SARS-CoV-2 continues to accumulate mutations to evade immunity, leading to breakthrough infections after vaccination. How researchers can anticipate the evolutionary trajectory of the virus in advance in the design of next-generation vaccines requires investigation. Here, we performed a comprehensive study of 11,650,487 SARS-CoV-2 sequences, which revealed that the SARS-CoV-2 spike (S) protein evolved not randomly but into directional paths of either high infectivity plus low immune resistance or low infectivity plus high immune resistance. The viral infectivity and immune resistance of variants are generally incompatible, except for limited variants such as Beta and Kappa. The Omicron variant has the highest immune resistance but showed high infectivity in only one of the tested cell lines. To provide cross-clade immunity against variants that undergo diverse evolutionary pathways, we designed a new pan-vaccine antigen (S pan ). S pan was designed by analyzing the homology of 2675 SARS-CoV-2 S protein sequences from the NCBI database before the Delta variant emerged. The refined S pan protein harbors high-frequency residues at given positions that reflect cross-clade generality in sequence evolution. Compared with a prototype wild-type (S wt ) vaccine, which, when administered to mice, induced serum with decreased neutralization activity against emerging variants, S pan vaccination of mice elicited broad immunity to a wide range of variants, including those that emerged after our design. Moreover, vaccinating mice with a heterologous S pan booster conferred complete protection against lethal infection with the Omicron variant. Our results highlight the importance and feasibility of a universal vaccine to fight against SARS-CoV-2 antigenic drift.
This paper presents a case study of the first geosynthetic reinforced soil-integrated bridge system (GRS-IBS) with with full-height rigid facings in China. Open graded gravel and biaxial geogrid were used for the GRS-IBS. Steel frame and 3D vegetation net were used as temporary facing support during construction of the GRS abutments. Full-height rigid facings were cast in place on strip foundations. Field monitoring results of vertical stress distribution for different construction stages and loading conditions are presented and discussed. For both bridge dead load and truck loads, measured incremental vertical stresses under the beam seat increase significantly with increasing elevation, especially for higher applied vertical stress. The calculated incremental vertical soil stresses using the Boussinesq solution are in reasonable agreement with the measured values, while the 2:1 stress distribution method overestimates the incremental stresses in the lower section of the abutment. The transferred vertical stresses from bridge load application for the GRS abutment with full-height rigid facing are larger than those for the GRS abutment with modular block facing near the top of the abutment, but are smaller near the bottom.
This paper presents two-dimensional (2D) and three-dimensional (3D) numerical simulations of a half-scale geosynthetic reinforced soil (GRS) bridge abutment during construction and bridge load application. The backfill soil was characterized using a nonlinear elasto-plastic model that incorporates a hyperbolic stress-strain relationship and the Mohr-Coulomb failure criterion. Geogrid reinforcements were characterized using linearly elastic elements with orthotropic behavior. Various interfaces were included to simulate the interaction between the abutment components. Results from the 2D and 3D simulations are compared with physical model test measurements from the longitudinal and transverse sections of a GRS bridge abutment. Facing displacements and bridge seat settlements for the 2D and 3D simulations agree well with measured values, with the 2D simulated values larger than the 3D simulated values due to boundary condition effects. Results from the 3D simulation are in reasonable agreement with measurements from the longitudinal and transverse sections. The 2D simulation can also reasonably capture the static response of GRS bridge abutments and is generally more conservative than the 3D simulation.
SARS-CoV-2 continued to spread globally along with different variants. Here, we systemically analyzed viral infectivity and immune-resistance of SARS-CoV-2 variants to explore the underlying rationale of viral mutagenesis. We found that the Beta variant harbors both high infectivity and strong immune resistance, while the Delta variant is the most infectious with only a mild immune-escape ability. Remarkably, the Omicron variant is even more immune-resistant than the Beta variant, but its infectivity increases only in Vero E6 cells implying a probable preference for the endocytic pathway. A comprehensive analysis revealed that SARS-CoV-2 spike protein evolved into distinct evolutionary paths of either high infectivity plus low immune resistance or low infectivity plus high immune resistance, resulting in a narrow spectrum of the current single-strain vaccine. In light of these findings and the phylogenetic analysis of 2674 SARS-CoV-2 S-protein sequences, we generated a consensus antigen (S6) taking the most frequent mutations as a pan-vaccine against heterogeneous variants. As compared to the ancestry SWT vaccine with significantly declined neutralizations to emerging variants, the S6 vaccine elicits broadly neutralizing antibodies and full protections to a wide range of variants. Our work highlights the importance and feasibility of a universal vaccine strategy to fight against antigen drift of SARS-CoV-2.
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