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Coronaviruses that infect humans belong to the Alpha-coronavirus (including HCoV-229E) and Beta-coronavirus (including SARS-CoV and SARS-CoV-2) genera. In particular, SARS-CoV-2 is currently a major threat to public health worldwide. However, no commercial vaccines against the coronaviruses that can infect humans are available. The spike (S) homotrimers bind to their receptors through the receptor-binding domain (RBD), which is believed to be a major target to block viral entry. In this study, we selected Alpha-coronavirus (HCoV-229E) and Beta-coronavirus (SARS-CoV and SARS-CoV-2) as models. Their RBDs were observed to adopt two different conformational states (lying or standing). Then, structural and immunological analyses were used to explore differences in the immune response with RBDs among these coronaviruses. Our results showed that more RBD-specific antibodies were induced by the S trimer with the RBD in the "standing" state (SARS-CoV and SARS-CoV-2) than the S trimer with the RBD in the "lying" state (HCoV-229E), and the affinity between the RBD-specific antibodies and S trimer was also higher in the SARS-CoV and SARS-CoV-2. In addition, we found that the ability of the HCoV-229E RBD to induce neutralizing antibodies was much lower and the intact and stable S1 subunit was essential for producing efficient neutralizing antibodies against HCoV-229E. Importantly, our results reveal different vaccine strategies for coronaviruses, and S-trimer is better than RBD as a target for vaccine development in Alpha-coronavirus. Our findings will provide important implications for future development of coronavirus vaccines. ImportanceOutbreak of coronaviruses, especially SARS-CoV-2, poses a serious threat to global public health. Development of vaccines to prevent the coronaviruses that can infect humans has always been a top priority. Coronavirus spike (S) protein is considered as a major target for vaccine development. Currently, structural studies have shown that Alpha-coronavirus (HCoV-229E) and Beta-coronavirus (SARS-CoV and SARS-CoV-2) RBDs are in lying and standing state, respectively. Here, we tested the ability of S-trimer and RBD to induce neutralizing antibodies among these coronaviruses. Our results showed that Beta-CoVs RBDs are in a standing state, and their S proteins can induce more neutralizing antibodies targeting RBD. However, HCoV-229E RBD is in a lying state, and its S protein induces a low level of neutralizing antibody targeting RBD. Our results indicate that Alpha-coronavirus is more conducive to escape host immune recognition, and also provide novel ideas for the development of vaccines targeting S protein.
RESUMO
Objective To evaluate the short and mid-term effects of fixing comminuted posterior acetabular wall fractures with structural autologous iliac bone graft combined with mini screws.Methods From January 2010 to January 2014,29 patients with comminuted posterior acetabular wall fracture were treated by structural autologous iliac bone graf combined with mini screws.They were 21 males and 8 females,with a mean age of 44.2 years (range,from 22 to 58 years).The mean time form injury to operation was 7.8 days (range,from 1 to 25 days).The operations were performed through the Kocher-Langenbeck approach,with the patients in the lying position on the uninjured side.The fragments were reduced and fixed by mini screws and the ischemic ones were removed.Structural autologous iliac bone graft was used to reconstruct the posterior wall of acetabulum before a reconstruction plate was applied to compress and maintain it.The functional outcomes were evaluated by the modified Merle d'Aubigne and Postel clinical grading system at the last follow-ups.The radiographs were graded according to the Matta criteria.Results By the Matta criteria,10 cases achieved excellent reduction,16 good reduction,and 3 poor reduction,giving a good to excellent rate of 89.7％.Of this series,29 patients were followed up for 31.5 months on average (range,from 12 to 48 months).By the modified Merle d'Aubigne and Postel criteria,the functional recovery was rated as excellent in 16 cases,good in 9,fair in 3 and poor in one,giving a good to excellent rate of 86.2％.Two cases developed femoral head necrosis according to the magnetic resonance imaging 18 months postoperation.Three patients developed traumatic arthritis two years postoperation.Five patients developed heterotopic ossification postoperation,with no obvious clinical symptoms.Two patient with injury to the sciatic nerve recovered 4 months postoperation.Conclusions Structural autologous iliac graft combined with mini screws can reconstruct the integrity and stability of the fractured acetabular posterior wall,avoiding osteonecrosis of the acetabulum.This surgical technique is effective and safe in treatment of comminuted fracture of the acetabular posterior wall.
