A Nasal Vaccine Candidate, Containing Three Antigenic Regions from SARS-CoV-2, to Induce a Broader Response.
Yadira LobainaRong ChenEdith SuzartePanchao AiAlexis MusacchioYaqin LanGlay ChineaChangyuan TanRicardo SilvaGerardo Guillen NietoKe YangWen LiYasser PereraLisset HermidaPublished in: Vaccines (2024)
A chimeric protein, formed by two fragments of the conserved nucleocapsid (N) and S2 proteins from SARS-CoV-2, was obtained as a recombinant construct in Escherichia coli . The N fragment belongs to the C-terminal domain whereas the S2 fragment spans the fibre structure in the post-fusion conformation of the spike protein. The resultant protein, named S2NDH, was able to form spherical particles of 10 nm, which forms aggregates upon mixture with the CpG ODN-39M. Both preparations were recognized by positive COVID-19 human sera. The S2NDH + ODN-39M formulation administered by the intranasal route resulted highly immunogenic in Balb/c mice. It induced cross-reactive anti-N humoral immunity in both sera and bronchoalveolar fluids, under a Th1 pattern. The cell-mediated immunity (CMI) was also broad, with positive response even against the N protein of SARS-CoV-1. However, neither neutralizing antibodies (NAb) nor CMI against the S2 region were obtained. As alternative, the RBD protein was included in the formulation as inducer of NAb. Upon evaluation in mice by the intranasal route, a clear adjuvant effect was detected for the S2NDH + ODN-39M preparation over RBD. High levels of NAb were induced against SARS-CoV-2 and SARS-CoV-1. The bivalent formulation S2NDH + ODN-39M + RBD, administered by the intranasal route, constitutes an attractive proposal as booster vaccine of sarbecovirus scope.
Keyphrases
- sars cov
- respiratory syndrome coronavirus
- protein protein
- escherichia coli
- drug delivery
- amino acid
- advanced non small cell lung cancer
- endothelial cells
- high glucose
- metabolic syndrome
- coronavirus disease
- dna methylation
- gene expression
- diabetic rats
- adipose tissue
- high resolution
- photodynamic therapy
- staphylococcus aureus
- tyrosine kinase
- high fat diet induced
- insulin resistance
- oxidative stress
- molecular dynamics simulations
- liquid chromatography
- induced pluripotent stem cells
- biofilm formation