Bridging the vaccine gap: Scientific and technological advances for diseases lacking effective vaccines

Despite remarkable achievements in infectious disease control, more than 20 major pathogens responsible for significant global morbidity and mortality remain without licensed, effective vaccines. This so-called 'vaccine gap' disproportionately burdens low- and middle-income countries (LMICs), exacerbating health inequities and threatening global pandemic preparedness. This review comprehensively examines scientific and technological advances that are actively bridging the vaccine gap, with emphasis on novel platform technologies, immunological innovations, and translational strategies. We conducted a systematic narrative review of literature published between 2015 and 2024, encompassing peer-reviewed articles, WHO reports, clinical trial registries, and regulatory agency databases. Six transformative technology clusters were identified: (1) mRNA and self-amplifying RNA (saRNA) platforms enabling rapid antigen production; (2) viral-vectored vaccines with improved immune breadth; (3) structure-guided antigen design using cryo-electron microscopy and artificial intelligence (AI)-driven protein engineering; (4) broadly neutralising monoclonal antibodies as surrogate vaccine benchmarks; (5) mucosal and inhalable delivery systems targeting tissue-resident immunity; and (6) combination adjuvant systems amplifying magnitude and durability of protective responses. Clinical translation is exemplified by candidates against HIV-1, tuberculosis (TB), respiratory syncytial virus (RSV) in infants, and Plasmodium falciparum malaria. Convergence of AI-assisted rational antigen design, next-generation mRNA platforms, and innovative adjuvant-delivery pairings represents a paradigm shift toward vaccinatable diseases previously considered intractable. Equitable access frameworks and regulatory harmonisation across LMICs remain critical unresolved challenges.