Review identifies conserved targets, advanced platforms, and translational hurdles for universal influenza and pan-coronavirus vaccines.

Influenza and coronaviruses pose significant global health threats, causing hundreds of thousands to millions of deaths annually. Current strain-specific vaccines are reactive, failing to address antigenic drift, reassortment, or zoonotic emergence. This necessitates a paradigm shift towards universal vaccines that target evolutionarily conserved viral epitopes, aiming for durable, broad-spectrum protection across diverse strains and subtypes. This review addresses the critical need for an integrated analysis of universal vaccine development for both viral families.

This study conducted a structured narrative review, systematically searching PubMed, EMBASE, and ClinicalTrials.gov for literature published between 2015 and June 2026. The search utilized MeSH and free-text terms including universal influenza vaccines, pan-coronavirus vaccines, mRNA vaccine platforms, hemagglutinin stalk, neuraminidase, M2e, receptor-binding domain (RBD), fusion peptide, S2 subunit, and broadly neutralizing antibodies. The review included peer-reviewed original research, Phase I-III clinical trial reports, and authoritative reviews, excluding non-English or preclinical-only studies.

The review provides an integrated synthesis of universal influenza vaccine (UIV) and pan-coronavirus vaccine (UCV) development, highlighting key conserved immunological targets. For influenza, these include the hemagglutinin stalk, neuraminidase, and M2e protein. For coronaviruses, targets encompass the receptor-binding domain (RBD), fusion peptide, and S2 subunit of the spike protein, all aimed at eliciting broadly neutralizing antibodies. The analysis critically evaluated advanced platform technologies, such as mRNA vaccine platforms, and their current status within Phase I-III clinical pipelines for both UIVs and UCVs. It detailed the challenges in achieving broad, durable immunity and the complexities of clinical development and regulatory pathways for these novel vaccine approaches.

The review identified convergent scientific principles guiding universal vaccine design, alongside divergent translational barriers unique to each viral family, informing a unified pandemic preparedness strategy.