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1.
J Infect Chemother ; 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-38977072

ABSTRACT

Respiratory viral infections, including respiratory syncytial virus (RSV), parainfluenza viruses and type A and B influenza viruses, can have severe outcomes. Bacterial infections frequently follow viral infections, and influenza or other viral epidemics periodically have higher mortalities from secondary bacterial pneumonias. Most secondary bacterial infections can cause lung immunosuppression by fatty acid mediators which activate cellular receptors to manipulate neutrophils, macrophages, natural killer cells, dendritic cells and other lung immune cells. Bacterial infections induce synthesis of inflammatory mediators including prostaglandins and leukotrienes, then eventually also special pro-resolving mediators, including lipoxins, resolvins, protectins and maresins, which normally resolve inflammation and immunosuppression. Concurrent viral and secondary bacterial infections are more dangerous, because viral infections can cause inflammation and immunosuppression before the secondary bacterial infections worsen inflammation and immunosuppression. Plausibly, the higher mortalities of secondary bacterial pneumonias are caused by the overwhelming inflammation and immunosuppression, which the special pro-resolving mediators might not resolve.

2.
Influenza Other Respir Viruses ; 18(7): e13352, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39005150

ABSTRACT

BACKGROUND: Global influenza-associated acute respiratory infections contribute to 3-5 million severe illnesses requiring hospitalization annually, with 90% of hospitalizations occurring among children < 5 years in developing countries. In Bangladesh, the inadequate availability of nationally representative, robust estimates of influenza-associated hospitalizations limits allocation of resources for prevention and control measures. METHODS: This study used data from the hospital-based influenza surveillance (HBIS) system in Bangladesh from 2010 to 2019 and healthcare utilization surveys to determine hospital utilization patterns in the catchment area. We estimated annual influenza-associated hospitalization numbers and rates for all age groups in Bangladesh using WHO methods, adjusted for a 6-day-a-week enrollment schedule, selective testing of specimens from children under five, and healthcare-seeking behavior, based on the proportion of symptomatic community participants seeking healthcare within the past week. We then estimated national hospitalization rates by multiplying age-specific hospitalization rates with the corresponding annual national census population. RESULTS: Annual influenza-associated hospitalization rates per 100,000 population for all ages ranged from 31 (95% CI: 27-36) in 2011 to 139 (95% CI: 130-149) in 2019. Children < 5 years old had the highest rates of influenza-associated hospitalization, ranging from 114 (95% CI: 90-138) in 2011 to 529 (95% CI: 481-578) in 2019, followed by adults aged ≥ 65 years with rates ranging from 46 (95% CI: 34-57) in 2012 to 252 (95% CI: 213-292) in 2019. The national hospitalization estimates for all ages during 2010-2019 ranged from 47,891 to 236,380 per year. CONCLUSIONS: The impact of influenza-associated hospitalizations in Bangladesh may be considerable, particularly for young children and older adults. Targeted interventions, such as influenza vaccination for these age groups, should be prioritized and evaluated.


Subject(s)
Hospitalization , Influenza, Human , Humans , Bangladesh/epidemiology , Hospitalization/statistics & numerical data , Influenza, Human/epidemiology , Child, Preschool , Child , Infant , Adult , Incidence , Adolescent , Middle Aged , Young Adult , Aged , Female , Male , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/virology , Infant, Newborn , Aged, 80 and over , Acute Disease/epidemiology
3.
J Infect Dis ; 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39012796

ABSTRACT

Intranasal M2SR (M2-deficient Single Replication influenza virus) vaccine induces robust immune responses in animal models and human subjects. A high-throughput multiplexed platform was used to analyze hemagglutinin-specific mucosal antibody responses in adults after a single dose of H3N2 M2SR. Nasal swab specimens were analyzed for total and hemagglutinin-specific IgA. Significant, dose-dependent increases in mucosal antibody responses to vaccine-matched and drifted H3N2 hemagglutinin were observed in M2SR vaccinated subjects regardless of baseline serum and mucosal immune status. These data suggest that M2SR induces broadly cross-reactive mucosal immune responses which may provide better protection against drifted and newly emerging influenza strains.

4.
ACS Nano ; 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39013014

ABSTRACT

Viral ribonucleoproteins (vRNPs) are the cornerstones of viral proliferation, as they form the macromolecular complexes that are responsible for the transcription and replication of most single-stranded RNA viruses. The influenza A virus (IAV) polymerase catalyzes RNA synthesis within the context of vRNPs where genomic viral RNA (vRNA) is packaged by the viral nucleoprotein (NP). We used high-speed atomic force microscopy and electron microscopy to study the conformational dynamics of individual IAV recombinant RNPs (rRNPs) during RNA synthesis. The rRNPs present an annular organization that allows for the real-time tracking of conformational changes in the NP-vRNA template caused by the advancing polymerase. We demonstrate that the rRNPs undergo a well-defined conformational cycle during RNA synthesis, which can be interpreted in light of previous transcription models. We also present initial estimations of the average RNA synthesis rate in the rRNP and its dependence on the nucleotide concentration and stability of the nascent RNA secondary structures. Furthermore, we provide evidence that rRNPs can perform consecutive cycles of RNA synthesis, accounting for their ability to recycle and generate multiple copies of RNA.

5.
Virulence ; 15(1): 2379371, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39014540

ABSTRACT

The economic losses caused by high pathogenicity (HP) avian influenza viruses (AIV) in the poultry industry worldwide are enormous. Although chickens and turkeys are closely related Galliformes, turkeys are thought to be a bridging host for the adaptation of AIV from wild birds to poultry because of their high susceptibility to AIV infections. HPAIV evolve from low pathogenicity (LP) AIV after circulation in poultry through mutations in different viral proteins, including the non-structural protein (NS1), a major interferon (IFN) antagonist of AIV. At present, it is largely unknown whether the virulence determinants of HPAIV are the same in turkeys and chickens. Previously, we showed that mutations in the NS1 of HPAIV H7N1 significantly reduced viral replication in chickens in vitro and in vivo. Here, we investigated the effect of NS1 on the replication and virulence of HPAIV H7N1 in turkeys after inoculation with recombinant H7N1 carrying a naturally truncated wild-type NS1 (with 224 amino-acid "aa" in length) or an extended NS1 with 230-aa similar to the LP H7N1 ancestor. There were no significant differences in multiple-cycle viral replication or in the efficiency of NS1 in blocking IFN induction in the cell culture. Similarly, all viruses were highly virulent in turkeys and replicated at similar levels in various organs and swabs collected from the inoculated turkeys. These results suggest that NS1 does not play a role in the virulence or replication of HPAIV H7N1 in turkeys and further indicate that the genetic determinants of HPAIV differ in these two closely related galliform species.


Subject(s)
Chickens , Influenza A Virus, H7N1 Subtype , Influenza in Birds , Turkeys , Viral Nonstructural Proteins , Viral Tropism , Virus Replication , Animals , Turkeys/virology , Viral Nonstructural Proteins/genetics , Viral Nonstructural Proteins/metabolism , Influenza in Birds/virology , Influenza A Virus, H7N1 Subtype/genetics , Influenza A Virus, H7N1 Subtype/pathogenicity , Chickens/virology , Virulence , Poultry Diseases/virology
6.
Can J Public Health ; 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39017909

ABSTRACT

SETTING: Task sharing can fill health workforce gaps, improve access to care, and enhance health equity by redistributing health services to providers with less training. We report learnings from a demonstration project designed to assess whether lay student vaccinators can support community immunizations. INTERVENTION: Between July 2022 and February 2023, 27 undergraduate and graduate students were recruited from the University of Toronto Emergency First Responders organization and operated 11 immunization clinics under professional supervision. Medical directives, supported with online and in-person training, enabled lay providers to administer and document vaccinations when supervised by nurses, physicians, or pharmacists. Participants were invited to complete a voluntary online survey to comment on their experience. OUTCOMES: Lay providers administered 293 influenza and COVID-19 vaccines without adverse events. A total of 141 participants (122 patients, 17 lay vaccinators, 1 nurse, and 1 physician) responded to our survey. More than 80% of patients strongly agreed to feeling safe and comfortable with lay providers administering vaccines under supervision, had no concerns with lay vaccinators, and would attend another lay vaccinator clinic. Content and thematic analysis of open-text responses revealed predominantly positive experiences, with themes about excellent vaccinators, organized and efficient clinics, and the importance of training, communication, and access to regulated professionals. The responding providers expressed comfort working in collaborative immunization teams. IMPLICATIONS: Lay student providers can deliver vaccines safely under a medical directive while potentially improving patient experiences. Rather than redeploying scarce professionals, task sharing strategies could position trained lay vaccinators to support immunizations, improve access, and foster community engagement.


RéSUMé: LIEU: Le partage de tâches peut combler les pénuries de personnels de santé et améliorer l'accès aux soins et l'équité en santé en redistribuant les services de santé vers des prestataires ayant moins de formation. Nous rendons compte des enseignements d'un projet de démonstration visant à déterminer si des vaccinateurs étudiants profanes pourraient appuyer l'immunisation communautaire. INTERVENTION: Entre juillet 2022 et février 2023, 27 étudiantes et étudiants de premier cycle et de cycles supérieurs ont été recrutés auprès de l'organisation des secouristes opérationnels de l'Université de Toronto pour gérer 11 cliniques de vaccination sous la supervision de personnel spécialisé. Des directives médicales, appuyées par une formation en ligne et en présentiel, ont permis à ces prestataires profanes d'administrer des vaccins et de les consigner en dossier sous la supervision d'infirmières, de médecins ou de pharmaciens. Les personnes participantes ont été invitées à répondre à un sondage en ligne sur leur expérience. RéSULTATS: Les prestataires profanes ont administré 293 vaccins contre la grippe et la COVID-19 sans manifestations postvaccinales indésirables. En tout, 141 personnes (122 patients, 17 vaccinateurs profanes, 1 infirmière et 1 médecin) ont répondu au sondage. Plus de 80 % des patients ont dit se sentir tout à fait en sécurité et à l'aise de recevoir des vaccins administrés par des prestataires profanes sous supervision, n'avoir aucune inquiétude vis-à-vis des vaccinateurs profanes et être disposés à se présenter à une autre clinique gérée par des vaccinateurs profanes. L'analyse du contenu et des thèmes des réponses aux questions ouvertes a révélé des expériences majoritairement positives, et des thèmes axés sur l'excellence des vaccinateurs, l'organisation et l'efficacité des cliniques, ainsi que l'importance de la formation, des communications et de l'accès à des professionnels réglementés. Les prestataires ayant répondu au sondage se sont dit à l'aise de travailler au sein d'équipes de vaccination collaboratives. CONSéQUENCES: Des prestataires étudiants profanes peuvent administrer des vaccins en toute sécurité en suivant une directive médicale, et cela peut potentiellement améliorer l'expérience des patients. Plutôt que de redéployer des ressources professionnelles limitées, les stratégies de partage de tâches pourraient placer des vaccinateurs profanes formés pour appuyer l'immunisation, améliorer l'accès et favoriser l'engagement communautaire.

7.
J Food Prot ; 87(8): 100325, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38964610

ABSTRACT

With the emergence of clade 2.3.4.4b H5N1 highly pathogenic avian influenza virus (AIV) infection of dairy cattle and its subsequent detection in raw milk, coupled with recent AIV infections affecting dairy farm workers, experiments were conducted to affirm the safety of cooked ground beef related to AIV because such meat is often derived from cull dairy cows. Specifically, retail ground beef (percent lean:fat = ca. 80:20) was inoculated with a low pathogenic AIV (LPAIV) isolate to an initial level of 5.6 log10 50% egg infectious doses (EID50)  per 300 g patty. The inoculated meat was pressed into patties (ca. 2.54 cm thick, ca. 300 g each) and then held at 4 °C for up to 60 min. In each of the two trials, two patties for each of the following three treatments were cooked on a commercial open-flame gas grill to internal instantaneous temperatures of 48.9 °C (120°F), 62.8 °C (145°F), or 71.1 °C (160°F), but without any dwell time. Cooking inoculated ground beef patties to 48.9 °C (ave. cooking time of ca. 15 min) resulted in a mean reduction of ≥2.5 ± 0.9 log10 EID50 per 300 g of ground beef as assessed via quantification of virus in embryonating chicken eggs (ECEs). Likewise, cooking patties on a gas grill to 62.8 °C (ave. cooking time of ca. 21 min) or to the USDA FSIS recommended minimum internal temperature for ground beef of 71.1 °C (ave. cooking time of ca. 24 min) resulted in a reduction to nondetectable levels from initial levels of ≥5.6 log10 EID50 per 300 g. These data establish that levels of infectious AIV are substantially reduced within inoculated ground beef patties (20% fat) using recommended cooking procedures.

8.
Vaccine ; 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39013692

ABSTRACT

Influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are respiratory pathogens which significantly impact healthcare systems. Seasonal vaccination is recommended for all healthcare workers (HCWs) to reduce the risk for both operators and patients. Puglia, a region in Southern Italy, has been enforcing since 2018 a law mandating influenza vaccination in healthcare workers. However, vaccination coverages for this category have always been suboptimal. Our study tests the effectiveness of an active recall intervention on vaccination coverage for influenza and SARS-CoV-2 in the HCWs of a large Apulian hospital (Southern Italy). During the 2023-2024 influenza vaccination season, unvaccinated HCWs of Bari's Policlinico General Hospital were contacted. The e-mail reminded them of a regional law mandating influenza vaccination to all HCWs and offered an appointment for vaccination. SARS-CoV-2 vaccination was also offered. In 2022-2023, 43.16 % of HCWs were vaccinated against influenza and 21.87 % against SARS-CoV-2. Coverage changed during the 2023-2024 season to 54.11 % and 13.58 %, respectively. A regression model showed that vaccination uptake's increase was associated with the e-mail reception and with the operator being a physician vs. non-medical personnel. On the contrary, subjects who received the e-mail did not show an increased SARS-CoV-2 vaccination uptake, which was on the contrary influenced by the worker's age, sex, job title, and area of risk. Our soft-mandate intervention was effective in increasing vaccination uptake by HCWs. Communication with a trained specialist was probably useful, and the possibility to access vaccination services with dedicated appointments increased convenience. Mandatory vaccination policies and active recall seem to synergically impact vaccination uptake.

9.
Hum Vaccin Immunother ; 20(1): 2376821, 2024 Dec 31.
Article in English | MEDLINE | ID: mdl-39025479

ABSTRACT

Influenza vaccination is the most cost-effective strategy for influenza prevention. Influenza vaccines have been found to be effective against symptomatic and medically attended outpatient influenza illnesses. However, there is currently a lack of data regarding the effectiveness of inactivated influenza vaccines in Chongqing, China. We conducted a prospective observational test-negative design study. Outpatient and emergency cases presenting with influenza-like illnesses (ILI) and available influenza reverse transcription polymerase chain reaction (RT-PCR) were selected and classified as cases (positive influenza RT-PCR) or controls (negative influenza RT-PCR). A total of 7,307 cases of influenza and 7,905 control subjects were included in this study. The overall adjusted influenza vaccine effectiveness (IVE) was 44.4% (95% confidence interval (CI): 32.5-54.2%). In the age groups of less than 6 years old, 6-18 years old, and 19-59 years old, the adjusted IVE were 32.2% (95% CI: 10.0-48.9%), 48.2% (95% CI: 30.6-61.4%), and 72.0% (95% CI: 43.6-86.1%). The adjusted IVE for H1N1, H3N2 and B (Victoria) were 71.1% (95% CI: 55.4-81.3%), 36.1% (95% CI: 14.6-52.2%) and 33.7% (95% CI: 14.6-48.5%). Influenza vaccination was effective in Chongqing from 2018 to 2022. Evaluating IVE in this area is feasible and should be conducted annually in the future.


Subject(s)
Influenza Vaccines , Influenza, Human , Vaccine Efficacy , Humans , Influenza Vaccines/immunology , Influenza Vaccines/administration & dosage , China/epidemiology , Adolescent , Adult , Influenza, Human/prevention & control , Middle Aged , Young Adult , Child , Male , Female , Child, Preschool , Prospective Studies , Infant , Aged , Vaccination/statistics & numerical data , Vaccines, Inactivated/immunology , Vaccines, Inactivated/administration & dosage , Influenza A Virus, H3N2 Subtype/immunology , Influenza A Virus, H1N1 Subtype/immunology , Aged, 80 and over , Influenza B virus/immunology , Influenza B virus/genetics
10.
J Trop Pediatr ; 70(4)2024 Jul 13.
Article in English | MEDLINE | ID: mdl-39025514

ABSTRACT

OBJECTIVE: To identify the prevalence of respiratory syncytial virus (RSV) in a cohort of children under 5 years of age with World Health Organization (WHO)-defined pneumonia and the factors associated with developing severe RSV-associated community-acquired pneumonia (CAP) in primary care in a single centre in Northern Malawi. METHODS: The BIOmarkers TO diagnose PnEumonia (BIOTOPE) study was a prospective cohort study conducted from March to June 2016 that took place in a primary care centre in Northern Malawi. Data from this study was used to identify the characteristics of children under 5 years of age who presented with RSV and WHO-defined CAP. Means, standard deviations, medians and ranges were calculated for continuous variables. A univariate logistic regression was performed to examine the potential predictor variables. RESULTS: Four hundred and ninety-four infants presented with CAP and were eligible for inclusion in the study; RSV infection was detected in 205 (41.6%) of the infants. Eight factors were associated with increased risk for RSV CAP in the univariate model: age, born at term, presenting for care in June, crowded living environment, not being exclusively breastfed, not having received zinc or vitamin A supplementation in the last six months. Infants with RSV were more likely to have an oxygen saturation ≤92% compared to infants with other causes of pneumonia and more likely to have severe pneumonia as defined by the WHO. CONCLUSION: This study supports that RSV-associated CAP is linked to modifiable and non-modifiable risk factors; further research is indicated to determine which interventions would be most impactful. Developing and implementing an infant or maternal vaccine could be a cost-effective way to prevent RSV-associated CAP and mortality in developing nations. More research is needed to understand seasonal patterns of CAP and research over extended periods can offer valuable insights on host, environmental and pathogen-specific factors that contribute to RSV-associated CAP.


Subject(s)
Community-Acquired Infections , Primary Health Care , Respiratory Syncytial Virus Infections , Humans , Respiratory Syncytial Virus Infections/epidemiology , Respiratory Syncytial Virus Infections/diagnosis , Malawi/epidemiology , Male , Female , Infant , Prospective Studies , Community-Acquired Infections/epidemiology , Community-Acquired Infections/virology , Child, Preschool , Prevalence , Risk Factors , Respiratory Syncytial Virus, Human/isolation & purification , Infant, Newborn , Pneumonia/epidemiology , Pneumonia/virology , Pneumonia/diagnosis , Pneumonia, Viral/epidemiology , Pneumonia, Viral/diagnosis
11.
Open Forum Infect Dis ; 11(7): ofae355, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39015351

ABSTRACT

Background: In recent years, Vietnam has suffered multiple epizootics of influenza in poultry. Methods: From 10 January 2019 to 26 April 2021, we employed a One Health influenza surveillance approach at live bird markets (LBMs) and swine farms in Northern Vietnam. When the COVID-19 pandemic permitted, each month, field teams collected oral secretion samples from poultry and pigs, animal facility bioaerosol and fecal samples, and animal worker nasal washes at 4 LBMs and 5 swine farms across 5 sites. Initially samples were screened with molecular assays followed by culture in embryonated eggs (poultry swabs) or Madin-Darby canine kidney cells (human or swine swabs). Results: Many of the 3493 samples collected had either molecular or culture evidence for influenza A virus, including 314 (37.5%) of the 837 poultry oropharyngeal swabs, 144 (25.1%) of the 574 bioaerosol samples, 438 (34.9%) of the 1257 poultry fecal swab samples, and 16 (1.9%) of the 828 human nasal washes. Culturing poultry samples yielded 454 influenza A isolates, 83 of which were H5, and 70 (84.3%) of these were highly pathogenic. Additionally, a positive human sample had a H9N2 avian-like PB1 gene. In contrast, the prevalence of influenza A in the swine farms was much lower with only 6 (0.4%) of the 1700 total swine farm samples studied, having molecular evidence for influenza A virus. Conclusions: This study suggests that Vietnam's LBMs continue to harbor high prevalences of avian influenza A viruses, including many highly pathogenic H5N6 strains, which will continue to threaten poultry and humans.

12.
Virology ; 597: 110162, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38955082

ABSTRACT

There is an urgent need for influenza vaccines that offer broad cross-protection. The highly conserved ectodomain of the influenza matrix protein 2 (M2e) is a promising candidate; however, its low immunogenicity can be addressed. In this study, we developed influenza vaccines using the Lumazine synthase (LS) platform. The primary objective of this study was to determine the protective potential of M2e proteins expressed on Lumazine synthase (LS) nanoparticles. M2e-LS proteins, produced through the E. coli system, spontaneously assemble into nanoparticles. The study investigated the efficacy of the M2e-LS nanoparticle vaccine in mice. Mice immunized with M2e-LS nanoparticles exhibited significantly higher levels of intracellular cytokines than those receiving soluble M2e proteins. The M2e-LS protein exhibited robust immunogenicity and provided 100% protection against cross-clade influenza.


Subject(s)
Influenza A Virus, H1N1 Subtype , Influenza Vaccines , Multienzyme Complexes , Nanoparticles , Orthomyxoviridae Infections , Viral Matrix Proteins , Animals , Influenza Vaccines/immunology , Influenza Vaccines/administration & dosage , Influenza A Virus, H1N1 Subtype/immunology , Nanoparticles/chemistry , Viral Matrix Proteins/immunology , Viral Matrix Proteins/genetics , Viral Matrix Proteins/metabolism , Mice , Orthomyxoviridae Infections/prevention & control , Orthomyxoviridae Infections/immunology , Orthomyxoviridae Infections/virology , Multienzyme Complexes/immunology , Multienzyme Complexes/metabolism , Female , Mice, Inbred BALB C , Antibodies, Viral/immunology , Cytokines/metabolism , Cross Protection/immunology , Influenza, Human/prevention & control , Influenza, Human/immunology , Influenza, Human/virology , Escherichia coli/genetics , Escherichia coli/metabolism , Viroporin Proteins
13.
ACS Infect Dis ; 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-38970488

ABSTRACT

Low-pathogenic avian influenza virus (LPAIV) remains the most common subtype of type-A influenza virus that causes moderate to severe infection in poultry with significant zoonotic and pandemic potential. Due to high mutability, increasing drug resistance, and limited vaccine availability, the conventional means to prevent intra- or interspecies transmission of AIV is highly challenging. As an alternative to control AIV infections, cytokine-based approaches to augment antiviral host defense have gained significant attention. However, the selective application of cytokines is critical since unregulated expression of cytokines, particularly proinflammatory ones, can cause substantial tissue damage during acute phases of immune responses. Moreover, depending on the type of cytokine and its impact on intestinal microbiota, outcomes of cytokine-gut microflora interaction can have a critical effect on overall host defense against AIV infections. Our recent study demonstrated some prominent roles of chicken IL-17A (ChIL-17A) in regulating antiviral host responses against AIV infection, however, in an in vitro model. For more detailed insights into ChIL-17A function, in the present study, we investigated whether ChIL-17A-meditated elevated antiviral host responses can translate into effective immune protection against AIV infection in an in vivo system. Moreover, considering the role of gut health in fostering innate or local host responses, we further studied the contributory relationships between gut microbiota and host immunity against AIV infection in chickens. For this, we employed a recombinant lactic acid-producing bacterial (LAB) vector, Lactococcus lactis, expressing ChIL-17A and analyzed the in vivo functionality in chickens against an LPAIV (A/H9N2) infection. Our study delineates that mucosal delivery of rL. lactis expressing ChIL-17A triggers proinflammatory signaling cascades and can drive a positive shift in phylum Firmicutes, along with a marked decline in phylum Actinobacteriota and Proteobacteria, favoring effective antiviral host responses against AIV infection in chickens. We propose that ChIL-17A-mediated selective expansion of beneficial gut microbiota might form a healthy microbial community that augments the effective immune protection against AIV infections in chickens.

14.
Poult Sci ; 103(9): 103988, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38970848

ABSTRACT

Inactivated vaccines play an important role in preventing and controlling the epidemic caused by the H5 subtype avian influenza virus. The vaccine strains are updated in response to alterations in surface protein antigens, while an avian-derived vaccine internal backbone with a high replicative capacity in chicken embryonated eggs and MDCK cells is essential for vaccine development. In this study, we constructed recombinant viruses using the clade 2.3.4.4d A/chicken/Jiangsu/GY5/2017(H5N6, CkG) strain as the surface protein donor and the clade 2.3.4.4b A/duck/Jiangsu/84512/2017(H5N6, Dk8) strain with high replicative ability as an internal donor. After optimization, the integration of the M gene from the CkG into the internal genes from Dk8 (8GM) was selected as the high-yield vaccine internal backbone, as the combination improved the hemagglutinin1/nucleoprotein (HA1/NP) ratio in recombinant viruses. The r8GMΔG with attenuated hemagglutinin and neuraminidase from the CkG exhibited high-growth capacity in both chicken embryos and MDCK cell cultures. The inactivated r8GMΔG vaccine candidate also induced a higher hemagglutination inhibition antibody titer and microneutralization titer than the vaccine strain using PR8 as the internal backbone. Further, the inactivated r8GMΔG vaccine candidate provided complete protection against wild-type strain challenge. Therefore, our study provides a high-yield, easy-to-cultivate candidate donor as an internal gene backbone for vaccine development.

15.
Microbiol Spectr ; : e0115324, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38990032

ABSTRACT

Seasonal increase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza virus A/B (Flu A/B), and respiratory syncytial virus (RSV) require rapid diagnostic test methods for the management of respiratory tract infections. In this study, we compared the diagnostic accuracy of Savanna RVP4 (RVP4, QuidelOrtho) with Xpert Xpress Plus SARS-CoV-2/Flu/RSV (Xpert, Cepheid). Nasopharyngeal swabs from patients treated at a tertiary care hospital (Germany) were tested for SARS-CoV-2, Flu A/B, and RSV by RVP4 to assess diagnostic accuracy (reference standard: Xpert). The intra and inter assay precision of Ct-values was assessed by repeated test in triplicates (on day 1) and duplicates (days 2-3). All patients with a physician's order for a multiplex test for SARS-CoV-2, Flu, and RSV test were included. Duplicate swabs from the same patient, samples with a total volume ≤1 mL, or inappropriate shipment/storage were excluded. In total, 229 swabs were included between September 2023 and February 2024. The concordance between both tests was 96.5% (SARS-CoV-2), 98.7% (Flu A), and 99.6% (RSV). Flu B was not detected by both tests. The RVP4 test had a sensitivity of 85%-95% and a specificity of 100% for the detection of SARS-CoV-2, Flu A, and RSV. The intra and inter assay precision of Ct-values from RVP4 was 3% and 2% (SARS-CoV-2), 5% and 4% (Flu A), and 0% and 3% (RSV), respectively. The Savanna RVP4 has a favorable diagnostic accuracy for the detection of SARS-CoV-2, Flu A, and RSV. IMPORTANCE: We assessed the diagnostic accuracy of a new point-of-care test for the rapid detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza virus A/B (Flu A/B), and respiratory syncytial virus (RSV). The new test has a concordance with the reference standard of 96.5% (SARS-CoV-2), 98.7% (Flu A), and 99.1% (RSV). The sensitivity of 85%-95% and specificity of 100% for the detection of SARS-CoV-2, Flu A, and RSV is comparable with similar nucleic acid amplification-based point of care tests but at lower costs.

16.
Hum Vaccin Immunother ; 20(1): 2370087, 2024 Dec 31.
Article in English | MEDLINE | ID: mdl-38982712

ABSTRACT

The immune response to inactivated influenza vaccines (IIV) is influenced by multiple factors, including hemagglutinin content and egg-based manufacturing. Only two US-licensed vaccines are manufactured without egg passage: cell culture-based inactivated vaccine (ccIIV) and recombinant vaccine (RIV). We conducted a randomized open-label trial in central Wisconsin during the 2018-19 and 2019-20 seasons to compare immunogenicity of sequential vaccination. Participants 18-64 years old were randomized 1:1:1 to receive RIV, ccIIV or IIV in strata defined by number of influenza vaccine doses in the prior 3 years. They were revaccinated with the same product in year two. Paired serum samples were tested by hemagglutination inhibition against egg-adapted and cell-grown vaccine viruses. Serologic endpoints included geometric mean titer (GMT), mean fold rise, and percent seroconversion. There were 373 participants randomized and vaccinated in 2018-19; 332 were revaccinated in 2019-20. In 2018-19, RIV and ccIIV were not more immunogenic than IIV against A/H1N1. The post-vaccination GMT against the cell-grown 3C.2a A/H3N2 vaccine virus was higher for RIV vs IIV (p = .001) and RIV vs ccIIV (p = .001). The antibody response to influenza B viruses was similar across study arms. In 2019-20, GMT against the cell-grown 3C.3a A/H3N2 vaccine virus was higher for RIV vs IIV (p = .03) and for RIV vs ccIIV (p = .001). RIV revaccination generated significantly greater backboosting to the antigenically distinct 3C.2a A/H3N2 virus (2018-19 vaccine strain) compared to ccIIV or IIV. This study adds to the evidence that RIV elicits a superior immunologic response against A/H3N2 viruses compared to other licensed influenza vaccine products.


Subject(s)
Antibodies, Viral , Hemagglutination Inhibition Tests , Influenza A Virus, H1N1 Subtype , Influenza Vaccines , Influenza, Human , Vaccines, Inactivated , Vaccines, Synthetic , Humans , Influenza Vaccines/immunology , Influenza Vaccines/administration & dosage , Adult , Antibodies, Viral/blood , Young Adult , Influenza, Human/prevention & control , Influenza, Human/immunology , Female , Male , Middle Aged , Vaccines, Inactivated/immunology , Vaccines, Inactivated/administration & dosage , Adolescent , Influenza A Virus, H1N1 Subtype/immunology , Vaccines, Synthetic/immunology , Vaccines, Synthetic/administration & dosage , Influenza A Virus, H3N2 Subtype/immunology , Wisconsin , Vaccination/methods , Influenza B virus/immunology , Immunogenicity, Vaccine , Cell Culture Techniques , United States , Antibody Formation/immunology , Immunization, Secondary/methods , Eggs
17.
Antiviral Res ; 229: 105959, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38986873

ABSTRACT

Avian influenza outbreaks, including ones caused by highly pathogenic A(H5N1) clade 2.3.4.4b viruses, have devastated animal populations and remain a threat to humans. Risk elements assessed for emerging influenza viruses include their susceptibility to approved antivirals. Here, we screened >20,000 neuraminidase (NA) or polymerase acidic (PA) protein sequences of potentially pandemic A(H5Nx), A(H7Nx), and A(H9N2) viruses that circulated globally in 2010-2023. The frequencies of NA or PA substitutions associated with reduced inhibition (RI) or highly reduced inhibition (HRI) by NA inhibitors (NAIs) (oseltamivir, zanamivir) or a cap-dependent endonuclease inhibitor (baloxavir) were low: 0.60% (137/22,713) and 0.62% (126/20,347), respectively. All tested subtypes were susceptible to NAIs and baloxavir at sub-nanomolar concentrations. A(H9N2) viruses were the most susceptible to oseltamivir, with IC50s 3- to 4-fold lower than for other subtypes (median IC50: 0.18 nM; n = 22). NA-I222M conferred RI of A(H5N1) viruses by oseltamivir (with a 26-fold IC50 increase), but NA-S246N did not reduce inhibition. PA-E23G, PA-K34R, PA-I38M/T, and the previously unreported PA-A36T caused RI by baloxavir in all subtypes tested. Avian A(H9N2) viruses endemic in Egyptian poultry predominantly acquired PA-I38V, which causes only a <3-fold decrease in the baloxavir EC50 and fails to meet the RI criteria. PA-E199A/D in A(H7Nx) and A(H9N2) viruses caused a 2- to 4-fold decrease in EC50 (close to the borderline for RI) and should be closely monitored. Our data indicate antiviral susceptibility is high among avian influenza A viruses with pandemic potential and present novel markers of resistance to existing antiviral interventions.

18.
Sci Rep ; 14(1): 15853, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38982082

ABSTRACT

Influenza (Flu) is a severe health, medical, and economic problem, but no medication that has excellent outcomes and lowers the occurrence of these problems is now available. GanghuoQingwenGranules (GHQWG) is a common Chinese herbal formula for the treatment of influenza (flu). However, its methods of action remain unknown. We used network pharmacology, molecular docking, and molecular dynamics simulation techniques to investigate the pharmacological mechanism of GHQWG in flu. TCMSP and various types of literature were used to obtain active molecules and targets of GHQWG. Flu-related targets were found in the Online Mendelian Inheritance in Man (OMIM) database, the DisFeNET database, the Therapeutic Target Database (TTD), and the DrugBank database. To screen the key targets, a protein-protein interaction (PPI) network was constructed. DAVID was used to analyze GO and KEGG pathway enrichment. Target tissue and organ distribution was assessed. Molecular docking was used to evaluate interactions between possible targets and active molecules. For the ideal core protein-compound complexes obtained using molecular docking, a molecular dynamics simulation was performed. In total, 90 active molecules and 312 GHQWG targets were discovered. The PPI network's topology highlighted six key targets. GHQWG's effects are mediated via genes involved in inflammation, apoptosis, and oxidative stress, as well as the TNF and IL-17 signaling pathways, according to GO and KEGG pathway enrichment analysis. Molecular docking and molecular dynamics simulations demonstrated that the active compounds and tested targets had strong binding capabilities. This analysis accurately predicts the effective components, possible targets, and pathways involved in GHQWG flu treatment. We proposed a novel study strategy for future studies on the molecular processes of GHQWG in flu treatment. Furthermore, the possible active components provide a dependable source for flu drug screening.


Subject(s)
Drugs, Chinese Herbal , Influenza, Human , Molecular Docking Simulation , Molecular Dynamics Simulation , Network Pharmacology , Protein Interaction Maps , Humans , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Influenza, Human/drug therapy , Influenza, Human/virology , Protein Interaction Maps/drug effects , Antiviral Agents/pharmacology , Antiviral Agents/chemistry , Antiviral Agents/therapeutic use
19.
Emerg Microbes Infect ; 13(1): 2368202, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38970562

ABSTRACT

Influenza A viruses (IAV) impose significant respiratory disease burdens in both swine and humans worldwide, with frequent human-to-swine transmission driving viral evolution in pigs and highlighting the risk at the animal-human interface. Therefore, a comprehensive One Health approach (interconnection among human, animal, and environmental health) is needed for IAV prevention, control, and response. Animal influenza genomic surveillance remains limited in many Latin American countries, including Colombia. To address this gap, we genetically characterized 170 swine specimens from Colombia (2011-2017). Whole genome sequencing revealed a predominance of pandemic-like H1N1 lineage, with a minority belonging to H3N2 and H1N2 human seasonal-like lineage and H1N1 early classical swine lineages. Significantly, we have identified reassortant and recombinant viruses (H3N2, H1N1) not previously reported in Colombia. This suggests a broad genotypic viral diversity, likely resulting from reassortment between classical endemic viruses and new introductions established in Colombia's swine population (e.g. the 2009 H1N1 pandemic). Our study highlights the importance of a One Health approach in disease control, particularly in an ecosystem where humans are a main source of IAV to swine populations, and emphasizes the need for continued surveillance and enhanced biosecurity measures. The co-circulation of multiple subtypes in regions with high swine density facilitates viral exchange, underscoring the importance of monitoring viral evolution to inform vaccine selection and public health policies locally and globally.


Subject(s)
Evolution, Molecular , Genetic Variation , Influenza A Virus, H1N1 Subtype , Influenza A Virus, H3N2 Subtype , Orthomyxoviridae Infections , Phylogeny , Swine Diseases , Animals , Swine , Colombia/epidemiology , Orthomyxoviridae Infections/virology , Orthomyxoviridae Infections/veterinary , Orthomyxoviridae Infections/epidemiology , Swine Diseases/virology , Swine Diseases/epidemiology , Influenza A Virus, H3N2 Subtype/genetics , Influenza A Virus, H3N2 Subtype/classification , Influenza A Virus, H3N2 Subtype/isolation & purification , Influenza A Virus, H1N1 Subtype/genetics , Influenza A Virus, H1N1 Subtype/classification , Influenza A Virus, H1N1 Subtype/isolation & purification , One Health , Humans , Influenza A virus/genetics , Influenza A virus/classification , Influenza A virus/isolation & purification , Whole Genome Sequencing , Genome, Viral , Epidemiological Monitoring , Reassortant Viruses/genetics , Reassortant Viruses/classification , Reassortant Viruses/isolation & purification , Influenza A Virus, H1N2 Subtype/genetics , Influenza A Virus, H1N2 Subtype/isolation & purification , Influenza A Virus, H1N2 Subtype/classification , Influenza, Human/virology , Influenza, Human/epidemiology
20.
Hum Vaccin Immunother ; 20(1): 2364480, 2024 Dec 31.
Article in English | MEDLINE | ID: mdl-38972854

ABSTRACT

Elderly individuals face a high risk of hospitalization and death related to influenza, thus prioritizing them for influenza vaccination. Due to variations in the influenza virus and waning protective antibodies, annual influenza vaccination is recommended. However, research on repeated influenza vaccination among elderly individuals in China is limited. From 2020 to 2022, the average influenza vaccination coverage among registered elderly individuals in Shanghai was 4.1%, showing a declining trend over time. In 2020, the rate of repeated influenza vaccination among elderly individuals was 28.35%, which rose to almost two-thirds both in 2021 and 2022. No increased risk of adverse events following immunization was observed after repeated influenza vaccination during this period. Our study also found that elderly individuals with Shanghai household registration, managed by community clinics, and older age tended to receive more doses of repeated influenza vaccination throughout the period from 2020 to 2022. Increasing influenza vaccine coverage among elderly individuals in Shanghai is both urgent and challenging. Health authorities should intensify educational and promotional campaigns to encourage uptake of annual repeated influenza vaccination among elderly individuals.


Subject(s)
Influenza Vaccines , Influenza, Human , Vaccination Coverage , Humans , China , Influenza Vaccines/administration & dosage , Aged , Influenza, Human/prevention & control , Male , Female , Vaccination Coverage/statistics & numerical data , Vaccination Coverage/trends , Aged, 80 and over , Vaccination/statistics & numerical data , Vaccination/trends , Middle Aged
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