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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.
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Here,we reported a case of term infant with unilateral congenital microphthalmia (CM).Physical examination conducted on 2 d after birth showed that the left eye was barely open and the eye socket was deeper than the right.Meanwhile,the cornea of the left eye was not completely exposed and the light reflex could not be elicited.Ophthalmology consultation,ultrasound and CT scan were conducted,and CM was finally diagnosed since the infant was found to have a small eyeball and shortened axial length,accompanying by pathological changes in the lens,vitreous body and retina.This case suggested that detailed physical examination should be carried out,especially for the eyes,including orbit and eyelid,presence or absence of secretion or concealed eyeball,together with medical imaging techniques technology,to ensure an early detection and diagnosis of CM in neonates.
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Objective To investigate the distribution characteristics in the positive ratio distribution of serum allergen specific immunoglobulin E (sIgE) in atopic dermatitis children with multiple sensitization factors,which could help to assess the atopic condition and offer recommendation for the avoidance of allergens.Methods A total of 90 children with atopic dermatitis were enrolled(male 66,female 24,aged 0.3-16.1 years).All the patients were divided into 3 groups according to the patients' age:0-3 years old group (48 patients),4-7 years old group (31 patients),8-16 years old group (11 patients).The serum sIgE levels of 29 kinds of food and inhalation allergens in each patient were detected by the UniCAP 250 quantified IgE measurement system.Results The positive ratio of each food allergen in all the patients were as follows:55.6％ (50/90 cases) for egg white,42.2％ (38/90 cases) for milk,32.2％ (29/90 cases) for egg yolk,12.2％ (11/90 cases) for shrimp,11.1％ (10/90 cases) for crab,7.8％ (7/90 cases) for chicken,4.4％ (4/90 cases) for fish,54.4％ (49/90 cases) for wheat,37.8％ (34/90 cases) for peanut,34.4％ (31/90 cases) for soybean,33.3％ (30/90 cases) for tomato and 28.9％ (26/90 cases) for peach.The positive ratio of each inhalation allergen in all the patients were as follows:51.1％ (46/90 cases) for house dust,45.6％ (41/90 cases) for alternaria alternata,41.1％ (37/90 cases) for dermatophagoides pteronyssinus,40％ (36/90 cases) for dermatophagoides farinae,33.3％ (30/90 cases) for dog dander,28.9％ (26/90 cases) for cockroach,27.8％ (25/90 cases) for cat dander,21.9％ (19/90 cases) for blomia tropicalis,36.7％ (33/90 cases) for ambrosia elatior,34.4％ (31/90 cases) for white ash,32.2％ (29/90 cases) for london plane,32.2％ (29/90 cases) for artemisia vulgaris,31.1％ (28/90 cases) for common silver birch,27.8％ (25/90 cases) for willow,25.6％ (23/90 cases) for mountain juniper,25.6％ (23/90 cases) for humulus scandens and 25.6％ (23/90 cases) for chenopodium album.The positive ratios of sIgE for egg white,milk,egg yolk of patients in the 0-3 years old group were higher than those in the 4-7 years old group and 8-16 years old group (x2 =29.27,15.98,18.58,all P ＜ 0.05).The positive ratios of sIgE for dermatophagoides pteronyssinus,dermatophagoides farinae,blomia tropicalis,cat dander,mountain juniper,humulus scandens of patients in the 8-16 years old group were higher than those in the 0-3 years old group and 4-7 years old group (x2 =12.94,14.31,7.77,7.65,9.41,6.93,all P ＜ 0.05).The positive ratios of sIgE for food allergens and animal dander in the patients of diagnosed as atopic dermatitis alone were higher than those of diagnosed as atopic dermatitis combined with asthma or allergic rhinitis.The positive ratios of sIgE for common inhalation allergens in the patients diagnosed as atopic dermatitis alone were lower than those diagnosed as atopic dermatitis combined with asthma or allergic rhinitis.Conclusions Allergens such as animal protein,house dust,mites and molds are the main sensitization allergens for atopic dermatitis children with multiple sensitization factors.Atopic dermatitis children in 0-3 years old group often presented sensitiveto food allergens,while those in 8-16 years old group are more commonly sensitive to inhalation allergens.Patients diagnosed as atopic dermatitis alone are often presented sensitive to food allergens and animal dander,while those diagnosed with asthma or allergic rhinitis are more commonly sensitive to inhalant allergens.
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<p><b>OBJECTIVE</b>The prevalence of allergic asthma has been rising continually which is correlated with the increasingly closed living environment. House dust mites are the major sources of indoor aeroallergens which induce asthma in sensitized people. To monitor the seasonal variation of house dust mite (HDM)-allergens exposure level in the asthmatic children, which was evaluated to show its correlation with the level of asthma control, HDM allergic sensitization and fraction of exhaled nitric oxide, and to provide basic data for HDM environmental control.</p><p><b>METHOD</b>A total of 48 HDM-allergic asthmatic children were enrolled from the asthma clinic in the hospital from March 2011 to January 2012 (boys 34 and girls 14, aging from 3 to 14 years, mean age 8 years and 4 months) in the present study. Dust samples from mattresses, pillows, bedroom floor, living room floor and sofas were collected in each season within one year in the household of all the enrolled patients. The concentrations of Der p 1 and Der f 1 were measured by the enzyme-linked immunosorbent assay (ELISA). To record the Asthma Control Test (ACT) score or Children Asthma Control Test (C-ACT) score for each patient and to collect the data of doctor monitoring asthma control level each time when the patient was clinic visited. The concentration and its classification of the serum specific IgE to HDM was determined by fluoroenzyme-immunometric assay.</p><p><b>RESULT</b>The average concentration of Der f 1 of all dust samples was significantly higher than that of Der p 1 (0.13 µg/g vs 0.02 µg/g, P < 0.05). The concentrations of Der f 1 from mattresses, pillows and sofas dust samples were significantly higher than those from bedroom floor and living room floor dust samples (0.69 µg/g, 0.42 µg/g and 0.22 µg/g vs 0.07 µg/g and 0.07 µg/g, P < 0.05). The Der f 1 exposure level from mattress dusts in summer but no others was negatively correlated with asthma control level (r = -0.318, P = 0.036). The Der f 1 exposure level from any area dusts in summer and the Der p 1 exposure level from pillows dusts in autumn was negatively correlated with ACT/C-ACT score respectively. The Der f 1 from mattress dusts in winter was positively correlated with classification of sIgE to Der f 1. The Der p 1 exposure level from most areas in each season was positively correlated with classification of sIgE to Der f 1 and Der P 1.</p><p><b>CONCLUSION</b>Der f 1 was the predominant mite allergen in household dust and mainly came from mattresses, pillows and sofas. The role of the HDM allergen exposure level on the asthma control level and HDM allergic sensitization for the asthmatic children were depended on its area, season and HDM species, which suggested that the future assessment of clinical effect by the HDM environmental control should consider these factors.</p>
