Dengue has been prevalent in Guangdong Province, China, for more than forty years and has shown an increasing trend over the past decade. A fine-scale analysis of dengue clusters was conducted. The relationship between virus evolution time and spatial distance was analyzed, and a genetic algorithm was used to quantify the effects of environmental, social, and economic factors on the transmission of dengue. A retrospective study analyzed 172 confirmed dengue cases (April 2019 to April 2020) at the Seventh Affiliated Hospital of Southern Medical University. Whole-genome sequencing revealed a unique transmission origin in Lishui town, Guangdong Province (99.64

Background Serological surveillance of rubella antibodies is favorable for disease risk assessment and evaluation of vaccination effectiveness, and understanding the immunity status of healthy individuals. Methods From 2021 to 2023, serum samples were collected from healthy residents in Guangzhou and Heyuan of Guangdong Province, China. Rubella IgG antibody levels were determined by enzyme-linked immunosorbent assay (ELISA) and analyzed in combination with vaccination history. Results In this study, a total of 5,092 participants were enrolled, and the positivity rate of rubella IgG antibodies is 84.58% (95% CI: 83.56%-85.56%). The geometric mean concentration (GMC) was 37.45 IU/mL (95% CI: 36.34–38.57). The seropositivity rate and concentration of rubella antibody exhibited a U-shaped curve across age groups. The highest rates were observed in the 8 months − 3 years group (98.21%) and the > 60 years group (92.57%), while the lowest seropositivity rate was found in the 17–25 years group (67.17%). The seropositivity rate in the 2 doses vaccinated group (93.78%) was significantly higher than both the unvaccinated group (82.50%) and the 1 dose vaccinated group (78.67%). Based on the Generalized Additive Model (GAM) prediction, the antibody of 2 doses vaccination group showed an annual decline rate of 5.6%, with predicted persistence for 32.6 years. Conclusions The rubella IgG antibody among healthy populations in Guangdong Province during 2021–2023 remained at a high level. The 2 doses Measles-mumps-rubella combined vaccine (MMR) vaccination could stimulate long-lasting antibody protection. However, lower antibody levels in populations born before China’s NIP implementation, particularly among 17–40 years, suggest an booster vaccination.

ABSTRACT To establish a laboratory detection assay for a human neutralizing antibody (NAb) against rabies virus and to evaluate its efficiency in human serum samples. A pseudovirus pXN2‑RABV‑G harboring the RABV G gene was applied. The precision, robustness, linearity, stability, inclusivity, and limit of detection of the assay were evaluated. The consistency and correlation of the assay with ELISA and rapid fluorescent focus inhibition test (RFFIT) were analyzed. A pseudovirus-based neutralizing antibody (pVNA) detection system based on the pXN2‑RABV‑G was successfully developed and showed broad robustness (culture media: χ 2 = 4.00, P > 0.05, cell passages: χ 2 = 0.25, P > 0.05), precision (independent detection: P > 0.05), lower/upper limit of linearity (0.09 to 93.73 IU/mL, R 2 > 0.95), and stability ( P > 0.05). The limit of detection (LOD) was 2.63 IU/mL (95% CI: 1.81–3.84), expressed as the lowest human sera antibody level reliably distinguishable from background signals, and the coefficient of variation was less than 20%. Compared with the commercial ELISA and the gold standard RFFIT assay, the kappa values were 0.74 and 0.82, respectively, and the results were highly consistent. Linear correlation analysis revealed a strong correlation between these variables ( R 2 > 0.90). A total of 103 recipients from 2019 to 2023 were included in the serological testing and the following analysis. NAb titers were significantly correlated with vaccine dose ( P < 0.001) and the most recent vaccination time ( P < 0.001). The geometric mean titer (GMT) of the 5-dose vaccination group was greater than that of the 1-dose, 2-dose, 3-dose, and 4-dose groups (3.15 vs 3.19 vs 6.18 vs 12.21 vs 13.40 IU/mL). The established pVNA assay for human rabies NAb detection has a detection capability similar to that of the gold standard RFFIT, but it has the advantages of reduced biosafety requirements, laboratory activity, and time, which highlight its safety, high efficiency, and feasibility for screening and monitoring rabies virus antibodies after vaccination. IMPORTANCE Rabies is a lethal disease with no effective clinical treatment. Vaccination is the only way to prevent it routinely, which makes post-vaccination antibody testing essential. The current standard test requires a highly equipped laboratory, biosafety measures, and is time-consuming. This study develops a safe, efficient test for detecting rabies neutralizing antibodies using pseudovirus technology. It is comparable to the gold standard test in accuracy but easier to implement in routine labs, which enables broader use in screening and monitoring antibodies post-vaccination. This advantage addresses a key gap in rabies prevention, reducing the uncertainty for individuals with immunodeficiency who are nonresponsive to vaccination and at risk of rabies exposure.

IntroductionSARS-CoV-2 undergoes persistent genomic evolution, yet prevalent circulating variants tend to evolve toward reduced pathogenicity. However, direct comparative pathogenesis data involving contemporary, immune-evasive strains—such as the Omicron EG.5 subvariant (a descendant of the globally dominant XBB lineage)—relative to ancestral strains remain scarce.MethodsTo clarify the evolutionary trajectory of viral virulence, we conducted a systematic, head-to-head comparison of the in vivo pathogenicity of three pivotal strains: the ancestral Wild-type (Wuhan lineage), Delta, and the currently circulating Omicron EG.5. We utilized the highly susceptible K18-hACE2 transgenic mouse model to assess disease progression, viral burden, and histopathology.ResultsDespite uniformly progressing to lethality in this model, the strains exhibited a distinct gradient in the kinetics and severity of disease. The Wild-type strain demonstrated the most rapid disease progression, highest viral loads across multiple organs (notably liver, brain, lung, and intestine), and most severe histopathological damage. The Delta variant showed an intermediate phenotype. Strikingly, the Omicron EG.5 variant displayed significantly attenuated pathogenicity, characterized by markedly delayed mortality, milder clinical presentation, and reduced tissue viral burden, yet it retained a capacity for multi-organ infection.DiscussionOur study provides direct experimental evidence for a pronounced attenuation in pathogenicity along the evolutionary trajectory from Wild-type through Delta to Omicron EG.5. These findings offer crucial insights for risk assessment of emerging variants and underscore the need for ongoing surveillance.

The intricate interactions between environmental exposures, the respiratory microbiome, and host genetic variations remain inadequately understood in the context of respiratory health. This study utilized sputum metagenomic data from 1,651 individuals in our previous cohort to elucidate these associations. Mendelian randomization indicated that air pollutants (e.g., SO2, CO, and PM2.5) were associated with lung function, which is potentially mediated by microbes, such as Actinomyces, Haemophilus influenzae, and Veillonella spp. Several genetic loci associated with respiratory microbiome variation were found to be linked to genotype-dependent associations between environmental exposures and lung function. For bacteria, the MEOX1 locus (rs1973191819) was associated with lower Filifactor alocis abundance under air pollutant exposure. The FAM110D (1:26157175) and USP36 (rs1343834070) loci showed associations with higher levels of certain pathogenic taxa (e.g., Ralstonia pickettii, Neisseria) and lower levels of the commensal Oribacterium, increasing chronic obstructive pulmonary disease (COPD) risk. For fungi, DNAJC18 and CCDC57 loci exhibited associations with Candida and Penicillium abundance, respectively. These genotype-dependent associations between the microbiome and environmental exposures provide insights into airway dysbiosis and susceptibility to respiratory diseases. IMPORTANCE:This study reveals why individuals exposed to identical air pollution exhibit varying degrees of respiratory severity, pointing to a critical missing link: our genetics. While pollution is a known disease trigger, our findings demonstrate that host genetic variation actively regulates and shapes the respiratory microbiome under environmental stress. By mapping specific genetic loci to pollutant-driven bacterial shifts, this work elucidates how host genetics filters environmental risks to govern microbial homeostasis. These results underscore the necessity of incorporating host-microbiome genetic regulation into environmental health research. Ultimately, this study shifts the paradigm toward personalized medicine, enabling the early identification of at-risk individuals and the development of targeted, microbiome-informed interventions.

GISDD, the Global Integrated Sequence and Genotyping Database for Dengue Virus (DENV), provides an integrated online analysis platform encompassing tools such as GISDDrlearn, GISDDprimer, and GISDDref, enabling swift identification and tracing of well-established DENV genotypes, subgenotypes, and clades, thereby facilitating a stratified global coordinated surveillance strategy.

Mucosal immunity is vital to provide effective protection against respiratory virus infections. However, the effective delivery of vaccine antigen to the respiratory mucosa is challenging because of the natural mucosal barrier. Here, we describe an approach exploiting the natural pulmonary surfactant (PS)-associated protein as a chaperone for transportation across the pulmonary mucosal barrier to enhance the lung resident memory T (TRM) cells, long-lived antibody response, and secretory immunoglobulin A (SIgA) generation via vaccination. Pulmonary immunization with an inhalable albumin-templated Mn nanoadjuvant (iMnNA)-formulated mucosal vaccine (MnVac) candidate promoted the in situ, local PS protein corona formation on iMnNA through binding to the albumin, thereby increasing the vaccine accumulation in pulmonary parenchyma and the antigen uptake by antigen-presenting cells (APCs). When formulated with a SARS-CoV-2 receptor-binding domain (RBD) dimer, this inhalable RBD-MnVac induced at least 3-fold higher and persistent (up to ∼240 days) RBD-specific antibody responses and higher frequencies in long-lived plasma cells (LLPC) in the bone marrow even at half antigen dose of the intramuscular immunization. The MnVac enhanced the systemic and local mucosal immune responses through activation of the stimulator of interferon genes (STING) pathway in the lung. Additionally, the heterosubtypic RBD dimer and influenza subunit MnVac extended the breadth of the protective antibody response against a number of viral variants. Overall, these findings support the use of iMnNA as a promising mucosal adjuvant candidate for fighting respiratory infectious diseases and future pandemics.

This study focuses on the cyclical epidemic characteristics of measles in Guangdong Province and constructs a non-autonomous SVEIR model that integrates seasonal transmission and vaccination dynamics, with a particular emphasis on analyzing the immune protection mechanisms of high-risk populations aged 0-24 months. This model introduces a time-varying propagation rate (Fourier function fitted to weekly data, R2 = 0.91), time-varying vaccination rate and vaccine protection rate, and optimizing vaccination strategies through optimal control theory. Mathematical analysis confirms that the basic reproduction number R0 represents the key threshold determining the persistence or extinction of measles, with estimated value as 0.87 (95% CI: 0.43-1.3). Numerical simulations indicate that sustaining a vaccination rate ( >= 99%) can suppress the annual incidence rate below 1/100,000. However, reducing the rate to 98.5% would trigger a sharp surge in cases within three years, with the incidence rate projected to reach 0.9 parts per thousand by 2030. Furthermore, vaccination efforts averted an estimated 80 million infections between 2005 and 2021. Optimization strategies indicate that prioritizing vaccination for the 0-2 age group can shorten the epidemic cycle by 30%, and real-time monitoring combined with vaccination coverage of >= 99% can achieve herd immunity.

Objectives Eliminating hepatitis B remains challenging, especially in Guangdong, the region with China's highest burden. Predicting incidence, optimizing vaccination, and reducing illness are essential to meet the WHO goal of a 90 % reduction by 2030. Methods Based on the HBV surveillance data from 2005 to 2022, disease clustering patterns, correlation between vaccination and incidence were determined. A six-compartment transmission model was established and validated by estimating infectivity using nonlinear least squares and polynomial fitting. Results From 2005 to 2022, acute HBV cases in Guangdong declined from 7509 to 2,097, while chronic cases in adults aged ≥15 rose from 38,595 to 146,658. High-risk clusters remained in Guangzhou, Foshan, and Shenzhen. Infant vaccination was linked to reduced acute infections but had limited effect on chronic cases. By 2030, acute HBV infectivity is projected to reach 1872 cases, with 100,354 new chronic infections expected in adults. To meet the WHO 2030 elimination target, average recovery time for chronic carriers must be reduced from 40 years to 7.7 years. For full elimination, it should be shortened to 1.85 years. Conclusions Infant vaccination curbed acute HBV in youth, but chronic cases in adults threaten elimination goals. Scaling therapies to accelerate chronic HBV recovery is urgent.

BackgroundCervical cancer, driven predominantly by persistent high-risk human papillomavirus (HPV) infection, ranks as the fourth most common malignancy in women worldwide. China faces barriers to achieving the World Health Organization (WHO) 2030 elimination targets due to low vaccination rates and complex demographics. Strategic intervention optimization is critical for accelerating elimination.MethodsWe developed an age-stratified deterministic compartmental model integrating demographic data and HPV transmission dynamics, capturing heterogeneity in age, sex, sexual activity, and intervention efficacy. The model simulated cervical cancer natural history, including HPV infection, progression to precancerous lesions, and invasive cancer and was calibrated using epidemiological data from the Global Burden of Disease. We evaluated multiple vaccination scenarios (varying coverage rates, age groups, and durations) to project incidence trajectories, estimate elimination timelines, and calculate the reproduction number. Sensitivity analyses were conducted to assess parameter effects.ResultsWithout vaccination, HPV infection becomes endemic (R0 = 1.38), causing 2.92 million cervical cancer cases in China during 2021 to 2070. Maintaining the 2020 vaccination rate would prevent 1.01 million cases in this period. While prioritizing females aged 15 to 26 y maximizes the per-dose impact, expanding vaccination to all females aged ≥15 y is essential for achieving elimination before 2040. Even single-year vaccination would confer >50-y protection. A higher vaccination rate accelerates elimination: annual rates of 0.09, 0.15, and 0.21 among females aged ≥15 y achieve elimination by 2037, 2035, and 2034, respectively, accelerating timelines by 15 to 20 y compared with strategies targeting only 15- to 26-y-olds.ConclusionsHPV vaccination is pivotal for reducing cervical cancer burden in China, with prioritizing women aged 15 to 26 y as the optimal strategy. Expanding vaccination to all women aged ≥15 y can accelerate the achievement of WHO elimination targets.HighlightsAn age-stratified model simulates HPV transmission patterns and assesses cervical cancer interventions.Without intervention, HPV remains endemic (R0 = 1.38), causing 2.92 million cervical cancer cases in China (2021-2070).Prioritizing 15- to 26-y-olds maximizes the per-dose impact, but expanding to 15+ y cohorts is essential for elimination.Even a single year of vaccination offers >50 y of protection.Females ≥15 y vaccinated annually at rates of 0.09, 0.15, and 0.21 achieve elimination by 2037, 2035, and 2034, respectively.

SARS-CoV-2 can encode circular RNAs (circRNAs); however, the potential effects of exogenous SARS-CoV-2 circRNAs on cardiovascular sequelae remain unknown. Three circRNAs derived from the nucleocapsid (N) gene of SARS-CoV-2, namely, circSARS-CV2-Ns, were identified for functional studies. In particular, circSARS-CV2-N1368 was shown to enhance platelet adhesiveness to endothelial cells (ECs) and inhibit EC-dependent vascular relaxation. Moreover, exogenous expression of circSARS-CV2-N1368 suppressed EC proliferation and migration and decreased angiogenesis and cardiac organoid beating. Mechanistically, we elucidated that circSARS-CV2-N1368 sponged the microRNA miR-103a-3p, which could reverse circSARS-CV2-N1368-induced EC damage. Additionally, activating transcription factor 7 (ATF7) was identified as a target gene of miR-103a-3p, and Toll-like receptor 4 (TLR4) was verified as a downstream gene of ATF7 that mediates circARS-CV2-N1368-induced activation of nuclear factor kappa B (NF-κB) signaling and ROS production in ECs. Importantly, the reactive oxygen species (ROS) scavenger NAC mitigated the circSARS-CV2-N1368-promoted EC impairment. Our findings reveal that the TLR4/NF-κB/ROS signal pathway is critical for mediating circSARS-CV2-N1368-promoted oxidative damage in ECs, providing insights into the endothelial impairment caused by circSARS-CV2-Ns.

BACKGROUND:Serological surveys of mumps are important for estimating susceptibility in the population and for evaluating the effectiveness of current vaccination strategies. METHODS:A cross-sectional serological survey using an enzyme-linked immunosorbent assay was conducted on 5,147 participants in Guangdong, China, to evaluate the immunological effects of 2 doses of measles-mumps-rubella vaccine. In accordance with the instructions of the ELISA kit, the final readings represent the anti-mumps antibody titers, which are expressed in "NovaTec units". RESULTS:Of the 5,147 participants, 3,888 were positive for mumps IgG antibodies, with a seroprevalence of 75.54% (95% CI: 74.34%-76.71%). For each age group, the mumps IgG seroprevalence rates were 74.40%, 89.02%, 85.58%, 68.60%, 69.28%, 78.42%, and 80.63% for those <8 months, 8 months-2 years, 3-5 years, 6-17 years, 18-39 years, 40-59 years, and>=60 years, respectively. In terms of the percentage decreases in anti-mumps antibody titers, in the population receiving the 1-dose vaccine, there was a mean decrease of 2.06% per year. In the population receiving 2 doses of the vaccine, the mean annual decreases were 10.33% and reached protective thresholds of approximately 12.3 years. CONCLUSION:The high mumps seroprevalence in the unvaccinated population revealed neglected hidden mumps infections. A time-lapse assay of IgG antibodies indicated that the mumps vaccine provided protection for one decade, which highlights that booster vaccinations may be needed in adults.

BackgroundDefining the immune dynamics of Japanese encephalitis (JE) in healthy individuals is crucial for assessing population susceptibility and evaluating the effectiveness of vaccinations.MethodsWe conducted a cross-sectional serological survey of anti-JEV IgG antibodies and anti-JEV neutralizing antibodies (nAbs) in Guangzhou City, Zhanjiang City and Heyuan City of Guangdong Province, China.ResultsA total of 691 participants were included from 2018-2022, among whom 50 were dengue IgG antibody positive and 641 were dengue IgG antibody negative. In the total population, the anti-JEV IgG antibody positivity rate detected by enzyme-linked immunosorbent assay (ELISA) was 51.37% (95% CI: 47.64-55.11%), and the neutralizing antibody positivity rate detected using the microneutralization test (MNT) was 73.22% (95% CI: 69.92-76.54%). Among the 641 dengue IgG antibody-negative subjects, the anti-JEV IgG antibody positivity rate by ELISA and the neutralizing antibody positivity rate by MNT were 48.05% (95% CI: 44.17-51.93%) and 72.07% (95% CI: 68.59-74.56%), respectively. Comparable geographical seroprevalences of either anti-JEV IgG or neutralizing antibody were observed in Guangzhou City, Heyuan City and Zhanjiang City, respectively (49.52% vs. 48.04% vs. 47.45%, 65.71% vs. 70.46% vs. 76.47%, respectively). Antibody positivity rates in all age groups exhibited a U-shaped curve, with the lowest rate occurring in the 7-18-year-old age group. With respect to the vaccine dose, the anti-JEV nAb positivity rate and geometric mean titer (GMT) detected by MNT were higher in those who received two doses of live attenuated vaccine than in those who received one dose or 0 doses (80.57% vs. 55.81% vs. 55.09% and 25.92 vs. 12.19 vs. 16.47, respectively). In the 641 dengue IgG antibody-negative subjects, moderate consistency between the MNT and ELISA results was observed (Kappa = 0.47, rs = 0.76).ConclusionThe high seroprevalence in participants indicated a neglected transmission of JE, which highlights the importance of strengthening the surveillance of JEV in this area. The vaccination program against JEV is highly needed because of immune gaps in adults, e.g., boosters for adults aged 7-39 years.

Exposure to environmental pollutants has been linked to increased antibiotic resistance, a critical global health challenge. The respiratory microbiome constitutes a key reservoir of antibiotic resistance genes (ARGs). Here, we constructed a respiratory ARG catalog from sputum metagenomes of 1,128 individuals. We demonstrate that exposures, particularly to cigarette smoke and biofuels, are associated with increased abundance and enhanced mobility of respiratory ARGs. These resistome alterations correlate inversely with lung function, with elevated mobile ARG abundance detectable even in individuals with mild airflow limitation within normal spirometry. Specific ARGs, including opmD and tet(K), interact with smoking in relation to lung function impairment. Murine experiments recapitulate these findings, showing exposure-induced increases in homologous ARGs that confer heightened phenotypic resistance in cultured respiratory bacteria. Our results elucidate a pathway through which environmental pollutants augment the respiratory resistome, suggesting the need for actions to mitigate the antimicrobial resistance burden by addressing environmental pollution.

Background: Although the National Measles Elimination Action Plan (NMEAP, 2006-2012) promoted a progress goal of measles elimination in China, the resurgence of measles in variety areas of China after NMEAP indicated a complexity between measles transmission and vaccination, and a regional in depth analysis was needed to assess it in population level which may guide for measles elimination in other west pacific countries.Methods: Measles surveillance and vaccination data during 2005-2021 in Guangdong, China was obtained from NNIDRIS and MSIIP system. We used interrupted event sequence (ITS model) and interrupted linear regression to quantitatively evaluate the intervention effect and persistence of immune strategy adjustment at different time nodes on the incidence. The effects of vaccination were assessed by using a kinetic model.Findings: Since the adjustment of measles vaccination strategy in Guangdong Province in September 2008, we observed the monthly and weekly reported incidence of measles decreased by 1.12/100000 and 0.05/100000 (P=0.004 and P=0.199) compared with that before vaccination, and the long-term effects decreased by 0.03/100000 and 0.002/100000 (P=0.141 and P=0.287) on average monthly and weekly. After MMR vaccination in June 2020, the monthly and weekly reported incidence of measles decreased by 0.002/100000 and 0.001/100000 (P=0.728 and P=0.334) compared with that before vaccination, but the long-term effects increased by 0.0006/100000 and 0.0002/100000 (P=0.456 and P=0.556) on average monthly and weekly. There was correlation between measles annual incidence rate with lagging 3 years, and vaccination rate was the strongest factor with it. In addition, the protection rate of two doses of vaccine (range 99.62%-99.98%) is greater than that of one dose (range 94.61%-99.95%). For children under two years of age, if the vaccination rate drops to 99% since Jan 2017 (2016), the small (large) epidemic would begin from 2018, and the number of cases reported will increase 1.68 times, 5.01 times, 15.60 times and 22.23 times (10.29 times, 32.12 times, 108.24 times and 166.35 times) respectively in each following year.Interpretation: We provide real-world evidence that the effect of combined immunization strategy of MV and MR may be better than that of single inoculation of MV. The short-term effect of MMR vaccination is better than other vaccines, but its long-term effect is still unclear. Two doses vaccine and high coverage is the key to reduce measles incidence. These findings will benefit policy-making of measles vaccination and prevention.Funding: This work was supported by grants The National Key Research and Development Program of China (2020YFC1200100), the Guangzhou Science and Technology Program (201904010012), the National Natural Science Foundation of China (12171116), and the Guangdong Science and Technology Program (2021B1212030007).Declaration of Interests: All the authors declare that they have no conflicts of interest.

The SARS-CoV-2 Omicron variant sparked the largest wave of infections worldwide. Mainland China eased its strict COVID-19 measures in late 2022 and experienced two nationwide Omicron waves in 2023. Here, we investigated lineage distribution and virus evolution in Guangdong, China, 2022-2023 by comparing 5813 local viral genomes with the datasets from other regions of China and worldwide. Additionally, we conducted three large-scale serological surveys involving 1696 participants to measure their immune response to the BA.5 and XBB.1.9 before and after the corresponding waves. Our findings revealed the Omicron variants, mainly the BA.5.2.48 lineage, causing infections in over 90% of individuals across different age groups within a month. This rapid spread led to the establishment of widespread immunity, limiting the virus’s ability to further adaptive mutation and dissemination. While similar immune responses to BA.5 were observed across all age groups after the initial wave, children aged 3 to 11 developed a stronger cross immune response to the XBB.1.9 strain, possibly explaining their lower infection rates in the following XBB.1 wave. Reinfection with Omicron XBB.1 variant triggered a more potent neutralizing immune response among older adults. These findings highlight the impact of age-specific immune responses on viral spread in potential future waves. Release of the zero-COVID policy in China in late 2022 led to two large Omicron-driven waves of infection in 2023. Here, the authors analyze virus genomes and serology data from before and after the two waves and describe changes in virus lineage distribution and age-specific antibody responses.

BACKGROUND:Viral hepatitis imposes a heavy disease burden worldwide and is also one of the most serious public health problems in China. We aimed to describe the epidemiological characteristics of hepatitis in China and to investigate the influencing factors. METHODS:We first used the JoinPoint model to analyze the percentage change (APC) and average annual percentage change (AAPC) of hepatitis in Chinese provinces from 2002 to 2021. We then explored the influencing factors by using the time-series global principal component analysis (GPCA) and the panel fixed-effects model. RESULTS:The disease burden varied across different provinces from 2002 to 2021. The AAPC of the total HAV incidence decreased by 10.39% (95% CI: [-12.70%, -8.02%]) from 2002 to 2021. Yet the AAPC of HBV, HCV, and HEV increased by 1.50% (95% CI: [0.23%, 2.79%]), 13.99% (95% CI: [11.28%, 16.77%]), and 7.10% (95% CI: [0.90%, 13.69%]), respectively. The hotspots of HAV, HBV, HCV, and HEV moved from the west to the center, from the northwest to the southeast, from the northeast to the whole country, and from the northeast to the southeast, respectively. Different types of viral hepatitis infections were associated with hygiene, pollutant, and meteorological factors. Their roles in spatial-temporal incidence were expressed by panel regression functions. CONCLUSIONS:Viral hepatitis infection in China showed spatiotemporal heterogeneity. Interventions should be tailored to its epidemiological characteristics and determinants of viral hepatitis.

Seroepidemiological characteristics of human papillomavirus (HPV) in community residents reflect natural infection and can guide the reform of vaccination programs. A population-based serological survey was conducted in Guangdong Province. Serum anti-HPV IgG antibody levels were determined by an ELISA. Neutralizing antibodies against HPV6, 11, 16, and 18 were detected via a pseudovirus-based neutralization assay (PBNA). A total of 5122 serum samples were collected from community residents, including 1989 males and 3133 females, in three cities of Guangdong Province. The rate of HPV IgG antibody positivity in females was 5.39% (95% CI: 4.6-6.2), which was greater than that in males (2.36%; 95% CI: 1.7-3.1). HPV IgG antibodies were more frequently detected in females aged 51-60 years (11.30%; 95% CI: 7.6-16.0), whereas in males, the detection increased with age and reached 4.94% (95% CI: 2.8-6.9) in the group aged ≥71 years. The seropositivity of neutralizing antibodies against HPV6 and 11 was greater than that against HPV16 and 18. The serum neutralizing antibody titers in individuals who received three doses of a vaccine were 7- to 12-fold greater than those in individuals who did not receive the vaccine. The neutralizing antibody titers slightly decreased within 40 months and ranged from 0.038 to 0.057 log ED50 per month. A moderate consistency between the HPV ELISA and PBNA results was observed (Kappa score = 0.49, r = 0.249, 0.635, 0.382, and 0.466 for HPV6, 11, 16, and 18, respectively). The HPV seropositivity rate among healthy residents of Guangdong Province was found to be low among children and adolescents and to increase with age. The serum neutralizing antibody titers were significantly greater in the vaccine group than that in the control group, and this difference persisted over time, which indicated promising protection against HPV infection.

ABSTRACT Dengue virus (DENV) gains genetic mutations during continuous transmission and evolution, making the virus more adaptive and virulent. The clade of DENV-1 genotype I has expanded and become the predominant genotype in Asia and the Pacific areas, but the underlying mechanisms are unclear. A combined analysis of nonsynonymous mutations in domain III of the envelope protein and their biological effects on virus pathogenesis and transmission was evaluated. Phylogenetic analyses found three nonsynonymous mutations (V324I, V351L, and V380I) in domain III of the envelope protein, which emerged in 1970s–1990s and stably inherited and expanded in contemporary strains after 2000. We generated reverse-mutated viruses (I324V, L351V, and I380V) based on an infectious clone of an epidemic DENV-1 strain (NIID02–20), and the results suggested that the infectivity of the contemporary epidemic virus (wild type, WT) has increased compared to the reverse mutant viruses in mammalian hosts but not mosquito vectors. The WT virus showed a higher binding affinity to host cells and increased virion stability. In addition, weaker immunogenicity and higher resistance to neutralizing antibodies of the WT virus indicated a trend of immune escape. The data suggested that nonsynonymous mutations of the E protein (V324I, V351L, and V380I) promote infectivity and immune evasion of DENV-1 genotype I, which may facilitate its onward transmission on a global scale. IMPORTANCE We provide evidence that minor sequence variation among dengue virus (DENV) strains can result in increased adaptability and virulence, impacting both the biology of the virus and the antiviral immune response. The genetic mutations of DENV-1 gained during continuous transmission and evolution will offer new clues for the design of novel vaccines against flaviviruses.

Intranasal vaccines, eliciting mucosal immune responses, can prevent early invasion, replication, and transmission of pathogens in the respiratory tract. However, the effective delivery of antigens through the nasal barrier and boosting of a robust systematic and mucosal immune remain challenges in intranasal vaccine development. Here, we describe an intranasally administered self-healing hydrogel vaccine with a reversible strain-dependent sol-gel transition by precisely modulating the self-assembly processes between the natural drug rhein and aluminum ions. The highly bioadhesive hydrogel vaccine enhances antigen stability and prolongs residence time in the nasal cavity and lungs by confining the antigen to the surface of the nasal mucosa, acting as a "mucosal mask". The hydrogel also stimulates superior immunoenhancing properties, including antigen internalization, cross-presentation, and dendritic cell maturation. Furthermore, the formulation recruits immunocytes to the nasal mucosa and nasal-associated lymphoid tissue (NALT) while enhancing antigen-specific humoral, cellular, and mucosal immune responses. Our findings present a promising strategy for preparing intranasal vaccines for infectious diseases or cancer.