Biology subjects

Lemnios, A. A.

Publications and source records attributed to Lemnios, A. A..

3 recordsLinked to original sources

bioRxiv2026

Atomic layer deposition for core-shell microparticle vaccines enabling programmable antigen delivery to lymph nodes enhance humoral immune responses

Technologies that simplify complex dosing regimens as single-shot immunizations may be important for vaccines against difficult to neutralize pathogens. Here we characterized delivery mechanisms of core-shell microparticles comprising clinically-relevant HIV immunogen formulations spray-dried to form solid spherical microparticles and subsequently coated with a nanoscopic alumina shell using atomic layer deposition (ALD). ALD particles exhibited a time delay in antigen release programmed by the alumina shell followed by prolonged antigen release, which steadily accumulated in antigen-presenting cells at the injection site and draining lymph nodes and accumulated on follicular dendritic cells in B cell follicles. ALD vaccines elicited continuous expansion of antigen-specific germinal center B cells over 8 weeks, serum antibody responses with >10-fold slower antigen-binding off-rates, and 2-fold more long-lived plasma cells compared to traditional bolus vaccination with potent adjuvants. Single administration ALD technology thus promotes key events in the primary immune response important for vaccines against HIV and other challenging pathogens.

immunology↗

bioRxiv2025

Engineering gene expression dynamics via self-amplifying RNA with drug-responsive non-structural proteins

The design of gene therapies with drug-regulatable expression of therapeutic payloads is of interest for diverse applications. We hypothesized that a regulated expression system based on alphavirus-derived self-amplifying RNAs (saRNAs), which encode 4 non-structural proteins (nsPs) that copy the RNA backbone to enable sustained expression, would have advantages in safety and simplicity of delivery. Here we designed saRNAs where payload expression is regulated by the FDA-approved drug trimethoprim (TMP), by fusing TMP-responsive degradation domains (DDs) to nsPs to regulate RNA self-amplification. Screening a library of nsP-DD fusions, we identified an optimal design with DDs fused to nsP2, nsP3, and the payload, achieving a high fold-change in expression level in response to TMP and low expression in the off state. In mice, this saRNA circuit enabled diverse dynamic expression patterns in response to oral TMP. Implementing this circuit for controlled expression of an HIV antigen, an escalating TMP regimen significantly enhanced germinal center responses critical for B cell affinity maturation. This drug- regulated RNA technology holds potential for vaccines, immunotherapies, and gene therapies.

bioengineering↗

bioRxiv2021

Engineered SARS-CoV-2 receptor binding domain improves immunogenicity in mice and elicits protective immunity in hamsters

Global containment of COVID-19 still requires accessible and affordable vaccines for low- and middle-income countries (LMICs).1 Recently approved vaccines provide needed interventions, albeit at prices that may limit their global access.2 Subunit vaccines based on recombinant proteins are suited for large-volume microbial manufacturing to yield billions of doses annually, minimizing their manufacturing costs.3 These types of vaccines are well-established, proven interventions with multiple safe and efficacious commercial examples.4-6 Many vaccine candidates of this type for SARS-CoV-2 rely on sequences containing the receptor-binding domain (RBD), which mediates viral entry to cells via ACE2.7,8 Here we report an engineered sequence variant of RBD that exhibits high-yield manufacturability, high-affinity binding to ACE2, and enhanced immunogenicity after a single dose in mice compared to the Wuhan-Hu-1 variant used in current vaccines. Antibodies raised against the engineered protein exhibited heterotypic binding to the RBD from two recently reported SARS-CoV-2 variants of concern (501Y.V1/V2). Presentation of the engineered RBD on a designed virus-like particle (VLP) also reduced weight loss in hamsters upon viral challenge.

molecular biology↗