Steinberg, I. | bioRxiv Science

bioRxiv2026

Intranasal Replicating Adenovirus type 4-SARS-CoV-2 Recombinants Induce Superior Immune Response Durability and Efficacy in Preclinical Testing Compared to Standard Intramuscular Vaccines

The portfolio of next generation COVID-19 vaccines would benefit from candidates that induce durable systemic and mucosal immune responses that would lessen person-to-person transmission. We constructed an intranasal (IN) replication-competent adenovirus type 4 recombinant platform to express SARS-CoV-2 Spike variants (Ad4-S) and assessed immunogenicity and efficacy in the Syrian hamster model. Although both IN Ad4-S and intramuscular (IM) vaccines (Ad26.CoV2.S and mRNA-1273) induced serum binding antibodies, only Ad4-S induced a robust mucosal response in the nasal cavity. IN Ad4-S vaccination induced serum neutralizing titers equivalent to or greater than IM vaccination but more durable up to 6 months. Upon challenge, IN immunization also resulted in less weight loss, greater breadth and durability of restriction of viral replication, and less lung pathology than IM immunization up to 268 days after immunization. These data support the potential of the IN Ad4 vaccine platform to reduce transmission of SARS-CoV-2 and other respiratory viruses with pandemic potential.

immunology↗

bioRxiv2023

Stimulus-induced theta band LFP oscillations format spiking outputs in the mouse accessory olfactory bulb

Social communication is crucial for survival of many species. In most vertebrates, a dedicated chemosensory system, the vomeronasal system (VNS), evolved to process ethologically relevant chemosensory cues. The first central VNS stage is the accessory olfactory bulb (AOB), which sends information to downstream brain regions via AOB mitral cells (AOB-MCs). Recent studies provided important insights about the functional properties of AOB-MCs, but little is known about the principles that govern their coordinated activity. Here, we recorded local field potentials (LFPs) and single unit activity in the AOB while presenting natural stimuli to adult male and female mice. Our recordings reveal prominent LFP theta band oscillatory episodes with a characteristic spatial pattern across the AOB. We find that the AOB network shows varying degrees of similarity to this pattern throughout an experiment, as a function of sensory stimulation. Analysis of LFP signal polarity and single unit activity indicate that oscillatory episodes are generated locally within the AOB, likely representing a reciprocal interaction between AOB-MCs and granule cells (GCs). Notably, spike times of many AOB-MCs are constrained to the negative LFP oscillation phase, in a manner that can drastically affect integration by downstream processing stages. Based on these observations, we propose that LFP oscillations may gate, bind, and organize outgoing signals from individual AOB neurons to downstream processing stages. Our findings suggest that, as in other neuronal systems and brain regions, population level oscillations play a key role in organizing and enhancing transmission of socially relevant chemosensory information.

neuroscience↗