Glyco-engineered virus-like particles (VLPs) to improve vaccine efficacy in eliciting immune responses against viral pathogens by masking off-target epitopes.
Engineered alphavirus‑like particles offer a promising solution to the growing demand for safer, more potent, and adaptable vaccine platforms. VLPs are already valued for their strong immune activation and safety, but traditional versions face challenges with stability and scalable manufacturing. This engineered approach addresses those limitations, enabling more reliable production and stronger, longer‑lasting immune responses. The need is especially urgent for diseases without effective vaccines—most notably HIV‑1, where prevention still relies on chronic antiretroviral therapy. A successful HIV vaccine would address a major global unmet need and represent a significant commercial opportunity. The platform also applies to large and continually evolving markets such as influenza and SARS‑CoV‑2, where frequent viral changes drive ongoing vaccine demand. Overall, engineered VLPs position this technology as a compelling next‑generation solution with broad public health and market potential.
Emory researchers have developed an engineered alphavirus‑like particle (VLP) platform designed to enhance immune responses against the HIV‑1 fusion peptide (FP), a small sub-immunodominant peptide target for generating broad and potent antibodies. Traditional sequential immunization approaches often trigger strong off‑target responses to conserved carrier epitopes, diverting immunity away from the intended FP. To overcome this, the team applies glycan engineering to mask shared off‑target epitopes across multiple alphavirus VLP backbones. The HIV‑1 FP is inserted into the VLP surface proteins, enabling the creation of distinct immunogens derived from different alphavirus scaffolds. Sequential administration of these heterologous VLPs increases both the magnitude and breadth of FP‑directed antibody responses. In preclinical studies, this approach produced stronger FP‑binding titers than repeated boosting with a single VLP type. Glycan masking further improved these responses, demonstrating that reducing recognition of shared carrier epitopes can more effectively focus immunity on the HIV‑1 FP.[JB2.1][KR2.2][KR3.1] Ongoing NHP studies also show strong immune responses to the target peptide. [
Publication Seo-Ho Oh, Dedeepya R. Gudipati, Wei Shi, Peng Zhao, Winston Wu, Jeffrey C. Boyington, Hardik K. Nariya, Emily G. McGhee, Tala Azzam, Vedhika Raghunathan, Chumeng Yang, Catherine Yang, Christian Lee, Jane D. Kim, Tongqing Zhou, John R. Mascola, Lance Wells, Rui Kong. 2025. Novel HIV-1 fusion peptide immunogens using glycan-engineered alphavirus-like particles. npj Vaccines. 10(1): p. 232. [PMC12618464].