Biology subjects

Caplan, A. B.

Publications and source records attributed to Caplan, A. B..

4 recordsLinked to original sources

bioRxiv2026

Atomic Layering Thermostable Antigen and Adjuvant (ALTA(R)) platform provides unique antigen delivery system through controlled release to improve immune response to vaccination

Prophylactic vaccines are commonly delivered using a multi-dose regimen with the goal of generating potent, durable protection against a specific pathogen. However, the requirement for multiple administrations can impede patient adherence and reduce overall protection. Designing a single-shot vaccine without compromising efficacy could significantly improve vaccine adherence and performance. Previously, it has been shown that atomic-layer deposition (ALD) of alumina (Al2O3) can be applied to spray dried, thermostabilized antigen-containing powders to produce alumina-coated vaccine particles that, when compared to a liquid control, elicit improved humoral immunity with response kinetics controlled by ALD-coat thickness. However, previous studies have not defined the particle release/antigen delivery profile of ALD-coated vaccines. The studies in this manuscript were designed to investigate how the kinetics of antigen release from ALD-coated vaccines impacts the timing and magnitude of the immune response relative to single- and multi-dose liquid vaccine regimens using two distinct antigens, Ovalbumin and the HIV-1 envelope trimer, N332-GT5 gp140. By combining longitudinal in vivo imaging and immunological readouts, we demonstrate that ALD-coated vaccines exhibit tunable, variable-rate release and deliver antigen in a unique, prolonged manner that results in an improved immune response to single-shot vaccination for difficult to target pathogens, such as HIV-1. Furthermore, using in vitro analytical methods, we confirmed the ability of our Atomic Layering and Thermostable Antigen and Adjuvant (ALTA(R)) platform to impart thermostability upon the N332-GT5 gp140 antigen, a clinically relevant HIV-1 immunogen, indicating the potential for ALTA(R) formulation to generate thermostable, single-dose vaccine products. Highlights- ALTA(R) microparticles provide sustained antigen delivery with variable release rates, which can be controlled by altering ALD-coat thickness - Sustained antigen release from thermostable, spray-dried ALTA(R) vaccine products impacts kinetics of humoral and cellular responses, and improves antigen-specific immunogenicity compared to single administration of liquid vaccine - ALTA(R) formulation imparts vaccine thermostability through spray-drying and ALD-coating to clinically relevant HIV-1 Env antigen, N332-GT5 gp140

immunology↗

bioRxiv2026

Subunit Vaccination Using Atomic Layering Thermostable Antigen and Adjuvant (ALTA(R)) Platform Elicits Enhanced Humoral and Cellular Immune Responses

AbstractCreating effective and thermostable vaccines is of significant relevance for public health. The Atomic Layering Thermostable Antigen and Adjuvant (ALTA(R)) platform combines spray drying to stabilize antigens in a sugar matrix followed by coating with atomic layer deposition (ALD) for temporal control over in vivo release. While these technologies have shown preliminary promise for different vaccine antigens, further characterizations of the immune response to ALTA(R) formulated antigens are still needed. Here, the immune response to ALTA(R) formulated antigens is described and compared to a set of adjuvanted liquid vaccine formulations that included Alhydrogel(R), AddaVax, and Alhydrogel(R)+CpG. The humoral and cell-mediated responses were measured by ELISA and flow cytometry. Increased and lasting antigen-specific antibody titers following administration of ALTA(R) containing ovalbumin (OVA) demonstrated robust and durable humoral response. Furthermore, ALTA(R) injected mice produced both IgG2c and IgG1 indicating a balanced Th1/Th2 response. Importantly, ALTA(R) OVA elicited robust humoral response at lower doses of aluminum than Alhydrogel(R). The most striking difference between ALTA(R) and the liquid vaccine formulations tested was a greater OVA-specific CD8+ T cell response observed at all antigen doses tested. Mechanistically, antigen encapsulation within ALTA(R) particles was critical for antibody production and CD8+ T cell responses as well as antigen capture by antigen-presenting cells (APCs) at the site of injection and draining lymph nodes. To test these concepts in a more physiological application, protein and polysaccharide vaccine antigens derived from a facultative intracellular bacterium Burkholderia pseudomallei, the causative agent of melioidosis, were formulated using the ALTA(R) platform. Compared to liquid vaccine formulations, ALTA(R) immunized mice showed enhanced antigen-specific antibody production and IFN-{gamma} secreting T cell responses using lower adjuvant doses of aluminum and CpG. Overall, ALTA(R) formulated protein and polysaccharide antigens elicited strong humoral and cell-mediated immunity suggesting potential broad applicability of the platform to vaccines against various diseases, including against cancer and infections from intracellular pathogens.

immunology↗

bioRxiv2024

Appraising the natural root-knot nematode resistance inSolanum sisymbriifolium, a wild relative of potato

Root-knot nematodes (RKNs) are a major pest of Solanum and other economically important crops worldwide. Two species of RKNs (Meloidogyne chitwoodi and Meloidogyne hapla) are persistent threats to potato growers of the United States. These RKNs infect potato roots and tubers, causing tuber blemishes that decrease potato market value and significantly impact the profitability of the infected potato crop. Due to environmental, health, and economic concerns, the longstanding control methods of using soil fumigants and post-plant nematicides are not favored by producers and consumers. Therefore, deploying RKN resistant cultivars is an alternative method to control RKN damage. However, there is no genetic resistance to RKN in commercially-available, cultivated potatoes. Therefore, the critical first step to breed a RKN resistant plant is to identify a genetic source of RKN resistance. A wild Solanum species, Solanum sisymbriifolium, also known as litchi tomato, can effectively control several agronomically important species of plant parasitic nematodes. Solanum sisymbriifolium is completely resistant to RKNs; only a few nematodes enter the plant roots and those that do, cannot establish a feeding site. To understand its ability to prevent RKNs from forming feeding sites, we performed transcriptomic analysis of S. sisymbriifolium roots inoculated with the Northern root knot nematode, M. hapla. Combined with the annotation of the recently published S. sisymbriifolium genome assembly, we discovered 13 differentially expressed resistance-related genes upon nematode inoculation. By transforming potatoes with candidate resistance genes from S. sisymbriifolium, we aim to understand the strong genetic resistance in S. sisymbriifolium and whether those genes are necessary and sufficient to drive resistance to RKN in potatoes. This information will help us understand gene functions and help us generate RKN resistance in relevant Solanum crops.

plant biology↗

bioRxiv2018

Assessment of an organ-specific de novo transcriptome of the nematode trap-crop, Solanum sisymbriifolium

Solanum sisymbriifolium, also known as \"Litchi Tomato\" or \"Sticky Nightshade,\" is an undomesticated and poorly researched plant related to potato and tomato. Unlike the latter species, S. sisymbriifolium induces eggs of the cyst nematode, Globodera pallida, to hatch and migrate into its roots, but then arrests further nematode maturation. In order to provide researchers with a partial blueprint of its genetic make-up so that the mechanism of this response might be identified, we used single molecule real time (SMRT) sequencing to compile a high quality de novo transcriptome of 41,189 unigenes drawn from individually sequenced bud, root, stem, and leaf RNA populations. Functional annotation and BUSCO analysis showed that this transcriptome was surprisingly complete, even though it represented genes expressed at a single time point. By sequencing the 4 organ libraries separately, we found we could get a reliable snapshot of transcript distributions in each organ. A divergent site analysis of the merged transcriptome indicated that this species might have undergone a recent genome duplication and re-diploidization. Further analysis indicated that the plant then retained a disproportionate number of genes associated with photosynthesis and amino acid metabolism in comparison to genes with characteristics of R-proteins or involved in secondary metabolism. The former processes may have given S. sisymbriifolium a bigger competitive advantage than the latter did.

bioinformatics↗