemic vaccines, which often fail to generate sufficient mucosal immunity or induce long-lasting memory T cell populations within genital tissues. By tailoring antigen delivery and immune modulation, this approach aims to enhance the local microenvironment and foster a self-renewing population of sentinel T cells poised to respond immediately to viral reactivation.
As the project advances through preclinical stages, rigorous assessment of immune correlates of protection will inform optimization of vaccine formulations, dosing schedules, and adjuvant combinations. Understanding the mechanisms underpinning TRM cell maintenance and functionality remains an active area of investigation critical to maximizing therapeutic efficacy and durability.
The successful identification of an optimal Prime/Pull/Keep candidate would pave the way for human clinical trials, marking a historic milestone in the fight against genital herpes. Such a vaccine holds the promise not only to alleviate recurrent symptoms but also to significantly curtail viral shedding, thereby decreasing transmission rates and public health burden.
Beyond genital herpes, the conceptual framework underlying Prime/Pull/Keep may inspire novel immunotherapeutic strategies for other persistent viral infections and chronic diseases where localized immune memory is pivotal. Collaborative efforts among immunologists, virologists, and clinical scientists will be essential to translate these findings into effective interventions.
With UC Irvine’s robust infrastructure, cutting-edge facilities, and interdisciplinary expertise, BenMohamed’s laboratory is well-positioned to spearhead this transformative endeavor. The $3.93 million NIH R01 grant underscores the scientific community’s confidence in this pioneering approach and its potential to redefine therapeutic vaccine development for chronic viral infections.
In conclusion, the UC Irvine-led Prime/Pull/Keep vaccine project represents a beacon of hope for millions plagued by recurrent genital herpes, offering a sophisticated and strategic means to harness the immune system’s power at the precise sites of viral latency and reactivation. As research progresses, the scientific world eagerly anticipates the realization of a durable, tissue-targeted therapeutic vaccine capable of changing the landscape of HSV-2 management and prevention.
Subject of Research: Development of a novel therapeutic vaccine to prevent recurrent genital herpes by targeting tissue-resident memory T cells
Web References:
– University of California, Irvine: www.uci.edu
– UC Irvine News: news.uci.edu
– NIH Media Resources: https://news.uci.edu/media-resources/
Login
