Aerosolized Ad5-nCoV booster vaccination elicited potent immune response against the SARS-CoV-2 Omicron variant after inactivated COVID-19 vaccine priming

The SARS-CoV-2 Omicron variant has become the dominant SARS-CoV-2 variant around the world and exhibits immune escape to current COVID-19 vaccines to some extent due to its numerous spike mutations. Here, we evaluated the immune responses to booster vaccination with intramuscular adenovirus-vectored vaccine (Ad5-nCoV), aerosolized Ad5-nCoV, a recombinant protein subunit vaccine (ZF2001) or homologous inactivated vaccine (CoronaVac) in those who received two doses of inactivated COVID-19 vaccines 6 months prior. We found that the Ad5-nCoV booster induced potent neutralizing activity against the wild-type virus and Omicron variant, while aerosolized Ad5-nCoV generated the greatest neutralizing antibody responses against the Omicron variant at day 28 after booster vaccination, at 14.1-fold that of CoronaVac, 5.6-fold that of ZF2001 and 2.0-fold that of intramuscular Ad5-nCoV. Similarly, the aerosolized Ad5-nCoV booster produced the greatest IFN{gamma} T-cell response at day 14 after booster vaccination. The IFN{gamma} T-cell response to aerosolized Ad5-nCoV was 12.8-fold for CoronaVac, 16.5-fold for ZF2001, and 5.0-fold for intramuscular Ad5-nCoV. Aerosolized Ad5-nCoV booster also produced the greatest spike-specific B cell response. Our findings suggest that inactivated vaccine recipients should consider adenovirus-vectored vaccine boosters in China and that aerosolized Ad5-nCoV may provide a more efficient alternative in response to the spread of the Omicron variant.

Neuropathic Pain Relieving in Rats by the Inhibition of Monomer of Lamiophlomis Rotata on AKT-mTOR Signaling Pathway in Spinal Dorsal Horn / 中国药师

Objective:To observe the effect of intrathecal administration of 8-O-acetyl-SM(8-OaS) on chronic neuropathic pain in rats by inhibiting the expression of protein kinase B(AKT)-mammalian target of rapamycin(mTOR) signaling pathway in spinal dorsal horn after spinal nerve ligation.Methods:The rat model of neuropathic pain was established by lumbar 5 spinal nerve ligation(SNL), and Von Frey filament was used to investigate the mechanical allodynia. Immunofluorescent histochemistry was adopted to investigate the distribution of pAKT and pmTOR in spinal dorsal horn. The protein levels of pAKT and pmTOR in spinal dorsal horn after drug ad-ministration were quantitatively determined by Western blot. Results: Compared with that in the sham group, the paw withdrawal threshold (PWT) significantly decreased(P<0.01),and the intrathecal administration of 8-OaS attenuated mechanical allodynia ob-viously during the first day and the seventh day after the operation(P<0.05). Meanwhile,double immunofluorescent staining showed the co-expression of pAKT and astrocytes marker glial fibrillary acidic protein(GFAP),and positive labeling of pmTOR was expressed in spinal astrocytes and neurons. The results of Western blot revealed that the protein levels of pAKT and pmTOR in spinal dorsal horn were significantly reduced after the treatment of 8-OaS. Conclusion:Intrathecal administration of 8-OaS attenuates the PWT of SNL-in-duced chronic neuropathic pain. The underlying mechanism of the potential anti-allodynia effect of 8-OaS may be related to the suppres-sion of spinal astrocytes via decreasing the phosphorylation of AKT-mTOR signaling pathway resulting in attenuating the development of neuropathic pain.