As an invisible killer lurking inside the vast majority of humans, the Epstein-Barr virus (EBV) has perplexed the global medical community for decades. Over 95% of Chinese people carry EBV; it lies dormant without symptoms during early childhood, yet easily triggers illnesses in adolescence and persists in the human body for a lifetime. Each year, it causes hundreds of thousands of malignant tumors and millions of infectious and autoimmune diseases, and it is the primary culprit behind nasopharyngeal carcinoma, a malignancy prevalent in Guangdong Province. For a long time, global R&D of EBV vaccines has repeatedly hit roadblocks, with no approved products reaching the market to date.

On the morning of August 22, at the themed event on high-quality development of innovative biomedical technologies held during the 2026 Guangzhou Medical Expo, Academician Zeng Musheng, Member of the Chinese Academy of Sciences and Deputy Director of Sun Yat-sen University Cancer Center, unveiled that his team’s landmark scientific achievements are poised for industrial translation. Multiple preventive and therapeutic vaccines as well as targeted drugs have entered critical translation stages. Meanwhile, the team has officially launched initiatives to explore overseas markets, signaling that China’s self-developed EBV prevention and treatment products will soon be launched, expected to put an end to the lack of effective interventions for EBV-associated diseases.

Hidden Dangers Far Beyond Imagination — EBV Is Linked to Numerous Diseases Beyond Nasopharyngeal Carcinoma

Unlike well-known oncogenic viruses such as those causing liver and cervical cancer, EBV is the first tumor-associated virus discovered in humans and one of the most widespread pathogens linked to the broadest spectrum of diseases, yet it has long been overlooked by the general public. Epidemiological data shows that over 95% of Chinese individuals are infected with EBV, most contracting the virus during early childhood without obvious symptoms. The virus then establishes lifelong latency in the human body and can be transmitted orally every day.

Its high infection rate and lifelong persistence impose an immense global disease burden. Statistically, EBV causes 300,000 new malignant tumor cases worldwide each year, including 129,000 nasopharyngeal carcinoma cases, 84,000 gastric cancer cases, 28,600 Hodgkin’s lymphoma cases, and thousands of Burkitt’s lymphoma cases. It constitutes the core pathogenic driver of nasopharyngeal carcinoma endemic to South China.

Beyond malignant tumors, EBV triggers 1.5 million infectious illnesses annually, predominantly infectious mononucleosis, and is associated with over 30 million autoimmune disorders including systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, and chronic fatigue syndrome. Recent research has confirmed that the activation pathways of numerous autoimmune diseases are closely tied to latent EBV infection and abnormal viral reactivation. Based on this pivotal discovery, Zeng Musheng’s team has secured funding for a major program of the National Natural Science Foundation of China to specifically investigate the core mechanisms through which EBV induces childhood lupus and lupus nephritis.

Decades of Failed Global R&D — Chinese Team Uncovers Root Causes of EBV Vaccine Setbacks

Global scientists have dedicated decades to EBV vaccine research. The late Academician Zeng Yi, a distinguished Chinese virologist, pioneered clinical research on EBV vaccines, yet all candidate vaccines developed over the past decades have failed to meet marketing approval criteria, with none successfully commercialized.

“Past failures stem fundamentally from gaps in basic scientific research,” Academician Zeng Musheng pinpointed the industry bottleneck during his academic presentation. Three critical obstacles have hampered global vaccine development for half a century:

1. For 50 years, the core receptor mechanism enabling EBV to infect human epithelial cells remained unsolved, lacking efficient in vitro research models.

2. Conventional theories held that EBV employs two entirely separate receptor systems to infect B cells and epithelial cells, forcing segmented R&D that cannot achieve full-spectrum viral blockade.

3. The pathogenic functions and immunogenicity of more than a dozen viral surface glycoproteins were poorly characterized, making it impossible to identify precise vaccine targets.

Furthermore, EBV naturally infects only humans and marmosets, and mature animal infection models were long unavailable. This severely restricted in vivo efficacy verification and drug screening, further stalling global research progress.

Landmark Research Published in Nature — Global First Discovery of the Universal EBV Infection Receptor

Tackling this half-century-long industry-wide challenge, Zeng Musheng’s team conducted in-depth mechanistic basic research and delivered multiple disruptive original breakthroughs, with several findings published in top international journals, completely reshaping the theoretical framework of EBV infection.

The team innovatively proposed the hypothesis of an “EBV susceptibility window in nasopharyngeal epithelial precancerous lesions” and established the world’s first efficient in vitro organoid model for EBV infection of precancerous epithelial tissue. This overcame the technical bottleneck of low EBV epithelial infection efficiency that had blocked in vitro research for decades and filled a fundamental disciplinary gap.

The most transformative breakthrough is the world’s first identification of the universal EBV infection receptor R9AP, formally published in Nature in June 2025. Research confirms R9AP is the sole key receptor mediating EBV entry into both epithelial cells and B cells, overturning the decades-old global consensus of the “dual receptor system for two cell types”. Simply put, R9AP acts as a universal gateway that EBV uses to invade the two primary target human cell types; blocking this single target can fully shut down both viral infection pathways and curb infection at its source.

Building on this finding, the team further elucidated the complete mechanistic cascade: R9AP coordinates with specific co-receptors including EphA2 and HLA class II molecules to sequentially mediate viral adhesion, cell fusion and cellular entry. This established an entirely new theory of sequential multi-receptor synergy driving cross-cell EBV infection, delivering the core scientific foundation for precise vaccine and targeted drug development. Meanwhile, the team identified the cross-species restriction receptor DSC2, resolving the longstanding obstacle of EBV animal models and providing mature experimental carriers for vaccine efficacy testing and drug screening.

Dual-track Vaccine System Launched — Full Coverage of Healthy Populations and Infected Individuals

Guided by the novel infection mechanism theory, Zeng Musheng’s team broke free from conventional R&D logic and built a dual preventive + therapeutic EBV vaccine pipeline, covering uninfected healthy individuals, high-risk infected populations, and tumor patients — filling a global industry gap.

For uninfected children, the team developed the world’s first EBV prophylactic vaccine, precisely targeting key immunogenic viral glycoproteins gH/gL and gB. It efficiently induces robust conserved neutralizing antibodies in the human body to preempt viral infection and drastically reduce the risk of nasopharyngeal carcinoma and other EBV-associated malignancies. “This vaccine has been fully licensed to a leading domestic listed vaccine enterprise and has entered industrial translation,” Zeng Musheng disclosed.

For the over 95% of Chinese population already infected, and the millions of new EBV-related tumor cases projected over the coming decades, the team overcame technical limitations to create a chimeric nanoparticle vaccine (published in Advanced Materials, October 2025). This innovative vaccine displays multiple core EBV glycoproteins chimerically on nanoparticle surfaces, perfectly mimicking native viral structure. It efficiently accumulates in lymph nodes, activates robust systemic immune responses, and generates broad-spectrum, potent neutralizing antibodies.

Notably, this nanoparticle vaccine exhibits broad cross-species protective activity. Zeng stated that the vaccine not only blocks human EBV infection but also effectively suppresses diverse herpesviruses infecting mice, cattle, horses and primates, outperforming traditional vaccines in broad-spectrum protection. In parallel, the team developed an mRNA therapeutic vaccine targeting latent EBV proteins, which potently activates human T-cell anti-tumor immunity. It has completed preclinical validation and is currently applying for clinical trial authorization.

Multi-drug Pipeline Delivers Parallel Breakthroughs — Full-cycle Intervention for Infection and Malignancy

Beyond its vaccine portfolio, Zeng Musheng’s team established a full-chain EBV drug R&D pipeline covering acute infection intervention, tumor treatment and post-operative complication management.

“We built the world’s largest fully human phage display antibody library for nasopharyngeal carcinoma, sourced from samples of 100 nasopharyngeal carcinoma patients, and successfully screened and characterized over 50 fully human EBV monoclonal antibodies,” Zeng explained. The dual-target neutralizing antibody drug developed from these core antibodies achieves ultra-high nanogram-level neutralization efficiency, outperforming all global comparable EBV antibody products in potency with excellent formulation stability. It is specially designed to prevent EBV infection in organ and hematopoietic stem cell transplant recipients and avert post-transplant lymphoproliferative disorders.

In addition, the team’s antibody-drug conjugate (ADC) demonstrated curative efficacy in animal studies: it suppresses over 90% of B-cell lymphoma lesions and completely eradicates NKT lymphoma tumors to achieve tumor remission. Small-molecule targeted therapeutics and novel nucleic acid immunotherapies are also under concurrent development, forming a complete EBV prevention and treatment ecosystem consisting of prophylactic vaccines, neutralizing blocking antibodies and therapeutic drugs.

Indigenous Chinese Cutting-edge Research Goes Global — Vaccine Poised to Enter Clinical Trials

After over two decades of dedicated research, Zeng Musheng’s team has fully broken Western technological monopolies in EBV prevention and treatment, achieving a transformative leap from following global leaders to taking the international lead. Multiple achievements are now counting down to industrialization. Addressing executives from biopharmaceutical enterprises at the conference, Zeng Musheng remarked: “Domestically, our team has forged deep partnerships with leading local manufacturers to accelerate domestic production and clinical deployment of vaccines and drugs, and we welcome collaboration with more enterprises.”

Reporters learned that the prophylactic anti-EBV vaccine is the most advanced asset, expected to file an IND (Investigational New Drug) application next year. Therapeutic vaccines and ADC drug pipelines remain in the financing stage, requiring strengthened industrial collaboration and policy support for rapid rollout.

The team’s groundbreaking research has attracted top global pharmaceutical giants. A dedicated headquarters team from one of the world’s leading biopharma firms recently traveled to Guangzhou for in-depth exchanges to explore global cooperation frameworks for the EBV vaccine. Zeng Musheng explicitly confirmed that the team will actively pursue overseas market expansion, leveraging its original proprietary core technologies to bring China-developed EBV vaccines and innovative drugs to patients worldwide.

Industry insiders commented that Zeng Musheng’s suite of breakthroughs not only resolves century-old scientific puzzles regarding EBV oncogenesis but also establishes the world’s first mature full-spectrum EBV prevention and treatment technology system. With the launch of the prophylactic vaccine, entry of therapeutic vaccines into clinical trials, and successive translation of multiple specialty drugs, the persistent public health challenges posed by nasopharyngeal carcinoma, EBV-associated lymphomas and autoimmune diseases may be fully resolved in the future, truly consigning EBV-related illnesses to history.

Source: Yangcheng Evening News