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The gist and details of an event are both important for us to establish and maintain episodic memory. On the other hand, episodic memory is influenced by both external and internal factors, such as memory cue and intrinsic motivation. To what extent these factors and their interaction modulate memory and forgetting of gist and detailed information remains unclear. In this study, 29 participants watched film clips accompanied by either gist or detailed cues and rated their interest in these clips. Their memories of gist and detailed information were tested after 10 min, 1 day, and 1 week. The results showed that memory cue modulated the forgetting of gist and detailed memories. Specifically, when gist cues were used, gist memory was forgotten more slowly than detailed memory. When detailed cues were used, detailed memory was forgotten more slowly than gist memory. Differently, the subjective interest in the clips enhanced memory accuracy irrespective of memory type but did not influence the forgetting of gist and detailed memories. Moreover, there was a significant interaction between memory cue and interest, showing that gist cues enhanced memory than detailed cues only for low-interest clips. These results suggest that external and internal factors have differential effects on memory and forgetting, and the effectiveness of external factors depends on the state of intrinsic motivation. The significant interplay of different factors in influencing the remembering or forgetting of gist and detailed memories provides potential ways to enhance memory and retention of gist and detailed information.

Abstract Since the first outbreak in December 2019, SARS-CoV-2 has been constantly evolving and five variants have been classified as Variant of Concern (VOC) by the World Health Organization (WHO). These VOCs were found to enhance transmission and/or decrease neutralization capabilities of monoclonal antibodies and vaccine-induced antibodies. Here, we successfully designed and produced a recombinant COVID-19 vaccine in CHO cells at a high yield. The vaccine antigen contains four hot spot substitutions, K417N, E484K, N501Y and D614G, based on a prefusion-stabilized spike trimer of SARS-CoV-2 (S-6P) and formulated with an Alum/CpG 7909 dual adjuvant system. Results of immunogenicity studies showed that the variant vaccine elicited robust cross-neutralizing antibody responses against SARS-CoV-2 prototype (Wuhan) strain and all 5 VOCs. It further, stimulated a TH1 (T Helper type 1) cytokine profile and substantial CD4+ T cell responses in BALB/c mice and rhesus macaques were recorded. Protective efficacy of the vaccine candidate was evaluated in hamster and rhesus macaque models of SARS-CoV-2. In Golden Syrian hamsters challenged with Beta or Delta strains, the vaccine candidate reduced the viral loads in nasal turbinates and lung tissues, accompanied by significant weight gain and relieved inflammation in the lungs. In rhesus macaque challenged with prototype SARS-CoV-2, the vaccine candidate decreased viral shedding in throat, anal, blood swabs over time, reduced viral loads of bronchus and lung tissue, and effectively relieved the lung pathological inflammatory response. Together, our data demonstrated the broadly neutralizing activity and efficacy of the variant vaccine against both prototype and current VOCs of SARS-CoV-2, justifying further clinical development.

Abstract Emerging SARS-CoV-2 variants are the most serious problem for COVID-19 prophylaxis and treatment. To determine whether the SARS-CoV-2 vaccine strain should be updated following variant emergence like seasonal flu vaccine, the changed degree on antigenicity of SARS-CoV-2 variants and H3N2 flu vaccine strains was compared. The neutralization activities of Alpha, Beta and Gamma variants’ spike protein-immunized sera were analysed against the eight current epidemic variants and 20 possible variants combining the top 10 prevalent RBD mutations based on the Delta variant, which were constructed using pseudotyped viruses. Meanwhile, the neutralization activities of convalescent sera and current inactivated and recombinant protein vaccine-elicited sera were also examined against all possible Delta variants. Eight HA protein-expressing DNAs elicited-animal sera were also tested against eight pseudotyped viruses of H3N2 flu vaccine strains from 2011–2019. Our results indicate that the antigenicity changes of possible Delta variants were mostly within four folds, whereas the antigenicity changes among different H3N2 vaccine strains were approximately 10–100-fold. Structural analysis of the antigenic characterization of the SARS-CoV-2 and H3N2 mutations supports the neutralization results. This study indicates that the antigenicity changes of the current SARS-CoV-2 may not be sufficient to require replacement of the current vaccine strain.

Abstract Background To determine an appropriate dose of, and immunization schedule for, a vaccine SCoK against COVID‐19 for an efficacy study; herein, we conducted randomized controlled trials to assess the immunogenicity and safety of this vaccine in adults. Methods These randomized, double‐blind, placebo‐controlled phase 1 and 2 trials of vaccine SCoK were conducted in Binhai District, Yan City, Jiangsu Province, China. Younger and older adult participants in phase 1 and 2 trials were sequentially recruited into different groups to be intramuscularly administered 20 or 40 μg vaccine SCoK or placebo. Participants were enrolled into our phase 1 and 2 studies to receive vaccine or placebo. Results No serious vaccine‐related adverse events were observed in either trial. In both trials, local and systemic adverse reactions were absent or mild in most participants. In our phase 1 and 2 studies, the vaccine induced significantly increased neutralizing antibody responses to pseudovirus and live SARS‐CoV‐2. The vaccine induced significant neutralizing antibody responses to live SARS‐CoV‐2 on day 14 after the last immunization, with NT50s of 80.45 and 92.46 in participants receiving 20 and 40 μg doses, respectively; the seroconversion rates were 95.83% and 100%. The vaccine SCoK showed a similar safety and immunogenicity profiles in both younger participants and older participants. The vaccine showed better immunogenicity in phase 2 than in phase 1 clinical trial. Additionally, the incidence of adverse reactions decreased significantly in phase 2 clinical trial. The vaccine SCoK was well tolerated and immunogenic.

Although hundreds of different adjuvants have been tried, aluminum-containing adjuvants are by far the most widely used currently. It is worth mentioning that although aluminum-containing adjuvants have been commonly applied in vaccine production, their acting mechanism remains not completely clear. Thus far, researchers have proposed the following mechanisms: (1) depot effect, (2) phagocytosis, (3) activation of pro-inflammatory signaling pathway NLRP3, (4) host cell DNA release, and other mechanisms of action. Having an overview on recent studies to increase our comprehension on the mechanisms by which aluminum-containing adjuvants adsorb antigens and the effects of adsorption on antigen stability and immune response has become a mainstream research trend. Aluminum-containing adjuvants can enhance immune response through a variety of molecular pathways, but there are still significant challenges in designing effective immune-stimulating vaccine delivery systems with aluminum-containing adjuvants. At present, studies on the acting mechanism of aluminum-containing adjuvants mainly focus on aluminum hydroxide adjuvants. This review will take aluminum phosphate as a representative to discuss the immune stimulation mechanism of aluminum phosphate adjuvants and the differences between aluminum phosphate adjuvants and aluminum hydroxide adjuvants, as well as the research progress on the improvement of aluminum phosphate adjuvants (including the improvement of the adjuvant formula, nano-aluminum phosphate adjuvants and a first-grade composite adjuvant containing aluminum phosphate). Based on such related knowledge, determining optimal formulation to develop effective and safe aluminium-containing adjuvants for different vaccines will become more substantiated.

Safe and effective vaccines are still urgently needed to cope with the ongoing COVID-19 pandemic. Recently, we developed a recombinant COVID-19 vaccine (V-01) containing fusion protein (IFN-PADRE-RBD-Fc dimer) as antigen verified to induce protective immunity against SARS-CoV-2 challenge in pre-clinical study, which supported progression to Phase I clinical trials in humans. A Randomized, double-blind, placebo-controlled Phase I clinical trial was initiated at the Guangdong Provincial Center for Disease Control and Prevention (Gaozhou, China) in February 2021. Healthy adults aged between 18 and 59 years and over 60 years were sequentially enrolled and randomly allocated into three subgroups (1:1:1) either to receive the vaccine (10, 25, and 50 μg) or placebo (V-01: Placebo = 4:1) intramuscularly with a 21-day interval by a sentinel and dose escalation design. The data showed a promising safety profile with approximately 25% vaccine-related overall adverse events (AEs) within 30 days and no grade 3 or worse AEs. Besides, V-01 provoked rapid and strong immune responses, elicited substantially high-titre neutralizing antibodies and anti-RBD IgG peaked at day 35 or 49 after first dose, presented with encouraging immunogenicity at low dose (10 μg) subgroup and elderly participants, which showed great promise to be used as all-aged (18 and above) vaccine against COVID-19. Taken together, our preliminary findings indicate that V-01 is safe and well tolerated, capable of inducing rapid and strong immune responses, and warrants further testing in Phase II/III clinical trials.

One important feature of episodic memory is that it contains fine-grained and vividly recollected details. How to improve and maintain detailed information over time has been one of the central issues in memory research. Previous studies have inconsistent findings on whether detailed memory is forgotten more rapidly than gist memory. In this study, we investigated to what extent different encoding tasks modulated forgetting of gist and detailed information. In three experiments, participants were presented pictures of common objects and were asked to name them (Experiment 1), describe the details about them (Experiment 2) or imagine scenes associated with them (Experiment 3). After intervals of 10 minutes, one day, one week and one month, gist and detailed memories of the pictures were tested and assessed using a remember/know/guess judgement. The results showed that after the naming task, gist and detailed memories were forgotten at a similar rate, but after the description and the imagination tasks, detailed memory was forgotten at a slower rate than gist memory. The forgetting rate of gist memory was the slowest after the naming task, while that of detailed memory was the slowest after the description task. In addition, when three experiments were compared, the naming task enhanced the contributions of recollection and familiarity for gist memory, while the description task enhanced the contribution of familiarity for detailed memory. These results reveal the importance of the encoding task in the forgetting of gist and detailed information, and suggest a possible way to maintain perceptual details of objects at longer intervals.

Individuals fail to elicit protective antibody after hepatitis B vaccination remain at risk for hepatitis B virus infection. Analysis of the transcriptome of peripheral blood mononuclear cells (PBMCs) is essential to elucidate the characteristics of gene expression in non-responders. In this study, we enrolled seven responders who had received three injections and seven non-responders who had six injections of hepatitis B vaccine before. All the participants were then vaccinated with a three-dose boost regimen. Microarray analysis and Luminex assay were applied to examine mRNA expression and Th1/Th2/Th9/Th17/Th22/Treg cytokine and chemokine profiles in non-responders and responders. Differentially expressed genes in PBMCs of non-responders at 5 time points, i.e. pre-vaccination, 3rd, 7th, 28th day post the first dose vaccination and 7th day post the second dose vaccination indicated a dense network trend. Compared with responders, nine coding genes (BPI, DEFA1B, DEFA4, CEACAM8, MMP8, FOLR3, LTF, TCN1 and TKTL1) were significantly up-regulated in non-responders at all 5 time points, which could probably be the characteristic genes in hepatitis B vaccine non-responsiveness. Gene ontology analysis revealed that most of the DEGs were related with immune responses. Validation results of these 9 genes using quantitative real-time polymerase chain reaction were mostly consistent with the results of microarray. Cytokine analysis demonstrated that IL-27 and CXCL12 concentrations in responders were significantly higher than non-responders on the 3rd day after the first dose and 7th day after the second dose of vaccination, respectively. No significant difference was observed in other cytokine and chemokine signatures between the two groups. In conclusion, our results revealed characteristic transcriptome and cytokine changes in hepatitis B vaccine non-responders after boost immunization.

An HBsAg-HBIG therapeutic vaccine (Yeast-derived Immune Complexes, YIC) for chronic hepatitis B (CHB) patients has undergone a series of clinical trials. The HBeAg sero-conversion rate of YIC varied from 21.9% to 14% depending on the immunization protocols from 6 to 12 injections. To analyze the immunological mechanisms exerted by 6 injections of YIC, 44 CHB patients were separately immunized with YIC, alum as adjuvant control or normal saline as blank control, with add on of antiviral drug Adefovir in all groups. Kinetic increase in Th1 and Th2 cells CD4+ T cell sub-populations with association in decrease in Treg cells and increase of Tc1 and Tc17 cells in CD8+ T cells were observed in YIC immunized group. No such changes were found in the other groups. By multifunctional analysis of cytokine profiles, significant increase of IL-2 levels was observed, both in CD4+ and CD8+ T cells in the YIC immunized group, accompanied by increase in IFN-gamma and decrease of inhibitory factors (IL-10, TGF-β and Foxp3) in CD4+ T cells. In the alum immunized group, slight increase of IL-10, TGF-β and Foxp3 in CD4+ T cells was found after the second injection, but decreased after more injections, suggesting that alum induced early inflammatory responses to a certain extent. Similar patterns of responses of IL-17A and TNF-α in CD8+T cells were shown between YIC and the saline group. Results indicate that add on of Adefovir, did not affect host specific immune responses.

Japanese encephalitis virus (JEV) is a Flavivirus responsible for thousands of deaths every year for which there are no specific anti-virals. Here, Wang et al. report the cryo-EM structure of mature JEV at near-atomic resolution and identify structural elements that modulate stability and virulence.

Abstract Objectives Heterogeneity of clinical appearance had made it a challenge to make individualized and comprehensive management of perimenopause. This study aimed to estimate the profiles over heterogenous appearances of perimenopause with application of latent variable analysis methods over an optimized multidimensional assessing framework. Methods A two-phase clinical study was designed and advanced in the research center in Guangzhou, China. The assessing framework was developed over the initial item pool as integration of 4 scales including Insomnia severity index, Modified Kupperman index, Self-rating anxiety scale, and Self-rating depression scale. Validity and reliability of the instrument were evaluated and the psychometric properties of the items were estimated with multidimensional item response theory(MIRT). And then computer adaptive testing(CAT) was developed with the estimated model. We used latent profile analysis (LPA) to cluster patients into subgroups as patterns characterized by multidimensional latent trait scores. Finally, interpretability and efficiency were analyzed via comparison between the two assessing strategies. Result There were in total 336 patients diagnosed with perimenopause enrolled for the assessment. A conceptual framework was estimated consisting of 6 factors including sleep disturbance, mood swings, vasomotor symptoms, positive attitude towards life, multisystem abnormality, and fatigue. The construct validity was evaluated as optimized with CMIN/df = 1.814, GFI = 0.619, CFI = 0.721, TLI = 0.707 and RMSEA = 0.075. With scores in the simulated CAT, the 4 latent profiles model was estimated indicating the heterogeneity of perimenopause characterized by different severity of psychological and physical discomforts in the LPA. Conclusion The quantitative paradigm raised in this study revealed the potential patterns presenting heterogeneity of perimenopause offering better interpretation for clinical assessment.

COVID-19 has had a serious impact on the lives and health of people and severely affected the population flow in 2020. Baidu migration data offer great opportunities to study spatiotemporal interactions among cities. Revealing population flow patterns has important scientific significance for the precise prevention and control of the COVID-19 epidemic. The aim of this article is to reveal the spatiotemporal patterns of population flow and associated influential factors in 22 cities in the Sichuan-Chongqing region (SCR), which is regarded as the fourth pole of China’s economy. Four typical time periods are selected to study the spatiotemporal patterns of population flow. The regional population flow intensities in all cities and between different cities in the SCR are illustrated. Stepwise regression is used to analyse the factors affecting regional population flow intensity in four selected periods. The results show that (1) the COVID-19 epidemic greatly affected population flow in the SCR, (2) more travel occurred between cities on holidays than on weekdays in the SCR when the epidemic was not serious, and (3) the regional population flow intensity was strongly correlated with the population education level and transportation facilities when the epidemic was not serious.

Dark-field microscopy offers several advantages, including high image contrast, minimal cell damage, and the absence of photobleaching of nanoprobes, which make it highly advantageous for cell imaging. The NIR-II window has emerged as a prominent research focus in optical imaging in recent years, with its low autofluorescence background in biological samples and high imaging SBR. In this study, we initially compared dark-field imaging results of colorectal cancer cells in both visible and NIR-II wavelengths, confirming the superior performance of NIR-II imaging. Subsequently, we synthesized gold nanorods with localized surface plasmon resonance (LSPR) absorption peaks in the NIR-II window. After bio-compatible modification, we non-specifically labeled colorectal cancer cells for NIR-II dark-field scattering imaging. The imaging results revealed a sixfold increase in SBR, especially in the 1425–1475 nm wavelength range. Finally, we applied this imaging system to perform dark-field imaging of cell nuclei in the NIR-II region and used GNRs for specific nuclear labeling in colorectal cancer cells. The resulting images exhibited higher SBR than non-specifically-labeled cell imaging, and the probe’s labeling was precise, confirming the potential application of this system in photothermal therapy and drug delivery for cancer cells.

Fusarium graminearum is a destructive filamentous fungus, which widely exists in wheat and other cereal crops. Cysteine and Methionine are unique sulfur-containing amino acids that play an essential role in protein synthesis and cell life, but their functions and regulation in F. graminearum remain largely unknown. Here we identified two proteins, FgMet3 and FgMet14 in F. graminearum, which are related to the synthesis of cysteine and methionine. We found FgMet3 and FgMet14 were localized to the cytoplasm and there was an interaction between them. FgMet3 or FgMet14 deletion mutants (ΔFgMet3 and ΔFgMet14) were deficient in vegetative growth, pigment formation, sexual development, penetrability and pathogenicity. With exogenous addition of cysteine and methionine, the vegetative growth and penetrability could be completely restored in ΔFgMet3 and ΔFgMet14, while sexual reproduction could be fully restored in ΔFgMet3 and partially restored in ΔFgMet14. ΔFgMet3 and ΔFgMet14 exhibited decreased sensitivity to Congo red stress and increased sensitivity to SDS, NaCl, KCl, Sorbitol, Menadione, and Zn ion stresses. Moreover, FgMet3 and FgMet14 nonspecifically regulate the sensitivity of F. graminearum to fungicides. In conclusion, FgMet3 and FgMet14 interacted to jointly regulate the development, pathogenicity, pigment formation, sensitivity to fungicides and stress factors in F. graminearum.

Background: Hepatitis B vaccine is an effective measure to prevent hepatitis B virus infection. Whether chronic hepatitis C virus (HCV) infection decreases humoral and cell-mediated immunity responses to hepatitis B vaccination is still controversial.Methods: Patients with chronic HCV infection who were not in treatment and healthy controls, matched at a 1:2 ratio for community, sex, and age (within 5 years), were identified from a community-based screening. All participants received 3 doses of hepatitis B vaccine. Antibody to hepatitis B surface antigen was tested 1 month after the third vaccine dose and was compared between 2 groups. Spot-forming cells (SFCs) of interferon γ and interleukin 2, 4, 5, and 6 were counted by means of enzyme-linked immunospot, and SFC counts were compared between the 2 groups.Results: The rates of nonresponse and low, normal, and high response were 3.80%, 10.13%, 45.57%, and 40.50% respectively, in the HCV group, and the corresponding rates in the healthy control group were 1.26%, 10.13%, 39.24%, and 49.37% (all P > .05). There were no significant differences in SFC counts between the 2 groups for interferon γ or interleukin 2, 4, or 5 (all P > .05).Conclusions: This study provided preliminary evidence of the good immunogenicity and safety of hepatitis B vaccination among patients in China with chronic hepatitis C who are not in treatment.Clinical Trials Registration: NCT 02898922. [ABSTRACT FROM AUTHOR]

Modal-based acoustoelastic formulation is regarded as the cornerstone of vibro-acoustics and has been widely used for coupling analyses of structure-cavity systems. The controversy and the skepticism surrounding the acoustic velocity continuity with the surrounding vibrating structures have been persistent, calling for a systematic investigation and clarification. This fundamental issue of significant relevance is addressed in this paper. Through numerical analyses and comparisons with wave-based exact solution, an oscillating convergence pattern of the calculated acoustic velocity is revealed. Normalization of the results leads to a unified series truncation criterion allowing minimal prediction error, which is verified in three-dimensional cases. The paper establishes the fact that the modal based decomposition method definitely allows correct prediction of both the acoustic pressure and the velocity inside an acoustic cavity covered by a flexural structure upon using appropriate series truncation criteria. [ABSTRACT FROM AUTHOR]

Hepatitis A virus (HAV) infects ~1.4 million people annually and, although there is a vaccine, there are no licensed therapeutic drugs. HAV is unusually stable (making disinfection problematic) and little is known of how it enters cells and releases its RNA. Here we report a potent HAV-specific monoclonal antibody, R10, which neutralizes HAV infection by blocking attachment to the host cell. High-resolution cryo-EM structures of HAV full and empty particles and of the complex of HAV with R10 Fab reveal the atomic details of antibody binding and point to a receptor recognition site at the pentamer interface. These results, together with our observation that the R10 Fab destabilizes the capsid, suggest the use of a receptor mimic mechanism to neutralize virus infection, providing new opportunities for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Starting from December 2019, novel coronavirus disease 2019 (COVID-19) pandemic has caused tremendous economic loss and unprecedented health crisis across the globe. While the development of cure is at full speed, less attention and fewer effort have been spent on the prevention of this rapidly spreading respiratory infectious disease. Although so far, several vaccine candidates have advanced into clinical trials, limited data have been released regarding the vaccine efficacy and safety in human, not mention the long-term effectiveness of those vaccines remain as open question yet. Natural products and herbal medicines have been historically used for acute respiratory infection and generally show acceptable toxicity. The favorable stability for oral formulation and ease of scaling up manufacture make it ideal candidate for prophylactic. Hereby, we summarized the most recent advance in SARS-CoV-2 prevention including vaccine development as well as experimental prophylactics. Mainly, we reviewed the natural products showing inhibitory effect on human coronavirus, and discussed the herbal medicines lately used for COVID-19, especially focused on the herbal products already approved by regulatory agency with identifiable patent number. We demonstrated that to fill in the response gap between appropriate treatment and commercially available vaccine, repurposing natural products and herbal medicines as prophylactic will be a vigorous approach to stop or at least slow down SARS-CoV-2 transmission. In the interest of public health, this will lend health officials better control on the current pandemic.

Objective. To access the methodological and reporting quality of systematic reviews (SRs)/meta-analyses (MAs) about Chinese medical treatment for gastroesophageal reflux disease (GERD). Methods. The PubMed, Wanfang Data, China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP), Chinese Biomedical (CBM), Web of Science, and Cochrane Library databases were searched from inception to June 2020. Two researchers independently screened the literature considering the eligibility criteria. Overview Quality Assessment Questionnaire (OQAQ), Assessment of Multiple Systematic Reviews 2 (AMSTAR 2), and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to assess the methodological and reporting quality of the included reports. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to evaluate the level of evidence in each report. Results. Thirty-three SRs/MAs met the inclusion criteria. The OQAQ results showed that defects in the methodological quality of 17/32 reports were major, with scores of 3 points. Analyzing a single item as the object, search strategies (item 2), and risk of bias in individual studies (item 4) was considered poor. The AMSTAR 2 results showed that 25.4% of the items were not reported, and 7.8% of the items were only partially reported. The overall assessment of AMSTAR 2 showed the majority of systematic reviews and meta-analyses were of low/very low (31/33, 93.9%) methodological quality, with a lack of protocol registration and excluded study list. The PRISMA results showed that 19.9% of items were not reported, and 15.2% of items were only partially reported, due to a lack of protocol registration and study selection methods. The methodological and reporting quality of the included studies was generally poor. Evidence evaluation with GRADE showed that most (31/33) of the included studies had low or very low levels of evidence. Conclusion. The methodological and reporting quality of SRs/MAs about Chinese medical treatment for GERD is generally poor. The main problems included incomplete search strategies, risk of bias in individual studies, the lack of protocol registration and excluded study list, and incorrect study selection methods.

Background: Hepatitis B vaccine adjuvant, alum, is generally used for vaccination although it does not stimulate Th1 immunity and 10% of the population has low or no antibody response. Efforts have been continued to find more efficient vaccine adjuvants for better antibody response as well as stimulation of Th1 immunity. Methods: CpG DNA was used as an adjuvant for recombinant HBsAg to immunize 6- to 8-week-old female BALB/c mice with or without alum for different dosages. The production of HBsAb, CD80 and CD86 from dendritic cells, and cytokines IL-10, IL12, etc., were analyzed and compared for the performance of immunization. Results: 5-20 μg CpG DNA had the best co-stimulation effect of HBsAb serum conversion for mice vaccinated with recombinant expressed HBsAg. The mice vaccinated with recombinant 20 μg CpG DNA and regular vaccine (containing alum adjuvant) had the highest concentration of antibody production. IL-12b, IL-12a and IL10 mRNA reached to the peak level between 3 and 6 hours after the CpG DNA induction in splenocytes. The expression levels of CD80 and CD86 leucocyte surface molecules were increased with 20 μg CpG DNA alone or with 20 μg CpG DNA and 4 μg HBsAg. Conclusions: Our results confirmed the adjuvant effect of CpG DNA for HBsAg in the mouse model. The increase of IL10 and IL12 production suggested the involvement of Th1 cell activation. The activation of CD80 and CD86 molecules by CpG-ODN might be part of the mechanism of T/B cells coordination and the enhancement of recombinant HBsAg induced immune response. [ABSTRACT FROM AUTHOR]

Enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) are the primary causes of the epidemics of hand-foot-and-mouth disease (HFMD) that affect more than a million children in China each year and lead to hundreds of deaths. Although there has been progress with vaccines for EV71, the development of a CVA16 vaccine has proved more challenging, and the EV71 vaccine does not give useful cross-protection, despite the capsid proteins of the two viruses sharing about 80% sequence identity. The structural details of the expanded forms of the capsids, which possess nonnative antigenicity, are now well understood, but high resolution information for the native antigenic form of CVA16 has been missing. Here, we remedy this with high resolution X-ray structures of both mature and natural empty CVA16 particles and also of empty recombinant viruslike particles of CVA16 produced in insect cells, a potential vaccine antigen. All three structures are unexpanded native particles and antigenically identical. The recombinant particles have recruited a lipid moiety to stabilize the native antigenic state that is different from the one used in a natural virus infection. As expected, the mature CVA16 virus is similar to EV71; however, structural and immunogenic comparisons highlight differences that may have implications for vaccine production. [ABSTRACT FROM AUTHOR]