Biology subjects

Wiggins, J.

Publications and source records attributed to Wiggins, J..

3 recordsLinked to original sources

bioRxiv2025

Dual-Route H5N1 Vaccination Induces Systemic and Mucosal Immunity in Murine and Bovine Models

Since its discovery in U.S. dairy cattle in early 2024, the highly pathogenic H5N1 avian influenza (clade 2.3.4.4b) has spread widely among herds, causing major economic losses. This zoonotic event emphasizes the urgent need for H5 vaccines that elicit strong, durable, cross-reactive immune responses in cattle, especially young calves. To address this, we immunized mice and cattle with a centralized consensus H5 vaccine, designed to localize to the central node of the human H5 phylogenetic tree. The vaccine was delivered using serotype-switched adenoviral vectors in a prime-boost regimen, combined with intramuscular and intranasal coadministration to target systemic and mucosal immunity and elicit strong humoral and cellular immune responses. This approach strategically integrates multiple innovative features: centralized consensus immunogens, mucosal targeting, and vector serotype switching that are aimed at maximizing immune protection against H5N1 viruses. Our results show that vaccination elicited strong humoral and cellular immunity in both mice and calves. In challenge experiments, vaccinated mice were fully protected against lethal infection with multiple divergent H5N1 strains, including the 2024 bovine isolate (A/bovine/Ohio/B24OSU-439/2024). Given that vaccine induced immunity was consistent across species, these results support the translatability of the mouse model findings to cattle. Overall, our findings represent a promising approach for immunizing cattle and other key livestock against HPAI H5N1, mitigating agricultural losses, and reducing the risk of zoonotic transmission. Significance StatementH5N1 influenza A virus is a serious pathogen recently detected in many mammals, including cattle. It transmits sporadically to humans and causes major economic losses in dairy and poultry industries, raising global concern. No H5N1 vaccines are currently licensed for cattle. To address this gap, we tested a centralized consensus H5 (H5CC) vaccine, previously effective in mice and swine. Using multiple Adenovirus vectors, we delivered H5CC intramuscularly and intranasally to one-week-old calves. The vaccines induced strong humoral and cellular immune responses, essential for preventing infection and limiting transmission. These findings highlight the vaccines potential to reduce agricultural losses and remove cattle as a newly established reservoir for zoonotic spread, providing a promising strategy for mitigating pandemic risk.

immunology↗

bioRxiv2022

Minimally invasive delivery of peptides to the spinal cord for behavior modulation

The blood-spinal cord barrier (BSCB) tightly regulates molecular transport from the blood to the spinal cord. Herein, we present a novel approach for transient modulation of BSCB permeability and localized delivery of peptides into the spinal cord for behavior modulation with high spatial resolution. This approach utilizes optical stimulation of vasculature-targeted nanoparticles and allows delivery of BSCB-nonpermeable molecules into the spinal cord without significant glial activation or impact on animal locomotor behavior. We demonstrate minimally invasive light delivery into the spinal cord using an optical fiber and BSCB permeability modulation in the lumbar region. Our method of BSCB modulation allows delivery of bombesin, a centrally-acting and itch-inducing peptide, into the spinal cord and induces a rapid and transient increase in itching behaviors in mice. This minimally invasive approach enables behavior modulation without genetic modifications and is promising for delivering a wide range of biologics into the spinal cord for behavior modulation and potentially therapy. Significance StatementSpinal cord diseases and disorders are common and cause significant disability, including chronic pain, paralysis, cognitive impairment, and mortality. The blood-spinal cord barrier is a considerable challenge for delivery by systemic therapeutic administration. We developed an optical approach for effectively and safely delivering molecules to the spinal cord to overcome this barrier. The fiberoptic method is minimally invasive and overcomes challenges that previous technologies face, including the complicated bone structure and standing waves that complicate BSCB opening using ultrasound. Optical stimulation offers unprecedented spatial resolution for the precise delivery in intricate spinal cord structures. Significantly, our approach modulates animal behavior (i.e., itch) without genetic modifications and demonstrates the potential for delivery of biologics such as peptides into the spinal cord.

neuroscience↗

bioRxiv2018

Evidence for sex microchromosomes in a species with temperature-influenced sex determination (Crotaphytus collaris)

The characteristics of a species evolution can be powerfully influenced by its mode of sex determination and, indeed, sex determination mechanisms vary widely among eukaryotes. In non-avian reptiles, sex was long thought to be determined bimodally, either by temperature or genetics. Here we add to the growing evidence that sex determining mechanisms in reptiles fall along a continuum rather than existing as a mutually exclusive dichotomy. Using qPCR, we demonstrate that the lizard Crotaphytus collaris possesses sex-based gene dosage consistent with the presence of sex michrochromosomes, despite that extreme incubation temperatures can influence hatchling sex ratio. Our results suggest a temperature override that switches genotypic females to phenotypic males at high and low temperatures.

ecology↗