Kynurenine-3-monooxygenase (KMO) broadly inhibits viral infections via triggering NMDAR/Ca2+ influx and CaMKII/ IRF3-mediated IFN-ß production.

Tryptophan (Trp) metabolism through the kynurenine pathway (KP) is well known to play a critical function in cancer, autoimmune and neurodegenerative diseases. However, its role in host-pathogen interactions has not been characterized yet. Herein, we identified that kynurenine-3-monooxygenase (KMO), a key rate-limiting enzyme in the KP, and quinolinic acid (QUIN), a key enzymatic product of KMO enzyme, exerted a novel antiviral function against a broad range of viruses. Mechanistically, QUIN induced the production of type I interferon (IFN-I) via activating the N-methyl-d-aspartate receptor (NMDAR) and Ca2+ influx to activate Calcium/calmodulin-dependent protein kinase II (CaMKII)/interferon regulatory factor 3 (IRF3). Importantly, QUIN treatment effectively inhibited viral infections and alleviated disease progression in mice. Furthermore, kmo-/- mice were vulnerable to pathogenic viral challenge with severe clinical symptoms. Collectively, our results demonstrated that KMO and its enzymatic product QUIN were potential therapeutics against emerging pathogenic viruses.

Exacerbated AIDS Progression by PD-1 Blockade during Therapeutic Vaccination in Chronically Simian Immunodeficiency Virus-Infected Rhesus Macaques after Interruption of Antiretroviral Therapy.

The persistence of cells latently infected with HIV-1, named the latent reservoir, is the major barrier to HIV-1 eradication, and the formation and maintenance of the latent reservoir might be exacerbated by activation of the immunoinhibitory pathway and dysfunction of CD8+ T cells during HIV-1 infection. Our previous findings demonstrated that prophylactic vaccination combined with PD-1 blockade generated distinct immune response profiles and conferred effective control of highly pathogenic SIVmac239 infection in rhesus macaques. However, to our surprise, herein we found that a therapeutic vaccination in combination with PD-1 blockade resulted in activation of the viral reservoir, faster viral rebound after treatment interruption, accelerated AIDS progression, and, ultimately, death in chronically SIV-infected macaques after antiretroviral therapy (ART) interruption. Our study further demonstrated that the SIV provirus was preferentially enriched in PD-1+CD4+ T cells due to their susceptibility to viral entry, potent proliferative ability, and inability to perform viral transcription. In addition, the viral latency was effectively reactivated upon PD-1 blockade. Together, these results suggest that PD-1 blockade may be a double-edged sword for HIV-1 immunotherapy and provide important insight toward the rational design of immunotherapy strategies for an HIV-1 cure. IMPORTANCE As it is one of the most challenging public health problems, there are no clinically effective cure strategies against HIV-1 infection. We demonstrated that prophylactic vaccination combined with PD-1 blockade generated distinct immune response profiles and conferred better control of highly pathogenic SIVmac239 infection in rhesus macaques. In the present study, to our surprise, PD-1 blockade during therapeutic vaccination accelerated the reactivation of latent reservoir and AIDS progression in chronically SIV-infected macaques after ART interruption. Our study further demonstrated that the latent SIV provirus was preferentially enriched in PD-1+CD4+ T cells because of its susceptibility to viral entry, inhibition of SIV transcription, and potent ability of proliferation, and the viral latency was effectively reactivated by PD-1 blockade. Therefore, PD-1 blockade might be a double-edged sword for AIDS therapy. These findings provoke interest in further exploring novel treatments against HIV-1 infection and other emerging infectious diseases.

The acceptance of SARS-CoV-2 rapid antigen self-testing: A cross-sectional study in China.

Compared with the nucleic acid amplification test (NATT), the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapid antigen self-testing (RAST) has advantages in speed and convenience. However, little is known about people's acceptance and influencing factors for SARS-CoV-2 RAST. A cross-sectional study was conducted from April 21 to 30, 2022 in China. The χ2 test and multivariate logistic regressions were used to identify the influencing factors. The structural equation model was used to test the extended protective motivation theory (PMT) model hypotheses. Among the total of 5107 participants, 62.5% were willing to accept the SARS-CoV-2 RAST. There were significant differences in acceptance among different residences (p < 0.001), educational level (p < 0.001), occupation (p < 0.001), monthly income (p < 0.001), travel frequency (p < 0.05), and feelings about NATT (p < 0.001). Response efficacy (ß = 0.05; p = 0.025) and self-efficacy (ß = 0.84; p < 0.001) had a positive effect, while response cost showed a negative effect (ß = -0.07; p < 0.001). The public's major concerns about SARS-CoV-2 RAST are its reliability, testing method, price, and authority. Overall, a moderate intention to use SARS-CoV-2 RAST was found among the Chinese population. The extended PMT can be used for the prediction of intention to accept the RAST. We need to take measures to increase people's acceptance of SARS-CoV-2 RAST.

Impact of combination preventative interventions on hospitalization and death under the pandemic of SARS-CoV-2 Omicron variant in China.

With a large population most susceptible to Omicron and emerging SARS-CoV-2 variants, China faces uncertain scenarios if reopening its border. Thus, we aimed to predict the impact of combination preventative interventions on hospitalization and death. An age-stratified susceptible-infectious-quarantined-hospitalized-removed-susceptible (SIQHRS) model based on the new guidelines of COVID-19 diagnosis and treatment (the ninth edition) was constructed to simulate the transmission dynamics of Omicron within 365 days. At baseline, we assumed no interventions other than 60% booster vaccination in individuals aged ≤60 years and 80% in individuals aged >60 years, quarantine and hospitalization. Oral antiviral medications for COVID-19 and nonpharmaceutical interventions (NPIs) such as social distancing and antigen self-testing were considered in subsequent scenarios. Sensitivity analyses were conducted to reflect different levels of interventions. A total of 0.73 billion cumulative quarantines (95% CI 0.53-0.83), 33.59 million hospitalizations (22.41-39.31), and 0.62 million deaths (0.40-0.75) are expected in 365 days. The case fatality rate with pneumonia symptoms (moderate, severe and critical illness) is expected to be 1.83% (1.68-1.99%) and the infected fatality rate is 0.38‰ (0.33-0.4‰). The highest existing hospitalization and ICU occupations are 3.11 (0.30-3.85) and 20.33 (2.01-25.20) times of capacity, respectively. Sensitivity analysis showed that interventions can be adjusted to meet certain conditions to reduce the total number of infections and deaths. In conclusion, after sufficient respiratory and ICU beds are prepared and the relaxed NPIs are in place, the SARS-CoV-2 Omicron variant would not seriously impact the health system.

Characteristics of genotype, drug resistance, and molecular transmission network among newly diagnosed HIV-1 infections in Shenzhen, China.

The HIV-1 pandemic has persisted for four decades, and poses a major challenge to global public health. Shenzhen, a city with large number of migrant populations in China, is suffering HIV-1 epidemic. It is necessary to continuously conduct the molecular surveillance among newly diagnosed HIV-1 patients in these migrant population. In this study, plasma samples of newly diagnosed and ART-naive HIV-1 infections were collected from Shenzhen city in China. The partial genes of HIV-1 gag and pol were amplified and sequenced for the analysis of genotype, drug resistance, and molecular transmission network. Ninety-one sequences of pol gene were obtained from newly diagnosed HIV-1 infections in Shenzhen, and seven HIV-1 subtypes were revealed in this investigation. Among them, the circulating recombinant form (CRF) 07_BC was the mostly frequent subtype (53.8%, 49/91), followed by CRF01_AE (20.9%, 19/91), CRF55_01B (9.9%, 9/91), unique recombinant forms (URFs) (8.8%, 8/91), B (3.3%, 3/91), CRF59_01B (2.2%, 2/91), and CRF08_BC (1.1%, 1/91). The overall prevalence of pretreatment drug resistance (PDR) was 23.1% (21/91), and 52.38% (11/21) of the PDR was specific for the nonnucleotide reverse transcriptase inhibitors (NNRTIs). Furthermore, a total of 3091 pol gene sequences were used to generate 19 molecular transmission clusters, and then one growing cluster, a new cluster, and a cluster with growth reactivation were identified. The result revealed that more sexual partner, CRF_07BC subtype, and seven amino acid deletions in gag p6 region might be the influencing factors associated with the high risk of transmission behavior. Compared with CRF01_AE subtype, CRF07_BC subtype strains were more likely to form clusters in molecular transmission network. This suggests that long-term surveillance of the HIV-1 molecular transmission should be a critical measure to achieve a precise intervention for controlling the spread of HIV-1 in China.

College students' influence on COVID-19 vaccination uptake among seniors in China: a protocol of combined cross-sectional and experimental study.

BACKGROUND: College students generally have good knowledge about COVID-19 and may facilitate COVID-19 vaccination in family. The purpose of this study is to understand college students' willingness to persuade their grandparents to initiate COVID-19 vaccination and the effect of their persuasion. METHODS: A combined cross-sectional and experimental study will be conducted online. In the cross-sectional study (Phase I), eligible participants are college students who are aged ≥ 16 years and have at least one living grandparent aged ≥ 60 years who has/have not completed the COVID-19 vaccination. Participants self-complete Questionnaire A to collect information on the socio-demographics of themselves and their grandparents, their knowledge about older adults' COVID-19 vaccination, as well as Health Belief Model (HBM) and Theory of Planned Behavior (TPB) predictor variables. The primary outcome at Phase I is college students' willingness to persuade grandparents to receive COVID-19 vaccines. Those who are willing to persuade grandparents and participate in a follow-up survey will be invited to participate in a randomized controlled trial (Phase II). At Phase II, eligible participants are those who have at least one living grandparent aged ≥ 60 years who completed the COVID-19 initial vaccination series but has/have not received a booster dose. At the baseline, participants self-complete Questionnaire B to collect information on individual grandparents' COVID-19 vaccination status, attitude towards and intention to COVID-19 booster dose. Participants will then be randomly allocated 1:1 to either intervention arm (one-week smartphone-based health education on older adults' COVID-19 vaccination plus two weeks' waiting period) or control arm (three weeks' waiting period). At the end of week three, participants in both arms self-complete Questionnaire C to collect information on their grandparents' COVID-19 vaccination status. The primary outcome at Phase II is the uptake rate of COVID-19 booster dose among grandparents. Secondary outcomes include grandparents' attitude and intention to get a COVID-19 booster dose. DISCUSSION: No previous study had measured the effect of college students' persuasion on COVID-19 vaccination uptake in older adults. Findings from this study will provide evidence for innovative and potentially feasible interventions that further promote COVID-19 vaccination in older adults. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2200063240. Registered 2 September 2022.

IFN-Inducible SerpinA5 Triggers Antiviral Immunity by Regulating STAT1 Phosphorylation and Nuclear Translocation.

Deeply understanding virus-host interactions is a prerequisite for developing effective strategies to control frequently emerging infectious diseases, which have become a serious challenge for global public health. The type I interferon (IFN)-mediated JAK/STAT pathway is well known for playing an essential role in host antiviral immunity, but the exact regulatory mechanisms of various IFN-stimulated genes (ISGs) are not yet fully understood. We herein reported that SerpinA5, as a novel ISG, played a previously unrecognized role in antiviral activity. Mechanistically, SerpinA5 can upregulate the phosphorylation of STAT1 and promote its nuclear translocation, thus effectively activating the transcription of IFN-related signaling pathways to impair viral infections. Our data provide insights into SerpinA5-mediated innate immune signaling during virus-host interactions.

Mucosal Priming with a Recombinant Influenza A Virus-Vectored Vaccine Elicits T-Cell and Antibody Responses to HIV-1 in Mice.

Recombinant influenza A viral (IAV) vectors are potential to stimulate systemic and mucosal immunity, but the packaging capacity is limited and only one or a few epitopes can be carried. Here, we report the generation of a replication-competent IAV vector that carries a full-length HIV-1 p24 gene linked to the 5'-terminal coding region of the neuraminidase segment via a protease cleavage sequence (IAV-p24). IAV-p24 was successfully rescued and stably propagated, and P24 protein was efficiently expressed in infected mammalian cells. In BALB/c mice, IAV-p24 showed attenuated pathogenicity compared to that of the parental A/PR/8/34 (H1N1) virus. An intranasal inoculation with IAV-p24 elicited moderate HIV-specific cell-mediated immune (CMI) responses in the airway and vaginal tracts and in the spleen, and an intranasal boost with a replication-incompetent adenovirus type 2 vector expressing the HIV-1 gag gene (Ad2-gag) greatly improved these responses. Importantly, compared to an Ad2-gag prime plus IAV-p24 boost regimen, the IAV-p24 prime plus Ad2-gag boost regimen had a greater efficacy in eliciting HIV-specific CMI responses. P24-specific CD8+ T cells and antibodies were robustly provoked both systemically and in mucosal sites and showed long-term durability, revealing that IAV-p24 may be used as a mucosa-targeted priming vaccine. Our results illustrate that IAV-p24 is able to prime systemic and mucosal immunity against HIV-1 and warrants further evaluation in nonhuman primates.IMPORTANCE An effective HIV-1 vaccine remains elusive despite nearly 40 years of research. CD8+ T cells and protective antibodies may both be desirable for preventing HIV-1 infection in susceptible mucosal sites. Recombinant influenza A virus (IAV) vector has the potential to stimulate these immune responses, but the packaging capacity is extremely limited. Here, we describe a replication-competent IAV vector expressing the HIV-1 p24 gene (IAV-p24). Unlike most other IAV vectors that carried one or several antigenic epitopes, IAV-p24 stably expressed the full-length P24 protein, which contains multiple epitopes and is highly conserved among all known HIV-1 sequences. Compared to the parental A/PR/8/34 (H1N1) virus, IAV-p24 showed an attenuated pathogenicity in BALB/c mice. When combined with an adenovirus vector expressing the HIV-1 gag gene, IAV-p24 was able to prime P24-specific systemic and mucosal immune responses. IAV-p24 as an alternative priming vaccine against HIV-1 warrants further evaluation in nonhuman primates.

Vaccination strategy for preventing the spread of SARS-CoV-2 in the limited supply condition: A mathematical modeling study.

To mitigate SARS-CoV-2 transmission, vaccines have been urgently approved. With their limited availability, it is critical to distribute the vaccines reasonably. We simulated the SARS-CoV-2 transmission for 365 days over four intervention periods: free transmission, structural mitigation, personal mitigation, and vaccination. Sensitivity analyses were performed to obtain robust results. We further evaluated two proposed vaccination allocations, including one-dose-high-coverage and two-doses-low-coverage, when the supply was low. 33.35% (infection rate, 2.68 in 10 million people) and 40.54% (2.36) of confirmed cases could be avoided as the nonpharmaceutical interventions (NPIs) adherence rate rose from 50% to 70%. As the vaccination coverage reached 60% and 80%, the total infections could be reduced by 32.72% and 41.19%, compared to the number without vaccination. When the durations of immunity were 90 and 120 days, the infection rates were 2.67 and 2.38. As the asymptomatic infection rate rose from 30% to 50%, the infection rate increased 0.92 (SD, 0.16) times. Conditioned on 70% adherence rate, with the same amount of limited available vaccines, the 20% and 40% vaccination coverage of one-dose-high-coverage, the infection rates were 2.70 and 2.35; corresponding to the two-doses-low-coverage with 10% and 20% vaccination coverage, the infection rates were 3.22 and 2.92. Our results indicated as the duration of immunity prolonged, the second wave of SARS-CoV-2 would be delayed and the scale would be declined. On average, the total infections in two-doses-low-coverage was 1.48 times (SD, 0.24) as high as that in one-dose-high-coverage. It is crucial to encourage people in order to improve vaccination coverage and establish immune barriers. Particularly when the supply is limited, a wiser strategy to prevent SARS-CoV-2 is equally distributing doses to the same number of individuals. Besides vaccination, NPIs are equally critical to the prevention of widespread of SARS-CoV-2.

Acceptance of COVID-19 booster vaccination based on the protection motivation theory: A cross-sectional study in China.

The promotion of the booster shots against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is an open issue to be discussed. Little is known about the public intention and the influencing factors regarding the booster vaccine. A cross-sectional survey in Chinese adults was conducted using an online questionnaire, which designed on the basis of protection motivation theory (PMT) scale and vaccine hesitancy scale (VHS). Hierarchical multiple regression was used to compare the fitness of the PMT scale and VHS for predicting booster vaccination intention. Multivariable logistic regression was used to analyze the factors associated with the acceptance. Six thousand three hundred twenty-one (76.8%) of participants were willing to take the booster shot. However, the rest of the participants (23.2%) were still hesitant to take the booster vaccine. The PMT scale was more powerful than the VHS in explaining the vaccination intention. Participants with high perceived severity (adjusted odds ratio [aOR] = 0.69) and response cost (aOR = 0.47) were less willing to take the booster shots, but participants with high perceived susceptibility (aOR = 1.19), response efficacy (aOR = 2.13), and self-efficacy (aOR = 3.33) were more willing to take the booster shots. In summary, interventions based on PMT can provide guidance to ensure the acceptance of the booster vaccine.

Broadly Antiviral Activities of TAP1 through Activating the TBK1-IRF3-Mediated Type I Interferon Production.

Deeply understanding the virus-host interaction is a prerequisite for developing effective anti-viral strategies. Traditionally, the transporter associated with antigen processing type 1 (TAP1) is critical for antigen presentation to regulate adaptive immunity. However, its role in controlling viral infections through modulating innate immune signaling is not yet fully understood. In the present study, we reported that TAP1, as a product of interferon-stimulated genes (ISGs), had broadly antiviral activity against various viruses such as herpes simplex virus 1 (HSV-1), adenoviruses (AdV), vesicular stomatitis virus (VSV), dengue virus (DENV), Zika virus (ZIKV), and influenza virus (PR8) etc. This antiviral activity by TAP1 was further confirmed by series of loss-of-function and gain-of-function experiments. Our further investigation revealed that TAP1 significantly promoted the interferon (IFN)-ß production through activating the TANK binding kinase-1 (TBK1) and the interferon regulatory factor 3 (IRF3) signaling transduction. Our work highlighted the broadly anti-viral function of TAP1 by modulating innate immunity, which is independent of its well-known function of antigen presentation. This study will provide insights into developing novel vaccination and immunotherapy strategies against emerging infectious diseases.

Efficacy of HIV interventions among factory workers in low- and middle-income countries: a systematic review.

BACKGROUND: Factory workers in low- and middle-income countries (LMICs) are vulnerable to HIV transmission. Interventions are needed to prevent HIV in this population. We systematically reviewed published literature on the efficacy of various HIV interventions in reducing stigma, risk behaviors and HIV transmission among factory workers. METHODS: A systematic review was performed using predefined inclusion and exclusion criteria. Four databases (PubMed, PsycINFO, Scopus and EMBASE) were searched for relevant publications between January 1, 1990 and December 31, 2018. Two independent reviewers assessed the methodological quality of studies. RESULTS: Thirteen articles were included, with 2 randomized controlled trials and 11 cohort studies. Five interventions and their combinations were summarized. Educational intervention increased condom use and reduced the use of recreational drugs and alcohol before sex. Community intervention that proactively provide HIV counselling and testing (HCT) services could increase the detection rate of HIV and other sexually transmitted diseases (STDs). Lottery intervention increased HCT uptake and decreased HIV public stigma. Education combined with community intervention reduced the proportion of workers with casual sex and enhanced HIV knowledge. Peer education combined with community intervention increased the proportion of workers who were willing to take their partners to HCT. Policy intervention combined with peer education enhanced HIV knowledge, perceived condom accessibility and condom use with regular partners. CONCLUSIONS: Various interventions improved HIV knowledge, decreased HIV stigma and reduced HIV-related risk behaviors among factory workers in LMICs. The combination of multiple interventions tended to achieve better efficacy than a single intervention. Persistent combination interventions are essential to address HIV in this population.

Proton Channel Activity of Influenza A Virus Matrix Protein 2 Contributes to Autophagy Arrest.

Influenza A virus infection can arrest autophagy, as evidenced by autophagosome accumulation in infected cells. Here, we report that this autophagosome accumulation can be inhibited by amantadine, an antiviral proton channel inhibitor, in amantadine-sensitive virus infected cells or cells expressing influenza A virus matrix protein 2 (M2). Thus, M2 proton channel activity plays a role in blocking the fusion of autophagosomes with lysosomes, which might be a key mechanism for arresting autophagy.

Mucosal priming with a replicating-vaccinia virus-based vaccine elicits protective immunity to simian immunodeficiency virus challenge in rhesus monkeys.

Mucosal surfaces are not targeted by most human immunodeficiency virus type 1 (HIV-1) vaccines, despite being major routes for HIV-1 transmission. Here we report a novel vaccination regimen consisting of a mucosal prime with a modified replicating vaccinia virus Tiantan strain (MVTT(SIVgpe)) and an intramuscular boost with a nonreplicating adenovirus strain (Ad5(SIVgpe)). This regimen elicited robust cellular immune responses with enhanced magnitudes, sustainability, and polyfunctionality, as well as higher titers of neutralizing antibodies against the simian immunodeficiency virus SIV(mac1A11) in rhesus monkeys. The reductions in peak and set-point viral loads were significant in most animals, with one other animal being protected fully from high-dose intrarectal inoculation of SIV(mac239). Furthermore, the animals vaccinated with this regimen were healthy, while ~75% of control animals developed simian AIDS. The protective effects correlated with the vaccine-elicited SIV-specific CD8(+) T cell responses against Gag and Pol. Our study provides a novel strategy for developing an HIV-1 vaccine by using the combination of a replicating vector and mucosal priming.

The 2nd China Vaccinology Integrated Innovation & Teaching Development Conference: Promoting the construction of vaccinology discipline system.

The 2nd China Vaccinology Integrated Innovation & Teaching Development Conference was held in Sun Yat-sen University, Shenzhen, 18-19, November 2023. Over 200 participants in the field of Vaccinology gathered together to address challenges and issues relevant to vaccine education and training courses, research, and public health programs in China. The conference themed "Promoting the Integrated and Innovative Development of Vaccinology through Collective Efforts." The conference was organized by the China Association of Vaccine (CAV) and hosted by Vaccinology Education Professional Committee of CAV, and School of Public Health (Shenzhen), Sun Yat-sen University. Other partners included the Medical Virology Branch of the Chinese Medical Association, the editorial committee of the Chinese Journal of Preventive Medicine, Human Vaccines & Immunotherapeutics, and the People's Medical Publishing House. The 1st conference was held in Hangzhou, in October 2020.

In silico design of a broad-spectrum multiepitope vaccine against influenza virus.

Influenza remains a global health concern due to its potential to cause pandemics as a result of rapidly mutating influenza virus strains. Existing vaccines often struggle to keep up with these rapidly mutating flu viruses. Therefore, the development of a broad-spectrum peptide vaccine that can stimulate an optimal antibody response has emerged as an innovative approach to addressing the influenza threat. In this study, an immunoinformatic approach was employed to rapidly predict immunodominant epitopes from different antigens, aiming to develop an effective multiepitope influenza vaccine (MEV). The immunodominant B-cell linear epitopes of seasonal influenza strains hemagglutinin (HA) and neuraminidase (NA) were predicted using an antibody-peptide microarray, involving a human cohort including vaccinees and infected patients. On the other hand, bioinformatics tools were used to predict immunodominant cytotoxic T-cell (CTL) and helper T-cell (HTL) epitopes. Subsequently, these epitopes were evaluated by various immunoinformatic tools. Epitopes with high antigenicity, high immunogenicity, non-allergenicity, non-toxicity, as well as exemplary conservation were then connected in series with appropriate linkers and adjuvants to construct a broad-spectrum MEV. Moreover, the structural analysis revealed that the MEV candidates exhibited good stability, and the docking results demonstrated their strong affinity to Toll-like receptors 4 (TLR4). In addition, molecular dynamics simulation confirmed the stable interaction between TLR4 and MEVs. Three injections with MEVs showed a high level of B-cell and T-cell immune responses according to the immunological simulations in silico. Furthermore, in-silico cloning was performed, and the results indicated that the MEVs could be produced in considerable quantities in Escherichia coli (E. coli). Based on these findings, it is reasonable to create a broad-spectrum MEV against different subtypes of influenza A and B viruses in silico.

Association between Statins Administration and Influenza Susceptibility: A Systematic Review and Meta-Analysis of Longitudinal Studies.

Previous studies reported that the association between statins use and influenza infection was contradictory. A systematic review and meta-analysis of longitudinal studies were performed to determine the association between statins use and influenza susceptibility. The literature search was conducted in PubMed, Embase, and Web of Science, from each database's inception to 21 May 2023. The fixed effect model and random effects model were used for data synthesis. In our study, a total of 1,472,239 statins users and 1,486,881 statins non-users from five articles were included. The pooled risk ratio (RR) of all included participants was 1.05 (95% CI: 1.03-1.07), and there were still significant differences after adjusting for vaccination status. Of note, RR values in statins users were 1.06 (95% CI: 1.03-1.08) in people aged ≥60 years old and 1.05 (95% CI: 1.03-1.07) in participant groups with a higher proportion of females. Administration of statins might be associated with an increased risk of influenza infection, especially among females and elderly people. For those people using statins, we should pay more attention to surveillance of their health conditions and take measures to prevent influenza infection.

Influence of grandchildren on COVID-19 vaccination uptake among older adults in China: a parallel-group, cluster-randomized controlled trial.

The uptake of COVID-19 booster vaccination among older adults in China is suboptimal. Here, we report the results of a parallel-group cluster-randomized controlled trial evaluating the efficacy of promoting COVID-19 booster vaccination among grandparents (≥60 years) through a health education intervention delivered to their grandchildren (aged ≥16 years) in a Chinese cohort (Chinese Clinical Trial Registry: ChiCTR2200063240 ). The primary outcome was the uptake rate of COVID-19 booster dose among grandparents. Secondary outcomes include grandparents' attitude and intention to get a COVID-19 booster dose. A total of 202 college students were randomized 1:1 to either the intervention arm of web-based health education and 14 daily reminders (n = 188 grandparents) or control arm (n = 187 grandparents) and reported their grandparents' COVID-19 booster vaccination status at baseline and 21 days. Grandparents in the intervention arm were more likely to receive COVID-19 booster vaccination compared to control cohort (intervention, 30.6%; control, 16.9%; risk ratio = 2.00 (95% CI, 1.09 to 3.66)). Grandparents in the intervention arm also had greater attitude change (ß = 0.28 (95% CI, 0.04 to 0.52)) and intention change (ß = 0.32 (95% CI, 0.12 to 0.52)) to receive a COVID-19 booster dose. Our results show that an educational intervention targeting college students increased COVID-19 booster vaccination uptake among grandparents in China.

Network-based approach for drug repurposing against mpox.

The current outbreak of mpox presents a significant threat to the global community. However, the lack of mpox-specific drugs necessitates the identification of additional candidates for clinical trials. In this study, a network medicine framework was used to investigate poxviruses-human interactions to identify potential drugs effective against the mpox virus (MPXV). The results indicated that poxviruses preferentially target hubs on the human interactome, and that these virally-targeted proteins (VTPs) tend to aggregate together within specific modules. Comorbidity analysis revealed that mpox is closely related to immune system diseases. Based on predicted drug-target interactions, 268 drugs were identified using the network proximity approach, among which 23 drugs displaying the least side-effects and significant proximity to MPXV were selected as the final candidates. Lastly, specific drugs were explored based on VTPs, differentially expressed proteins, and intermediate nodes, corresponding to different categories. These findings provide novel insights that can contribute to a deeper understanding of the pathogenesis of MPXV and development of ready-to-use treatment strategies based on drug repurposing.

Circumventing antivector immunity by using adenovirus-infected blood cells for repeated application of adenovirus-vectored vaccines: proof of concept in rhesus macaques.

Adenovirus has been extensively exploited as a vector platform for delivering vaccines. However, preexisting antiadenovirus immunity is the major stumbling block for application of adenovirus-vectored vaccines. In this study, we found that freshly isolated peripheral blood mononuclear cells (PBMCs), mostly CD14(+) cells, from adenovirus serotype 5 (Ad5)-seropositive primates (humans and rhesus macaques) can be efficiently infected with Ad5 in vitro. On the basis of this observation, a novel strategy based on adenoviral vector-infected PBMC (AVIP) immunization was explored to circumvent antivector immunity. Autologous infusion of Ad5-SIVgag-infected PBMCs elicited a strong Gag-specific cellular immune response but induced weaker Ad5-neutralizing antibody (NAb) in Ad5-seronegative macaques than in macaques intramuscularly injected with Ad5-SIVgag. Moreover, Ad5-seropositive macaques receiving multiple AVIP immunizations with Ad5-SIVenv, Ad5-SIVgag, and Ad5-SIVpol vaccines elicited escalated Env-, Gag-, and Pol-specific immune responses after each immunization that were significantly greater than those in macaques intramuscularly injected with these Ad5-SIV vaccines. After challenged intravenously with a highly pathogenic SIVmac239 virus, macaques receiving AVIP immunization demonstrated a significant reduction in viral load at both the peak time and set-point period compared with macaques without Ad5-SIV vaccines. Our study warranted further research and development of the AVIP immunization as a platform for repeated applications of adenovirus-vectored vaccines.