Albert Einstein College of Medicine has received a USD 2.09 million NIAID award to advance RNA vaccine design against emerging viral pathogens with pandemic potential, including nairoviruses, hantaviruses, and paramyxoviruses. The funding supports Project 3 within the PROVIDENT consortium (U19AI181977), a multi-project cooperative agreement now in its third support year.

The grant targets three persistent limitations of RNA vaccines identified during the COVID-19 pandemic: suboptimal antigen expression driven by subcellular targeting choices, dose-dependent reactogenicity that complicates multi-antigen formulations, and an incomplete understanding of how antigen design principles generalize across virus families. Principal investigator Jesse Hong-Sae Erasmus will apply structure-guided and high-throughput screening methods to optimize cell-surface expression of RNA-encoded structural proteins from prototypic nairo-, hanta-, and paramyxoviruses, then extend validated designs to related viruses. A second aim evaluates whether multi-antigen compositions — pairing primary and secondary immune targets — can augment overall vaccine efficacy. The third aim directly compares innate immune activation and reactogenicity profiles between conventional mRNA and self-amplifying replicon RNA platforms across multiple encoded protein variants and virus-like particle constructs.

Albert Einstein College of Medicine, based in the Bronx, New York, is positioned within the PROVIDENT consortium to generate platform-level insights applicable beyond the three primary virus groups. Self-amplifying RNA remains an area of active development, with candidates from companies including Arctus Biotherapeutics and CSL Seqirus having advanced into clinical evaluation; characterizing the reactogenicity trade-offs of replicon versus conventional mRNA formats at the preclinical stage addresses a question with direct bearing on dose selection and tolerability in future trials.

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