Neutralizing antibody levels associated with injectable and aerosolized Ad5-nCoV boosters and BA.2 infection.

BACKGROUND: Several COVID-19 vaccines are in widespread use in China. Few data exist on comparative immunogenicity of different COVID-19 vaccines given as booster doses. We aimed to assess neutralizing antibody levels raised by injectable and inhaled aerosolized recombinant adenovirus type 5 (Ad5)-vectored COVID-19 vaccine as a heterologous booster after an inactivated COVID-19 vaccine two-dose primary series. METHODS: Using an open-label prospective cohort design, we recruited 136 individuals who had received inactivated vaccine primary series followed by either injectable or inhaled Ad5-vectored vaccine and measured neutralizing antibody titers against ancestral SARS-CoV-2 virus and Omicron BA.1 and BA.5 variants. We also measured neutralizing antibody levels in convalescent sera from 39 patients who recovered from Omicron BA.2 infection. RESULTS: Six months after primary series vaccination, neutralizing immunity against ancestral SARS-CoV-2 was low and neutralizing immunity against Omicron (B.1.1.529) was lower. Boosting with Ad5-vectored vaccines induced a high immune response against ancestral SARS-CoV-2. Neutralizing responses against Omicron BA.5 were ≥ 80% lower than against ancestral SARS-CoV-2 in sera from prime-boost subjects and in convalescent sera from survivors of Omicron BA.2 infection. Inhaled aerosolized Ad5-vectored vaccine was associated with greater neutralizing titers than injectable Ad5-vectored vaccine against ancestral and Omicron SARS-CoV-2 variants. CONCLUSIONS: These findings support the current strategy of heterologous boosting with injectable or inhaled Ad5-vectored SARS-CoV-2 vaccination of individuals primed with inactivated COVID-19 vaccine.

Beyond Vaccination Rates: A Synthetic Random Proxy Metric of Total SARS-CoV-2 Immunity Seroprevalence in the Community.

BACKGROUND: Explicit knowledge of total community-level immune seroprevalence is critical to developing policies to mitigate the social and clinical impact of SARS-CoV-2. Publicly available vaccination data are frequently cited as a proxy for population immunity, but this metric ignores the effects of naturally acquired immunity, which varies broadly throughout the country and world. Without broad or random sampling of the population, accurate measurement of persistent immunity post-natural infection is generally unavailable. METHODS: To enable tracking of both naturally acquired and vaccine-induced immunity, we set up a synthetic random proxy based on routine hospital testing for estimating total immunoglobulin G (IgG) prevalence in the sampled community. Our approach analyzed viral IgG testing data of asymptomatic patients who presented for elective procedures within a hospital system. We applied multilevel regression and poststratification to adjust for demographic and geographic discrepancies between the sample and the community population. We then applied state-based vaccination data to categorize immune status as driven by natural infection or by vaccine. RESULTS: We validated the model using verified clinical metrics of viral and symptomatic disease incidence to show the expected biologic correlation of these entities with the timing, rate, and magnitude of seroprevalence. In mid-July 2021, the estimated immunity level was 74% with the administered vaccination rate of 45% in the two counties. CONCLUSIONS: Our metric improves real-time understanding of immunity to COVID-19 as it evolves and the coordination of policy responses to the disease, toward an inexpensive and easily operational surveillance system that transcends the limits of vaccination datasets alone.

Routine Hospital-based SARS-CoV-2 Testing Outperforms State-based Data in Predicting Clinical Burden.

Throughout the coronavirus disease 2019 (COVID-19) pandemic, government policy and healthcare implementation responses have been guided by reported positivity rates and counts of positive cases in the community. The selection bias of these data calls into question their validity as measures of the actual viral incidence in the community and as predictors of clinical burden. In the absence of any successful public or academic campaign for comprehensive or random testing, we have developed a proxy method for synthetic random sampling, based on viral RNA testing of patients who present for elective procedures within a hospital system. We present here an approach under multilevel regression and poststratification to collecting and analyzing data on viral exposure among patients in a hospital system and performing statistical adjustment that has been made publicly available to estimate true viral incidence and trends in the community. We apply our approach to tracking viral behavior in a mixed urban-suburban-rural setting in Indiana. This method can be easily implemented in a wide variety of hospital settings. Finally, we provide evidence that this model predicts the clinical burden of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) earlier and more accurately than currently accepted metrics. See video abstract at, http://links.lww.com/EDE/B859.

Effectiveness and Safety of an Inactivated Enterovirus 71 Vaccine in Children Aged 6-71 Months in a Phase IV Study.

BACKGROUND: Evaluation of a licensed inactivated enterovirus type 71 (EV71) vaccine is needed in a phase IV study with a large population to identify its effectiveness and safety for further application. METHODS: An open-label, controlled trial involving a large population of 155 995 children aged 6-71 months was performed; 40 724 were enrolled in the vaccine group and received 2 doses of inactivated EV71 vaccine at an interval of 1 month, and the remaining children were used as the control group. The EV71-infected cases with hand, foot, and mouth disease were monitored in the vaccine and control groups during a follow-up period of 14 months since the 28th day postinoculation through the local database of the Notifiable Infectious Diseases Network. The effectiveness of the vaccine was estimated by comparing the incidence density in the vaccine group versus that in the control group based upon EV71-infected patients identified via laboratory testing. In parallel, the active and passive surveillance for safety of the vaccine was conducted by home or telephone visits and by using the Adverse Event Following Immunization (AEFI) system, respectively. RESULTS: An overall level of 89.7% (95% confidence interval, 24.0-98.6%) vaccine effectiveness against EV71 infection and a 4.58% rate of reported adverse events were observed. Passive surveillance demonstrated a 0.31% rate of reported common minor reactions. CONCLUSIONS: The clinical protection and safety of the EV71 vaccine were demonstrated in the immunization of a large population. CLINICAL TRIALS REGISTRATION: NCT03001986.

Liver function biomarkers disorder is associated with exposure to perfluoroalkyl acids in adults: Isomers of C8 Health Project in China.

Exposure to chemicals may affect liver enzyme to increase the risk of liver diseases. Perfluoroalkyl acids (PFAAs) are one kind of persistent organic pollutants with hepatotoxic effect in organism. However, data is scarce to characterize the hepatotoxic effects of specific structural PFAA isomers in general population. To address this data gap, we evaluated the association between serum PFAAs concentration and liver function biomarkers in the Isomers of C8 Health Project in China. High performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used to measure 18 serum PFAAs, except for linear and branched isomers of PFOA/PFOS, nine perfluorinated carboxylic acids (PFCAs) and two perfluorinated sulfonic acids (PFSAs) were also included, in 1605 adult residents of Shenyang, China. Values for nine serum liver function biomarkers were determined by full-automatic blood biochemical analyzer. Linear regression was used to evaluate associations between PFAAs and continuous liver function biomarkers and logistic regression to assess markers dichotomized per clinical reference intervals. Results indicated that serum PFAAs concentrations were associated with liver biomarker levels suggestive of hepatotoxicity, especially for liver cell injury. For example, a 1 ln-unit increase in total- perfluorooctanoic acid (PFOA) exposure was associated with a 7.4% [95% confidence interval (CI): 3.9%, 11.0%] higher alanine aminotransferase (ALT) level in serum. Interestingly, we observed association between branched PFAA isomers and liver biomarkers. For example, one ln-unit increase in branched perfluorooctane sulfonate (PFOS) isomers exposure was associated with a 4.3% increase in ALT level (95% CI: 1.2%, 7.4%) and a 33.0% increased odds of having abnormal ALT (95% CI: 5.0%, 67.0%). Also, we found that PFNA had positive association with ALT [(6.2%, 95% CI: 3.1%, 9.4%) and AST levels (2.5%, 95% CI: 0.5%, 4.5%)]. Logistic regression results showed that PFPeA, PFHxA, PFNA, PFDoDA, PFTrDA and PFTeDA had statistically association with abnormal prealbumin. Conclusively, our results support previous studies showing association between PFAAs exposure and liver function biomarkers. We found new evidence that branched PFAAs isomer exposure is associated with the risk of clinically relevant hepatocellular dysfunction.

Ambient PM1 air pollution, blood pressure, and hypertension: Insights from the 33 Communities Chinese Health Study.

No evidence exists concerning the association between blood pressure and ambient particles with aerodynamic diameter ≤ 1.0 µm (PM1), a major component of PM2.5 (≤ 2.5 µm) particles, and potentially causing more hazardous health effects than PM2.5. We aimed to examine the associations of blood pressure in adults with both PM1 and PM2.5 in China. In 2009, we randomly selected 24,845 participants aged 18-74 years from 33 communities in China. Using a standardized mercuric-column sphygmomanometer, we measured blood pressure. Long-term exposure (2006-08) to PM1 and PM2.5 were estimated using a spatial statistical model. Generalized linear mixed models were used to evaluate the associations between air pollutants and blood pressure and hypertension prevalence, controlling for multiple covariates. A 10-µg/m3 increase in PM1 was significantly associated with an increase of 0.57 (95% CI 0.31-0.83) mmHg in systolic blood pressure (SBP), 0.19 (95% CI 0.03-0.35) mmHg increase in diastolic blood pressure (DBP), and a 5% (OR=1.05; 95% CI 1.01-1.10) increase in odds for hypertension. Similar associations were detected for PM2.5. Furthermore, PM1-2.5 showed no association with blood pressure or hypertension. In summary, both PM1 and PM2.5 exposures were associated with elevated blood pressure levels and hypertension prevalence in Chinese adults. In addition, most of the pro-hypertensive effects of PM2.5 may come from PM1. Further longitudinal designed studies are warranted to validate our findings.

Long-term exposure to ambient air pollution (including PM1) and metabolic syndrome: The 33 Communities Chinese Health Study (33CCHS).

Little evidence exists about the effects of long-term exposure to ambient air pollution on metabolic syndrome (MetS). This study aimed to determine the association between long-term ambient air pollution and MetS in China. A total of 15,477 adults who participated in the 33 Communities Chinese Health Study (33CCHS) in 2009 were evaluated. MetS was defined based on the recommendation by the Joint Interim Societies. Exposure to air pollutants was assessed using data from monitoring stations and a spatial statistical model (including particles with diameters ≤ 1.0 µm (PM1), ≤ 2.5 µm (PM2.5), and ≤ 10 µm (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), and ozone (O3)). Two-level logistic regression analyses were utilized to assess the associations between air pollutants and MetS. The prevalence of MetS was 30.37%. The adjusted odds ratio of MetS per 10 µg/m3 increase in PM1, PM2.5, PM10, SO2, NO2, and O3 were 1.12 (95% CI = 1.00-1.24), 1.09 (95% CI = 1.00-1.18), 1.13 (95% CI = 1.08-1.19), 1.10 (95% CI = 1.02-1.18), 1.33 (95% CI = 1.12-1.57), and 1.10 (95% CI = 1.01-1.18), respectively. Stratified analyses indicated that the above associations were stronger in participants with the demographic variables of males, < 50 years of age, and higher income, as well as with the behavioral characteristics of smoking, drinking, and consuming sugar-sweetened soft drinks frequently. This study indicates that long-term exposure to ambient air pollutants may increase the risk of MetS, especially among males, the young to middle aged, those of low income, and those with unhealthy lifestyles.

Occurrence, vertical distribution and transport of organic amine pesticides in the seawater from the East China Sea and the South China Sea.

Organic amine pesticides (OAPs) are widely used as insecticides, fungicides and herbicides in agricultural production. China is a large agricultural country, and the sprayed pesticides may impact the fragile marine environment through surface runoff. This study revealed the pollution characteristics of thirty-three OAPs in the East China Sea (ECS) and the South China Sea (SCS) and investigated their vertical variations in water columns. The ∑OAPs ranged from below method detection limits to 3.4 ng/ L, with an average value of 0.93 ng/ L. Diphenylamine and beflubutamid were the two most abundant compounds, contributing 64 % and 14 % of the ∑OAPs, respectively. The ∑OAPs in the ECS were significantly (M-W U test, p < 0.01) higher than that in the SCS, and OAPs exhibited different composition profiles. Diphenylamine was the most abundant compound in the ECS, while beflubutamid was dominant in the SCS, which may be related to industrial production (such as rubber synthesis) and agricultural activities. In the water columns, OAPs concentrations were higher in deep layers compared to that in surface seawater, which may be due to weak light and low temperature reducing the degradation of pesticides, indicating the deep ocean is a sink for OAPs. Under the dilution of seawater, the concentrations of OAPs decreased from the Pearl River Estuary to the open sea, and the South China Sea Warm Current also caused the decrease of OAPs from south to north. A preliminary risk assessment indicated that OAPs in the water pose no significant risk to aquatic organisms.

Occurrence, partitioning and transport of perfluoroalkyl acids in gas and particles from the southeast coastal and mountainous areas of China.

Perfluoroalkyl acids (PFAA) in gas and particles were analyzed in southeast coastal and mountainous cities, including Fuzhou, Xiamen, Zhangzhou and Nanping, to study the pollution characteristics, particle size distribution, phase partitioning and atmospheric transport. PFAA ranged from 7.8 to 290 pg m-3 in gaseous phase, 27 - 1200 pg m-3 in particulate phase, and perfluorobutanoic acid (PFBA), perfluorooctanoic acid (PFOA) were main compounds. PFAA had the highest concentration in Nanping with perfluorohexanoic acid (PFHxA) dominant, which could be related to the emission of PFAS from local industrial plants. Perfluorocarboxylic acids (PFCAs) and perfluoroalkyl sulfonic acids (PFSAs) exhibited different particle size distribution characteristics, with PFSAs preferring to distribute on coarse particles, which could be affected by the salt, minerals and organic matter in different particle sizes. The gas - particle partitioning coefficient (KPA) had a line relationship with the fluorinated carbon chain length of PFAA, suggesting that long-chain PFAA tended to exist in particulate phase. The Winter Monsoon could transport to the study area and drive atmospheric PFAS to southern cities. HIGHLIGHTS: • Industrial plants contributed high concentrations of PFAA. • PFSAs tended to present in coarse particles. • Log KPA increased linearly with increasing carbon chain length of PFAA. • Winter Monsoon drove atmospheric PFAA to southern cities.

Occurrence, partitioning behavior and risk assessments of per- and polyfluoroalkyl substances in water, sediment and biota from the Dongshan Bay, China.

Twenty-five per- and polyfluoroalkyl substances (PFASs) were analyzed in water, sediment and biota from the Dongshan Bay (DSB) to study their seasonal variations, composition profiles, potential pollution sources, partitioning behavior and risk assessments. The total concentrations of PFASs (∑PFASs) in water ranged from 3.2 to 6.5 ng L-1 (mean 4.0 ng L-1) during the dry season, and 0.11-4.5 ng L-1 (mean 1.3 ng L-1) during the wet season. Perfluoro-butane sulfonic acid (PFBS), perfluoro-butanoic acid (PFBA) and perfluoro-octanoic acid (PFOA) were dominated and frequently detected in water. ∑PFASs in sediment were 0.15-0.37 ng g-1 dw (mean 0.24 ng g-1 dw) with the long-chain PFASs perfluoro-octane sulfonic acid (PFOS) dominating. High concentrations of PFASs in land-based drainage outlets (2.0-384.6 ng L-1 in water) and Zhangjiang estuary indicated that land-based discharges and the river discharge were the main sources. High concentration (366.1 ng L-1) and proportion (94%) of PFBA on one drainage outlet agreed with the trend that PFBA was as an alternative to long-chain PFASs. ∑PFASs in biota ranged from 0.11 to 0.40 ng g-1 ww, and only long-chain PFASs were detected. The partition coefficients (log Kd) of PFASs between water and sediment ranged from 1.13 to 2.90, increased with carbon chain length, implied long-chain PFASs are more likely to adsorb to sediment. Results of ecological and health risk assessments indicated that PFASs had no significant risk for the aquatic organisms and local residents.

Perfluoroalkyl substances in water, sediment, and fish from a subtropical river of China: Environmental behaviors and potential risk.

Perfluoroalkyl substances (PFAS) in water, sediment and fish were analyzed from a subtropical river, Jiulong River in the southeast of China, to character the sources, seasonal variations, bioconcentration and potential risk. PFAS in water, sediment, muscle and liver tissues of fish ranged from 2.5 to 410 ng L-1, 0.24-1.9 ng g-1 dw, 25-100 and 35-1100 ng g-1 ww, respectively. Generally, perfluorohexanoic acid (PFHxA) was the dominant compound in water, while, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) were the dominant compounds in sediment and fish tissues. High concentrations of PFAS in water were found near the machinery manufacturing and paper packaging plants in the north branch of Jiulong River. PFAS during the dry season were significantly (P < 0.01) higher than that during the normal season and wet season. The Kd of PFAS increased with the carbon chain length, and perfluoroalkyl sulfonic acids (PFSAs) exhibited higher Kd values than perfluoroalkyl carboxylic acids (PFCAs), indicating these long chain PFAS tended to be adsorbed by sediment. Long chain PFAS exhibited high bioconcentration factors (BCFs), while short and medium carbon chain PFAS had weak bioconcentration capacity. The hazard ratios (HR) suggested that frequent consumption of river fish may pose health risks to local population.

Neutral and ionizable per-and polyfluoroalkyl substances in the urban atmosphere: Occurrence, sources and transport.

In the atmosphere, the photodegradation of neutral per-and polyfluoroalkyl substances (n-PFASs) is a source of ionizable PFASs (i-PFASs). However, they are not frequently simultaneously analyzed to study their transport and sources. In this study, n-PFASs and i-PFASs were simultaneously analyzed in the atmosphere of China, Japan and Malaysia to investigate the occurrence, seasonal variations, sources and transport. Results showed that n-PFASs ranged from 4.8 to 1400 pg m-3, with an average value of 170 pg m-3, and 8:2 fluorotelomer alcohol (8:2 FTOH) was the most abundant compound. i-PFASs ranged from 3.7 to 330 pg m-3, with an average value of 49 pg m-3, and perfluorobutanoic acid (PFBA) had the highest concentration. Generally, airborne PFASs had a decreasing gradient from cities with high population density toward less industrialized sites. i-PFASs exhibited significantly (P < 0.05) seasonal variations, which were higher in the summer. 8:2 FTOH and 10:2 FTOH had significant (P < 0.05) positive correlations with perfluorooctanoic acid and perfluorodecanoic acid, suggesting that they had same sources, such as co-emission and photodegradation of FTOHs. Urumqi and Selangor were far away from industry, and high percentages (>95%) but low concentrations of PFBA were found in these cities, indicating the long-range atmospheric transport of PFBA due to its high volatility. The Summer Monsoon may promote the transport of high concentrations of PFAS from coastal cities to inland cities.

Particle size distribution, wet deposition and scavenging effect of per- and polyfluoroalkyl substances (PFASs) in the atmosphere from a subtropical city of China.

Per- and polyfluoroalkyl substances (PFASs) as emerging organic pollutants have received great attention, but the scavenging efficiency of particulate PFASs by wet deposition was rarely studied. For the first time, we reported the scavenging efficiency of PFASs on different particle sizes. In this study, both rainwater and particle samples were collected for a whole year from Xiamen, a subtropical city of China. Particulate PFASs ranged from 4.11 to 67.41 pg m-3, with an average value of 26.56 pg m-3, and perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA) were the main compounds. Perfluorocarboxylic acids (PFCAs) were predominantly observed on fine particles (<1 µm), while PFOS and 6:2 chlorinated polyfluoroalkyl ether sulfonic acid (6:2 Cl-PFESA) had large proportions on coarse particles (1-2.5 µm and 2.5-10 µm). In the rainwater, PFASs ranged from 0.20 to 180.65 ng L-1, with an average value of 10.71 ng L-1, and perfluorobutanoic acid (PFBA), PFOA were the main compounds. The wet deposition flux of ∑PFASs was 5200 mg km-2 yr-1, exhibiting high fluxes during the wet season (March to September). The scavenging efficiency of particulate PFOS and PFOA ranged from 68%-98% during the rainfall, and wash-out of the raindrops was found to be one of the main scavenging mechanisms. In addition, the precipitation duration and intensity influenced the scavenging efficiency. The scavenging capacity of PFCAs was large on fine particles, while for per-and polyfluoroalkyl sulfonic acids, the scavenging capacity was high on coarse particles. Our results showed that wet deposition effectively removed medium to long carbon chain (≥C6) PFASs in the atmosphere.

[Environmental Process, Effects and Risks of Emerging Contaminants in the Estuary-Coastal Environment].

Human activities and global climate change have contributed substantially to the input of land-sourced pollutants into the aquatic environment, especially for emerging or newly identified contaminants, such as microplastics, emerging persistent organic pollutants, pharmaceuticals, and personal care products. The prevalence and toxicity of these emerging pollutants has raised continued concern for the health and safety of the public worldwide. A review of sources, distribution, interfacial transport processes of microplastics, per-and polyfluorinated compounds, antibiotics, and endocrine-disrupting chemicals and factors that influence their environmental behavior in the estuary-coastal environment have been included. The adverse ecological effects and health risks of these emerging contaminants to humans were also reviewed. Lastly, the direction of future research was provided regarding the environmental behavior of multiple emerging pollutants in the coastal environment and the health risks resulting from their interactions, supporting the prevention and control of marine pollution and the healthy development of the marine economy.

Legacy and emerging persistent organic pollutants in the marginal seas of China: Occurrence and phase partitioning.

Emerging per-and polyfluoroalkyl substances (PFASs) and traditional organochlorine pesticides (OCPs), polycyclic aromatic hydrocarbons (PAHs) in the marginal seas of China were analyzed to study the occurrence, transport and phase partitioning. The influence of organic carbon (OC) and element carbon (EC) on particulate emerging pollutants in seawater was studied for the first time. The concentrations of PFASs, OCPs and PAHs in the seawater (dissolved phase plus particulate phase) ranged from 1.4 to 8.6, 0.76 to 4.3 and 8.4 to 130 ng L-1, respectively. Pollutants in the northern East China Sea were generally higher than that in the southern East China Sea and South China Sea, which may be attribute to river discharges and land sources in the Yangtze River Delta. The Yellow Sea Coastal Current and Yangtze River Dilute Water drove the transport of contaminants from north to south marginal seas. Positive correlations between EC and PAHs were found, which can be explained by co-emission of them during combustion. Moreover, positive correlations between OC, EC and Log Kd for BkF, BeP, HCB, 6:2 FTSA were found, which demonstrated that OC and EC promoted the partitioning of these high oleophilic compounds to suspended particle.

Vertical distribution and river-sea transport of microplastics with tidal fluctuation in a subtropical estuary, China.

The river-sea transport of microplastic with complex environmental conditions and diverse driving factors has received growing attention in the estuary. This research investigated the vertical distribution of microplastics in the water column and surface sediments and explored the effect of tidal variation on the transport of microplastics in Jiulong Estuary and Xiamen Bay, China. Results show that the microplastics in the estuary (630 ± 515 µm) was significantly larger than that in the bay (344 ± 420 µm, p < 0.01). Low-density microplastics are present in the whole water column, while high-density microplastics was apt to accumulate in the bottom water and surface sediment suggesting biofouling and material density of microplastics synergistic affect its vertical distribution. Every 1-2 h high-frequency samples collected in a whole tide found the increase of fine size (45-300 µm) and decrease of large size (>300 µm) in the flood tide, which implied fine microplastics were easily driven into the estuary from the bay at flood tide than large microplastics. The abundance of microplastics in the sediments decreased in the fast-rising and fast-falling period implies the tide influences the fragmentation and resuspension of microplastics in the estuary. Finally, the flux of microplastics entering Xiamen Bay was 53.5 t/month in the moderate flow month were estimated based on the abundance of different water layers instead of floating microplastics in the surface water.

KAP1 Positively Modulates Influenza A Virus Replication by Interacting with PB2 and NS1 Proteins in Human Lung Epithelial Cells.

Influenza virus only encodes a dozen of viral proteins, which need to use host machinery to complete the viral life cycle. Previously, KAP1 was identified as one host protein that potentially interacts with influenza viral proteins in HEK 293 cells. However, the role of KAP1 in influenza virus replication in human lung alveolar epithelial cells and the underlying mechanism remains unclear. In this study, we first generated KAP1 KO A549 cells by CRISPR/Cas9 gene editing. KAP1 deletion had no significant effect on the cell viability and lack of KAP1 expression significantly reduced the influenza A virus replication. Moreover, we demonstrated that KAP1 is involved in the influenza virus entry, transcription/replication of viral genome, and viral protein synthesis in human lung epithelial cells and confirmed that KAP1 interacted with PB2 and NS1 viral proteins during the virus infection. Further study showed that KAP1 inhibited the production of type I IFN and overexpression of KAP1 significantly reduced the IFN-ß production. In addition, influenza virus infection induces the deSUMOylation and enhanced phosphorylation of KAP1. Our results suggested that KAP1 is required for the replication of influenza A virus and mediates the replication of influenza A virus by facilitating viral infectivity and synthesis of viral proteins, enhancing viral polymerase activity, and inhibiting the type I IFN production.

A Glycolipid α-GalCer Derivative, 7DW8-5 as a Novel Mucosal Adjuvant for the Split Inactivated Influenza Vaccine.

Influenza virus infects the host and transmits through the respiratory tract (i.e., the mouth and nose); therefore, the development of intranasal influenza vaccines that mimic the natural infection, coupled with an efficient mucosal adjuvant, is an attractive alternative to current parenteral vaccines. However, with the withdrawal of cholera toxin and Escherichia coli heat-labile endotoxin from clinical use due to side effects, there are no approved adjuvants for intranasal vaccines. Therefore, safe and effective mucosal adjuvants are urgently needed. Previously, we reported that one derivative of α-Galactosylceramide (α-GalCer), 7DW8-5, could enhance the protective efficacy of split influenza vaccine by injection administration. However, the mucosal adjuvanticity of 7DW8-5 is still unclear. In this study, we found that 7DW8-5 promotes the production of secret IgA antibodies and IgG antibodies and enhances the protective efficacy of the split influenza vaccine by intranasal administration. Furthermore, co-administration of 7DW8-5 with the split influenza vaccine significantly reduces the virus shedding in the upper and lower respiratory tract after lethal challenge. Our results demonstrate that 7DW8-5 is a novel mucosal adjuvant for the split influenza vaccine.

Safety, immunogenicity, and immune persistence of two inactivated COVID-19 vaccines replacement vaccination in China: An observational cohort study.

BACKGROUND: To mitigate a national shortage of WIBP-CorV COVID-19 vaccine, China's regulator approved administering BBIBP-CorV after WIBP-CorV for completion of a primary series. In a pragmatic observational study, we compared immunogenicity and safety of a primary series of WIBP-CorV followed by BBIBP-CorV with a primary series of two doses of BBIBP-CorV. METHODS: We invited healthy 18-59-years-old adults who had already received either WIBP-CorV or BBIBP-CorV as their first dose in a primary series to participate in this observational cohort study. Subjects who had received WIBP-CorV as their first dose became the observation group; subjects who had received BBIBP-CorV as their first dose became the control group. All participants received BBIBP-CorV as their second dose. We obtained sera 1, 2, and 6 months after second doses for nAb titer measurement by micro-neutralization cytopathic effect assay with SARS-CoV-2 strain HB01, standardized with WHO International Standard for anti-SARS-CoV-2 immunoglobulin. Safety was assessed for the 7 days after administration of second doses. RESULTS: Between March and December 2021, 275 subjects were included in the observation group and 133 in the control group. Neutralizing seropositivity (≥1:4) rates were 98.91 % and 99.25 % at 1 month and 53.16 % and 70.69 % at 6 months. One-month geometric mean titers (GMTs) were 21.33 and 22.45; one-month geometric mean concentrations (GMCs) were 227.71 IU/mL and 273.27 IU/mL. One to two months after vaccination, observation group seropositivity rates and titers were not significantly different to the control group's. Adverse reaction rates were 11.27 % and 18.80 %, all mild or moderate in severity. CONCLUSIONS: Both primary series were immunogenic; immunogenicity of WIBP-CorV followed by BBIBP-CorV was not different than immunogenicity following two doses of BBIBP-CorV for two months after vaccination; safety profiles were acceptable for both regimens. BBIBP-CorV can be used to complete a primary series that started with WIBP-CorV.

Transcriptomic Analysis of the Effect of GAT-2 Deficiency on Differentiation of Mice Naïve T Cells Into Th1 Cells In Vitro.

The neurotransmitter γ-aminobutyric acid (GABA) is known to affect the activation and function of immune cells. This study investigated the role of GABA transporter (GAT)-2 in the differentiation of type 1 helper T (Th1) cells. Naïve CD4+ T cells isolated from splenocytes of GAT-2 knockout (KO) and wild-type (WT) mice were cultured; Th1 cell differentiation was induced and transcriptome and bioinformatics analyses were carried out. We found that GAT-2 deficiency promoted the differentiation of naïve T cells into Th1 cells. RNA sequencing revealed 2984 differentially expressed genes including 1616 that were up-regulated and 1368 that were down-regulated in GAT-2 KO cells compared to WT cells, which were associated with 950 enriched Gene Ontology terms and 33 enriched Kyoto Encyclopedia of Genes and Genomes pathways. Notably, 4 signal transduction pathways (hypoxia-inducible factor [HIF]-1, Hippo, phospholipase D, and Janus kinase [JAK]/signal transducer and activator of transcription [STAT]) and one metabolic pathway (glycolysis/gluconeogenesis) were significantly enriched by GAT-2 deficiency, suggesting that these pathways mediate the effect of GABA on T cell differentiation. Our results provide evidence for the immunomodulatory function of GABA signaling in T cell-mediated immunity and can guide future studies on the etiology and management of autoimmune diseases.