A Hyper attenuated, highly Immunogenic Influenza A Virus Vector Platform.
Core Technology
UniFluVec is a proprietary influenza A virus vector platform engineered through targeted modifications of the NS1 and NEP genes, combining hyper attenuation with enhanced immunogenicity.
These modifications strongly restrict viral replication while promoting potent activation of innate immunity, including interferon, cytokine, and chemokine responses. This intrinsic immunostimulatory activity supports the development of robust adaptive immune responses.
Importantly, despite its highly attenuated phenotype, UniFluVec retains the ability to express viral antigens and inserted transgenes, enabling antigen-specific immune responses.
In a randomized, double-blind, placebo-controlled Phase I clinical trial involving 60 healthy adults, intranasally administered UniFluVec was well tolerated at two dose levels. No detectable vaccine-virus shedding was reported, consistent with a replication-restricted phenotype in humans. The trial assessed safety and tolerability, not protective efficacy.
Immunological Properties
UniFluVec combines potent innate immune stimulation with broad adaptive immune responses, including cross-reactive antibodies, antigen-specific T cells, and Th1-biased immunity.
Intranasal administration of UniFluVec induces robust mucosal immunity, including the formation of tissue-resident memory T cells (Trm) in the respiratory tract. Preclinical studies in mouse models demonstrate that these cells play a central role in mediating cross-protective immunity against antigenically divergent influenza A strains.
UniFluVec also demonstrates strong immunogenicity following parenteral administration. In preclinical minipig studies, intradermal immunization induced systemic T-cell responses and antigen specific cellular responses in the lungs, suggesting potential to establish respiratory immune responses without direct mucosal administration.
Platform Applications
The combination of hyperattenuation, enhanced immunogenicity, and antigen expression supports three complementary applications.
1. Broad-Spectrum Influenza Vaccines
UniFluVec is being developed as a standalone influenza A vaccine designed to elicit cross reactive antibody and T-cell responses and provide protection against heterologous influenza strains, including strains with pandemic potential.
2. Viral Vector Vaccines
UniFluVec provides a platform for the delivery and expression of heterologous antigens. Related influenza viral vectors expressing pathogen-specific antigens have demonstrated protective activity against SARS-CoV-2 and RSV in preclinical models, supporting further development of vaccine candidates for respiratory pathogens. These findings do not establish efficacy of every proposed construct or clinical protection in humans.
3. Immune Enhancement
Through its intrinsic ability to activate innate immunity and support Th1-biased responses, UniFluVec offers potential as an immune enhancer for co-administered recombinant proteins and other vaccine antigens. This application is under preclinical investigation; enhancement of responses to co-administered proteins has not yet been established.
Future Research Directions
Beyond antigen-specific immunity, Capricorn is investigating whether the innate immune activation associated with UniFluVec may support broader antiviral responsiveness in the respiratory tract. The breadth, mechanisms, and durability of such effects including any contribution of trained innate immunity remain research questions, not established clinical benefits.
Clinical and Preclinical Development
A randomized, double-blind, placebo-controlled Phase I clinical study evaluated intranasal UniFluVec in 60 healthy adults. Two dose levels were assessed using two administrations 21 days apart. The published study provides initial human safety and reactogenicity evidence and reported no detectable vaccine-virus shedding; it does not establish protection against influenza or other respiratory viruses.
Preclinical studies have demonstrated cross-protection against heterologous influenza A virus challenge in ferrets, including H3N2 and highly pathogenic H5N1. In the NIAID supported H5N1 study, all UniFluVec immunized ferrets survived challenge despite no detectable H5N1 neutralizing antibodies; this was protection against severe disease, not prevention of infection. The immune mechanisms responsible were not directly established.
Manufacturing Compatibility
UniFluVec is designed for production using established influenza vaccine manufacturing technologies, including conventional embryonated chicken egg-based processes. An egg based production route has already supported the clinical development of UniFluVec, providing a basis for adapting existing influenza vaccine production infrastructure rather than requiring a fundamentally new manufacturing platform. Facility specific adaptation, process qualification, and regulatory compliance remain necessary.
Capricorn also has access to the proprietary AEX-1 Vero derived cell substrate, developed by its subsidiary NuCell GmbH. For evaluated influenza virus constructs, AEX-1 has achieved yields approaching those obtained in embryonate chicken eggs, offering an alternative cell-based route for UniFluVec family vectors when required. This capability is subject to construct specific process development and qualification.