Evolution of National Influenza Vaccine Platform: From Comprehensive Preclinical Safety Validation of Trivalent Influenza Vaccine to Streamlined Immunogenicity of Quadrivalent Formulation.

Background

The Global Action Plan for Influenza Vaccines, launched by the World Health Organization in 2006, aimed to expand global manufacturing capacity, ensure equitable access to influenza vaccines, and reduce global vaccine shortages. The Institute of Virology, Vaccines and Sera "Torlak" was recognized as a partner and participated in a technology transfer programme to improve national production capabilities. Preclinical studies conducted in 2013 and 2014 provided comprehensive toxicological evidence supporting the safety of the trivalent influenza vaccine manufacturing platform. Nearly a decade later, this validated platform enabled the independent development of a quadrivalent influenza vaccine. Subsequent preclinical studies conducted in accordance with European Medicines Agency guidelines demonstrated preserved immunogenicity despite the inclusion of an additional antigen.

Methods

Preclinical evaluation included standard safety and immunogenicity assessments in animal models. Safety assessment included evaluation of systemic parameters (general health status, leukocyte profile, blood biochemistry, and histopathology) and local reactions. Immunogenicity of both trivalent and quadrivalent formulations was assessed using haemagglutination inhibition and microneutralization assays.

Results

No significant systemic or local adverse effects were observed. Both trivalent and quadrivalent formulations induced robust immune responses, with immunogenicity comparable to that of corresponding commercial vaccines.

Conclusions

These findings confirm the safety profile and demonstrate strong immunogenicity for both the trivalent and quadrivalent formulations, supporting the successful establishment of a national influenza vaccine platform, contributing to increased pandemic preparedness and sustainable influenza vaccine production.