Zejiang Difference Biological Technology announced that its proprietary nasal spray influenza attenuated live vaccine, DIFF-flu, has recently received clinical trial approval as a Class 1.2 innovative vaccine from China's National Medical Products Administration (NMPA).

As the first domestically self-developed nasal spray influenza vaccine in China to advance into clinical trial, DIFF-flu leverages a pioneering M2 gene–modified attenuation technology, protected by multiple international invention patents. This achievement underscores DIFF Biotech's leading capabilities in respiratory infectious disease prevention and establishes an important foundation for future industrialisation.

Dr Jiasheng Song, Chief Executive Officer, DIFF Biotech, commented, "DIFF-flu's clinical approval marks a major milestone for DIFF Biotech and a meaningful achievement for independent innovation in respiratory infectious disease prevention. As a next-generation attenuation platform, DIFF-flu is designed to achieve an optimal balance between immunogenicity and safety—an advance that holds significant potential for improving influenza protection. We believe this progress will help expand access to safer, more effective influenza prevention, particularly for older adults and other vulnerable populations. DIFF Biotech will continue to drive next-generation vaccine innovation to strengthen public health and contribute to global biomedical progress."

DIFF-flu is developed using an innovative M2 gene–modification strategy that produces a replication-restricted vaccine strain. This approach achieves a deliberate balance between robust attenuation and strong immunogenicity—generating a potent immune response while maintaining an exceptional safety profile. In essence, the technology places a "safety harness" on the virus to prevent uncontrolled replication.

Existing nasal spray influenza vaccines on the market rely on cold-adapted attenuation, allowing the vaccine virus to replicate efficiently only at lower temperatures such as those in the nasal cavity, but limiting replication in the warmer lower respiratory system and lungs. Because these strains can still replicate in nasal mucosa and cause mild viral shedding, these are generally not recommended for older adults or immune-compromised individuals.

Pre-clinical data indicate that DIFF-flu offers a differentiated safety profile, with negligible viral shedding and significantly reduced viral loads in respiratory tissues, suggesting the potential to extend nasal spray vaccine eligibility to older adults and other underserved groups.

Notably, pre-clinical data show that DIFF-flu confers 100 percent protection against epidemic strains circulating over 50 years ago, while also eliciting strong immunity against contemporary variants.

The global influenza vaccine market is undergoing a period of structural evolution. While injectale vaccines remain the predominant format, they continue to face long-standing challenges such as suboptimal uptake and limited ability to curb viral transmission. Nasal spray vaccines—which induce mucosal immunity directly at the site of viral entry—represent an increasingly important direction for influenza prevention.

In September 2024, the US FDA granted authorisation for at-home administration of a related nasal spray influenza vaccine, paving the way for direct-to-consumer (DTC) distribution models. This regulatory milestone significantly improves convenience and accessibility for the public and creates favourable conditions for DIFF-flu's future global introduction.