Zoonotic transmission of novel Influenza A variant viruses detected in Brazil during 2020 to 2023.

Zoonotic infections (swine-human) caused by influenza A viruses (IAVs) have been reported and linked to close contact between these species. Here, we describe eight human IAV variant infections (6 mild and 2 severe cases, including 1 death) detected in Paraná, Brazil, during 2020-2023. Genomes recovered were closely related to Brazilian swIAVs of three major lineages (1 A.3.3.2/pdm09, 1B/human-like, and H3.1990.5), including three H1N1v, two H1N2v, two H3N2v and one H1v. Five H1v were closely related to pdm09 lineage, one H1v (H1N2v) grouped within 1B.2.3 clade, and the two H3v grouped within a clade composed exclusively of Brazilian H3 swIAV (clade H3.1990.5.1). Internal gene segments were closely related to H1N1pdm09 isolated from pigs. IAV variant rarely result in sustained transmission between people, however the potential to develop such ability is of concern and must not be underestimated. This study brings into focus the need for continuous influenza surveillance and timely risk assessment.

Interim Effectiveness Estimates of 2024 Southern Hemisphere Influenza Vaccines in Preventing Influenza-Associated Hospitalization - REVELAC-i Network, Five South American Countries, March-July 2024.

To reduce influenza-associated morbidity and mortality, countries in South America recommend annual influenza vaccination for persons at high risk for severe influenza illness, including young children, persons with preexisting health conditions, and older adults. Interim estimates of influenza vaccine effectiveness (VE) from Southern Hemisphere countries can provide early information about the protective effects of vaccination and help guide Northern Hemisphere countries in advance of their season. Using data from a multicountry network, investigators estimated interim VE against influenza-associated severe acute respiratory illness (SARI) hospitalization using a test-negative case-control design. During March 13-July 19, 2024, Argentina, Brazil, Chile, Paraguay, and Uruguay identified 11,751 influenza-associated SARI cases; on average, 21.3% of patients were vaccinated against influenza, and the adjusted VE against hospitalization was 34.5%. The adjusted VE against the predominating subtype A(H3N2) was 36.5% and against A(H1N1)pdm09 was 37.1%. These interim VE estimates suggest that although the proportion of hospitalized patients who were vaccinated was modest, vaccination with the Southern Hemisphere influenza vaccine significantly lowered the risk for hospitalization. Northern Hemisphere countries should, therefore, anticipate the need for robust influenza vaccination campaigns and early antiviral treatment to achieve optimal protection against influenza-associated complications.

Treatment with lipoxin A4 improves influenza A infection outcome, induces macrophage reprogramming, anti-inflammatory and pro-resolutive responses.

INTRODUCTION: Influenza A is a virus from the Orthomixoviridae family responsible for high lethality rates and morbidity, despite clinically proven vaccination strategies and some anti-viral therapies. The eicosanoid Lipoxin A4 (LXA4) promotes the resolution of inflammation by decreasing cell recruitment and pro-inflammatory cytokines release, but also for inducing activation of apoptosis, efferocytosis, and macrophage reprogramming. OBJECTIVE: Here, we evaluated whether a synthetic lipoxin mimetic, designated AT-01-KG, would improve the course of influenza A infection in a murine model. METHOD: Mice were infected with influenza A/H1N1 and treated with AT-01-KG (1.7 µg/kg/day, i.p.) at day 3 post-infection. RESULTS: AT-01-KG attenuated mortality, reducing leukocyte infiltration and lung damage at day 5 and day 7 post-infection. AT-01-KG is a Formyl Peptide Receptor 2 (designated FPR2/3 in mice) agonist, and the protective responses were not observed in fpr2/3 -/- animals. In mice treated with LXA4 (50 µg/kg/day, i.p., days 3-6 post-infection), at day 7, macrophage reprogramming was observed, as seen by a decrease in classically activated macrophages and an increase in alternatively activated macrophages in the lungs. Furthermore, the number of apoptotic cells and cells undergoing efferocytosis was increased in the lavage of treated mice. Treatment also modulated the adaptive immune response, increasing the number of T helper 2 cells (Th2) and regulatory T (Tregs) cells in the lungs of the treated mice. CONCLUSION: Therefore, treatment with a lipoxin A4 analog was beneficial in a model of influenza A infection in mice. The drug decreased inflammation and promoted resolution and beneficial immune responses, suggesting it may be useful in patients with severe influenza.

Biological, social, and healthcare factors for death due to influenza A(H1N1) during the 2009 epidemic in Brazil.

OBJECTIVE: To identify risk factors for death from influenza A(H1N1), including the effectiveness of the vaccine against influenza A(H1N1) concerning mortality. METHODS: A case-control of incident cases of influenza A(H1N1) reported in the epidemiological information systems of the states of São Paulo, Paraná, Pará, Amazonas, and Rio Grande do Sul was conducted. RESULTS: 305 participants were included, 70 of them cases and 235 controls, distributed as follows: Amazonas, 9 cases/10 controls; Pará, 22 cases/77 controls, São Paulo, 19 cases/49 controls; Paraná, 10 cases/54 controls; Rio Grande do Sul, 10 cases/45 controls. These participants had a mean age of 30 years, with 33 years among cases and 25 years among controls. There was a predominance of females both among the cases and controls. Biological (age), pre-existing diseases (congestive heart failure, respiratory disease, and diabetes mellitus), and care factors (ICU admission) associated with death from influenza A(H1N1) were identified. CONCLUSION: The risk factors identified in this investigation not only allowed subsidizing the elaboration of clinical conducts but also indicate important aspects for facing "new" influenza epidemics that are likely to occur in our country.

Genomic diversity and evolutionary dynamics of Influenza A viruses in Colombian swine: implications for one health surveillance and control.

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.

Anti-hemagglutinin monomeric nanobody provides prophylactic immunity against H1 subtype influenza A viruses.

Influenza viruses constitute a major threat to human health globally. The viral surface glycoprotein hemagglutinin (HA) is the immunodominant antigen, contains the site for binding to the cellular receptor (RBS), and it is the major target of neutralizing antibody responses post-infection. We developed llama-derived single chain antibody fragments (VHHs) specific for type A influenza virus. Four VHHs were identified and further characterized. VHH D81 bound residues in the proximity of the C-terminal region of HA1 of H1 and H5 subtypes, and showed weak neutralizing activity, whereas VHH B33 bound residues in the proximity of the N-terminal region of the HA's stem domain (HA2) of H1, H5, and H9 subtypes, and showed no neutralizing activity. Of most relevance, VHHs E13 and G41 recognized highly conserved conformational epitopes on the H1 HA's globular domain (HA1) and showed high virus neutralizing activity (ranging between 0.94 to 0.01µM), when tested against several human H1N1 isolates. Additionally, E13 displayed abrogated virus replication of a panel of H1N1 strains spanning over 80 years of antigenic drift and isolated from human, avian, and swine origin. Interestingly, E13 conferred protection in vivo at a dose as low as 0.05 mg/kg. Mice treated with E13 intranasally resulted in undetectable virus challenge loads in the lungs at day 4 post-challenge. The transfer of sterilizing pan-H1 immunity, by a dose in the range of micrograms given intranasally, is of major significance for a monomeric VHH and supports the further development of E13 as an immunotherapeutic agent for the mitigation of influenza infections.

Insights into the association of H1N1 seasonality with the COVID-19 pandemic in Brazil: an ecological time series analysis.

During the COVID-19 pandemic, H1N1 seasonality disappeared worldwide. In Brazil, information on how coronavirus impacted this seasonality is scarce. In this study, we aimed to verify whether COVID-19 pandemic was associated with changes in the seasonality of H1N1, modeling the time series of H1N1 between pre-pandemic (2018 and 2019), pandemic (2020 and 2021) and post-pandemic (2022 and 2023) periods. For this purpose, we superimposed on this time series cases of COVID-19 from 2020 to 2023. Our findings highlighted that H1N1 exhibited a consistent seasonal pattern in the pre-pandemic period, with peaks mainly in months with the highest rainfall. However, this seasonality disappeared during the pandemic, with a significant decrease in the number of cases, in contrast with the predicted seasonality of H1N1 for the same period. In addition, the seasonal pattern of H1N1 in the post-pandemic showed a return to that observed in the pre-pandemic period, especially in 2023. We observed that the COVID-19 pandemic was consistently associated with changes in H1N1 seasonality in Brazil, underscoring the relative importance of monitoring patterns of respiratory syndromes to enhance our understanding of how coronavirus is associated with changes in seasonal diseases.

Low antiviral resistance in Influenza A and B viruses isolated in Mexico from 2010 to 2023.

The most widely used class of antivirals available for Influenza treatment are the neuraminidase inhibitors (NAI) Oseltamivir and Zanamivir. However, amino acid (AA) substitutions in the neuraminidase may cause reduced inhibition or high antiviral resistance. In Mexico, the current state of knowledge about NAI susceptibility is scarce, in this study we report the results of 14 years of Influenza surveillance by phenotypic and genotypic methods. A total of 255 isolates were assessed with the NAI assay, including Influenza A(H1N1)pdm09, A(H3N2) and Influenza B (IBV). Furthermore, 827 sequences contained in the GISAID platform were analyzed in search of relevant mutations.Overall, five isolates showed highly reduced inhibition or reduced inhibition to Oseltamivir, and two showed reduced inhibition to Zanamivir in the NAI assays. Additionally, five A(H1N1)pdm09 sequences from the GISAID possessed AA substitutions associated to reduced inhibition to Oseltamivir and none to Zanamivir. Oseltamivir resistant A(H1N1)pdm09 harbored the H275Y mutation. No genetic mutations were identified in Influenza A(H3N2) and IBV. Overall, these results show that in Mexico the rate of NAI resistance is low (0.6%), but it is essential to continue the Influenza surveillance in order to understand the drug susceptibility of circulating strains.

Detection and Characterization of Influenza A Virus Endemic Circulation in Suckling and Nursery Pigs Originating from Vaccinated Farms in the Same Production System.

Inactivated influenza A virus (IAV) vaccines help reduce clinical disease in suckling piglets, although endemic infections still exist. The objective of this study was to evaluate the detection of IAV in suckling and nursery piglets from IAV-vaccinated sows from farms with endemic IAV infections. Eight nasal swab collections were obtained from 135 two-week-old suckling piglets from four farms every other week from March to September 2013. Oral fluid samples were collected from the same group of nursery piglets. IAV RNA was detected in 1.64% and 31.01% of individual nasal swabs and oral fluids, respectively. H1N2 was detected most often, with sporadic detection of H1N1 and H3N2. Whole-genome sequences of IAV isolated from suckling piglets revealed an H1 hemagglutinin (HA) from the 1B.2.2.2 clade and N2 neuraminidase (NA) from the 2002A clade. The internal gene constellation of the endemic H1N2 was TTTTPT with a pandemic lineage matrix. The HA gene had 97.59% and 97.52% nucleotide and amino acid identities, respectively, to the H1 1B.2.2.2 used in the farm-specific vaccine. A similar H1 1B.2.2.2 was detected in the downstream nursery. These data demonstrate the low frequency of IAV detection in suckling piglets and downstream nurseries from farms with endemic infections in spite of using farm-specific IAV vaccines in sows.

Novel influenza A viruses in pigs with zoonotic potential, Chile.

Novel H1N2 and H3N2 swine influenza A viruses (IAVs) have recently been identified in Chile. The objective of this study was to evaluate their zoonotic potential. We perform phylogenetic analyses to determine the genetic origin and evolution of these viruses, and a serological analysis to determine the level of cross-protective antibodies in the human population. Eight genotypes were identified, all with pandemic H1N1 2009-like internal genes. H1N1 and H1N2 were the subtypes more commonly detected. Swine H1N2 and H3N2 IAVs had hemagglutinin and neuraminidase lineages genetically divergent from IAVs reported worldwide, including human vaccine strains. These genes originated from human seasonal viruses were introduced into the swine population since the mid-1980s. Serological data indicate that the general population is susceptible to the H3N2 virus and that elderly and young children also lack protective antibodies against the H1N2 strains, suggesting that these viruses could be potential zoonotic threats. Continuous IAV surveillance and monitoring of the swine and human populations is strongly recommended.IMPORTANCEIn the global context, where swine serve as crucial intermediate hosts for influenza A viruses (IAVs), this study addresses the pressing concern of the zoonotic potential of novel reassortant strains. Conducted on a large scale in Chile, it presents a comprehensive account of swine influenza A virus diversity, covering 93.8% of the country's industrialized swine farms. The findings reveal eight distinct swine IAV genotypes, all carrying a complete internal gene cassette of pandemic H1N1 2009 origin, emphasizing potential increased replication and transmission fitness. Genetic divergence of H1N2 and H3N2 IAVs from globally reported strains raises alarms, with evidence suggesting introductions from human seasonal viruses since the mid-1980s. A detailed serological analysis underscores the zoonotic threat, indicating susceptibility in the general population to swine H3N2 and a lack of protective antibodies in vulnerable demographics. These data highlight the importance of continuous surveillance, providing crucial insights for global health organizations.

Clinical predictors of severe forms of influenza A(H1N1)pdm09 in adults and children during the 2009 epidemic in Brazil.

The World Health Organization (WHO) raised the global alert level for the A(H1N1) influenza pandemic in June 2009. However, since the beginning of the epidemic, the fight against the epidemic lacked foundations for managing cases to reduce the disease lethality. It was urgent to carry out studies that would indicate a model for predicting severe forms of influenza. This study aimed to identify risk factors for severe forms during the 2009 influenza epidemic and develop a prediction model based on clinical epidemiological data. A case-control of cases notified to the health secretariats of the states of Rio de Janeiro, São Paulo, Minas Gerais, Paraná, and Rio Grande do Sul was conducted. Cases had fever, respiratory symptoms, positive confirmatory test for the presence of the virus associated with one of the three conditions: (i) presenting respiratory complications such as pneumonia, ventilatory failure, severe acute respiratory distress syndrome, sepsis, acute cardiovascular complications or death; or respiratory failure requiring invasive or non-invasive ventilatory support, (ii) having been hospitalized or (iii) having been admitted to an Intensive Care Unit. Controls were individuals diagnosed with the disease on the same date (or same week) as the cases. A total of 1653 individuals were included in the study, (858 cases/795 controls). These participants had a mean age of 26 years, a low level of education, and were mostly female. The most important predictors identified were systolic blood pressure in mmHg, respiratory rate in bpm, dehydration, obesity, pregnancy (in women), and vomiting (in children). Three clinical prediction models of severity were developed, for adults, adult women, and for children. The performance evaluation of these models indicated good predictive capacity. The area values under the ROC curve of these models were 0.89; 0.98 and 0.91 respectively for the model of adults, adult women, and children respectively.

Influenza A virus antibodies in dogs, hunting dogs, and backyard pigs in Campeche, Mexico.

AIMS: This study aimed to identify exposure to human, swine, and avian influenza A virus subtypes in rural companion and hunting dogs, backyard pigs, and feral pigs. METHODS AND RESULTS: The study took place in a region of southeastern Mexico where the sampled individuals were part of backyard production systems in which different domestic and wild species coexist and interact with humans. We collected blood samples from pigs and dogs at each of the sites. We used a nucleoprotein enzyme-linked immunosorbent assay to determine the exposure of individuals to influenza A virus. Haemagglutination inhibition was performed on the positive samples to determine the subtypes to which they were exposed. For data analysis, a binomial logistic regression model was generated to determine the predictor variables for the seropositivity of the individuals in the study. We identified 11 positive individuals: three backyard pigs, four companion dogs, and four hunting dogs. The pigs tested positive for H1N1 and H1N2. The dogs were positive for H1N1, H1N2, and H3N2. The model showed that dogs in contact with backyard chickens are more likely to be seropositive for influenza A viruses. CONCLUSIONS: We demonstrated the essential role hunting dogs could play as intermediate hosts and potential mixing vessel hosts when exposed to human and swine-origin viral subtypes. These results are relevant because these dogs interact with domestic hosts and humans in backyard systems, which are risk scenarios in the transmission of influenza A viruses. Therefore, it is of utmost importance to implement epidemiological surveillance of influenza A viruses in backyard animals, particularly in key animals in the transmission of these viruses, such as dogs and pigs.

Combining Digital and Molecular Approaches Using Health and Alternate Data Sources in a Next-Generation Surveillance System for Anticipating Outbreaks of Pandemic Potential.

Globally, millions of lives are impacted every year by infectious diseases outbreaks. Comprehensive and innovative surveillance strategies aiming at early alert and timely containment of emerging and reemerging pathogens are a pressing priority. Shortcomings and delays in current pathogen surveillance practices further disturbed informing responses, interventions, and mitigation of recent pandemics, including H1N1 influenza and SARS-CoV-2. We present the design principles of the architecture for an early-alert surveillance system that leverages the vast available data landscape, including syndromic data from primary health care, drug sales, and rumors from the lay media and social media to identify areas with an increased number of cases of respiratory disease. In these potentially affected areas, an intensive and fast sample collection and advanced high-throughput genome sequencing analyses would inform on circulating known or novel pathogens by metagenomics-enabled pathogen characterization. Concurrently, the integration of bioclimatic and socioeconomic data, as well as transportation and mobility network data, into a data analytics platform, coupled with advanced mathematical modeling using artificial intelligence or machine learning, will enable more accurate estimation of outbreak spread risk. Such an approach aims to readily identify and characterize regions in the early stages of an outbreak development, as well as model risk and patterns of spread, informing targeted mitigation and control measures. A fully operational system must integrate diverse and robust data streams to translate data into actionable intelligence and actions, ultimately paving the way toward constructing next-generation surveillance systems.

Influenza A infections: predictors of disease severity.

Influenza affects approximately 10% of the world's population annually. It is associated with high morbidity and mortality rates due to its propensity to progress to severe acute respiratory infection, leading to 10-40% of hospitalized patients needing intensive care. Characterizing the multifactorial predictors of poor prognosis is essential for developing strategies against this disease. This study aimed to identify predictors of disease severity in influenza A-infected (IFA-infected) patients and to propose a prognostic score. A retrospective cross-sectional study was conducted with 142 IFA-infected out- and inpatients treated at a tertiary hospital between 2010 and 2018. The viral subtypes, hemagglutinin mutations, viral load, IL-28B SNPs, and clinical risk factors were evaluated according to the patient's ICU admission. Multivariate analysis identified the following risk factors for disease severity: neuromuscular diseases (OR = 7.02; 95% CI = 1.18-41.75; p = 0.032), cardiovascular diseases (OR = 5.47; 95% CI = 1.96-15.27; p = 0.001), subtype (H1N1) pdm09 infection (OR = 2.29; 95% CI = 1.02-5.15; p = 0.046), and viral load (OR = 1.43; 95% CI = 1.09-1.88; p = 0.009). The prognosis score for ICU admission is based on these predictors of severity presented and ROC curve AUC = 0.812 (p < 0.0001). Our results identified viral and host predictors of disease severity in IFA-infected patients, yielding a prognostic score that had a high performance in predicting the IFA patients' ICU admission and better results than a viral load value alone. However, its implementation in health services needs to be validated in a broader population.

Rabdomiólise secundária à infecção pelo vírus Influenza / Rhabdomyolysis secondary to influenza virus infection

A rabdomiólise é uma condição potencialmente grave que pode resultar, dentre outros, da infecção por Influenza. Relatamos o caso de um jovem de 32 anos, sem comorbidades, o qual apresentou febre, mialgia e urina escurecida há quatro dias, seguidas de tosse e coriza. Os exames mostraram elevação significativa da creatinofosfoquinase (64.617U/L) e das transaminases. As principais hipóteses diagnósticas para justificar o quadro foram de etiologia infecciosa, em especial a leptospirose e hepatite viral aguda, antes da confirmação específica da infecção por Influenza A e B. Além de ter sido medicado com ceftriaxona por 10 dias, o paciente recebeu vigorosa e precoce hidratação intravenosa ­ fator que contribuiu, com certeza, para a boa evolução clínica e laboratorial, sem desenvolver lesão renal.

Biological, social, and healthcare factors for death due to influenza A(H1N1) during the 2009 epidemic in Brazil

ABSTRACT OBJECTIVE To identify risk factors for death from influenza A(H1N1), including the effectiveness of the vaccine against influenza A(H1N1) concerning mortality. METHODS A case-control of incident cases of influenza A(H1N1) reported in the epidemiological information systems of the states of São Paulo, Paraná, Pará, Amazonas, and Rio Grande do Sul was conducted. RESULTS 305 participants were included, 70 of them cases and 235 controls, distributed as follows: Amazonas, 9 cases/10 controls; Pará, 22 cases/77 controls, São Paulo, 19 cases/49 controls; Paraná, 10 cases/54 controls; Rio Grande do Sul, 10 cases/45 controls. These participants had a mean age of 30 years, with 33 years among cases and 25 years among controls. There was a predominance of females both among the cases and controls. Biological (age), pre-existing diseases (congestive heart failure, respiratory disease, and diabetes mellitus), and care factors (ICU admission) associated with death from influenza A(H1N1) were identified. CONCLUSION The risk factors identified in this investigation not only allowed subsidizing the elaboration of clinical conducts but also indicate important aspects for facing "new" influenza epidemics that are likely to occur in our country.

Comparative analysis of Respiratory Syncytial Virus frequency rates and viral load in different patient cohorts in a University Hospital in São Paulo, Brazil, over an eight-year period (2005-2013).

Respiratory Syncytial Virus (RSV) poses a global health concern, particularly affecting young children, the elderly, and immunosuppressed individuals. RSV viral load is essential for understanding transmission, disease severity, prevention, and treatment. This retrospective study aimed to analyze the frequency rates and viral loads of RSV infections in different patient cohorts and age groups over an eight-year period in a university hospital in São Paulo, Brazil. This study analyzed 1380 Immunocompetent (IC) and Immunosuppressed (IS) patients with acute respiratory tract infections. IC included patients with chronic Heart Disease (HD), Primary Care service recipients (PC), and a subgroup suspected of having Severe Acute Respiratory Syndrome caused by Influenza A (H1N1)pdm09 virus (SARS H1N1). IS comprised transplant patients and those with HIV infection. Respiratory samples were collected between February 2005 and October 2013, with RSV detection and viral load quantification (Log10 copies of RNA/mL) using RT-qPCR. Overall RSV infection rate was 17.3 %, with higher rates in children (23.9 %) than in adults (12.9 %), particularly in children under two years of age (28.2 %). Children in the SARS H1N1 and PC subgroups had higher infection rates (16.4 % and 34.9 %, respectively), with the highest rate in PC children aged 1 to < 2 years (45.45 %). Adults with HD had a significantly higher frequency rate (27.83 %) than those in the SARS H1N1 (2.65 %) and IS (15.16 %) subgroups and higher hospitalization rate among adults under 65 years. RSV viral load ranged from 2.43 to 10.15 Log10 RNA copies/mL (mean ± SD 5.82 ± 2.19), with hospitalized patients exhibiting significantly higher viral loads (7.34 ± 1.9) than outpatients (4.38 ± 1.89). Elderly bone marrow transplant patients also had significantly higher viral loads (7.57 ± 2.41) than younger adults (5.12 ± 1.87). This study provides insights into the RSV infection patterns in different patient cohorts in Brazil. Further investigations are needed to understand susceptibility and risk factors associated with RSV infection. In conclusion, high RSV viral load among hospitalized patients could serve as a surrogate marker of disease severity. Additionally, patients with chronic heart disease deserve greater attention regarding complications associated with RSV infection.

Safety and immunogenicity of influenza A(H3N2) component vaccine in juvenile systemic lupus erythematosus.

INTRODUCTION: Seasonal influenza A (H3N2) virus is an important cause of morbidity and mortality in the last 50 years in population that is greater than the impact of H1N1. Data assessing immunogenicity and safety of this virus component in juvenile systemic lupus erythematosus (JSLE) is lacking in the literature. OBJECTIVE: To evaluate short-term immunogenicity and safety of influenza A/Singapore (H3N2) vaccine in JSLE. METHODS: 24 consecutive JSLE patients and 29 healthy controls (HC) were vaccinated with influenza A/Singapore/INFIMH-16-0019/2016(H3N2)-like virus. Influenza A (H3N2) seroprotection (SP), seroconversion (SC), geometric mean titers (GMT), factor increase in GMT (FI-GMT) titers were assessed before and 4 weeks post-vaccination. Disease activity, therapies and adverse events (AE) were also evaluated. RESULTS: JSLE patients and controls were comparable in current age [14.5 (10.1-18.3) vs. 14 (9-18.4) years, p = 0.448] and female sex [21 (87.5%) vs. 19 (65.5%), p = 0.108]. Before vaccination, JSLE and HC had comparable SP rates [22 (91.7%) vs. 25 (86.2%), p = 0.678] and GMT titers [102.3 (95% CI 75.0-139.4) vs. 109.6 (95% CI 68.2-176.2), p = 0.231]. At D30, JSLE and HC had similar immune response, since no differences were observed in SP [24 (100%) vs. 28 (96.6%), p = 1.000)], SC [4 (16.7%) vs. 9 (31.0%), p = 0.338), GMT [162.3 (132.9-198.3) vs. 208.1 (150.5-287.8), p = 0.143] and factor increase in GMT [1.6 (1.2-2.1) vs. 1.9 (1.4-2.5), p = 0.574]. SLEDAI-2K scores [2 (0-17) vs. 2 (0-17), p = 0.765] and therapies remained stable throughout the study. Further analysis of possible factors influencing vaccine immune response among JSLE patients demonstrated similar GMT between patients with SLEDAI < 4 compared to SLEDAI ≥ 4 (p = 0.713), as well as between patients with and without current use of prednisone (p = 0.420), azathioprine (p = 1.0), mycophenolate mofetil (p = 0.185), and methotrexate (p = 0.095). No serious AE were reported in both groups and most of them were asymptomatic (58.3% vs. 44.8%, p = 0.958). Local and systemic AE were alike in both groups (p > 0.05). CONCLUSION: This is the first study that identified adequate immune protection against H3N2-influenza strain with additional vaccine-induced increment of immune response and an adequate safety profile in JSLE. ( www. CLINICALTRIALS: gov , NCT03540823).

Sequence-Based Antigenic Analyses of H1 Swine Influenza A Viruses from Colombia (2008-2021) Reveals Temporal and Geographical Antigenic Variations.

Swine influenza is a respiratory disease that affects the pork industry and is a public health threat. It is caused by type A influenza virus (FLUAV), which continuously undergoes genetic and antigenic variations. A large amount of information regarding FLUAV in pigs is available worldwide, but it is limited in Latin America. The HA sequences of H1 subtype FLUAV-positive samples obtained from pigs in Colombia between 2008-2021 were analyzed using sequence-based antigenic cartography and N-Glycosylation analyses. Of the 12 predicted global antigenic groups, Colombia contained five: four corresponding to pandemic strains and one to the classical swine H1N1 clade. Circulation of these clusters was observed in some regions during specific years. Ca2 was the immunodominant epitope among Colombian viruses. The counts of N-Glycosylation motifs were associated with the antigenic cluster ranging from three to five. The results show for the first time the existence of antigenic diversity of FLUAV in Colombia and highlight the impact of spatial and temporal factors on this diversity. This study provides information about FLUAV variability in pigs under natural conditions in the absence of vaccination and emphasizes the need for surveillance of its phylogenetic and antigenic characteristics.

Immunological profile of mice immunized with a polyvalent virosome-based influenza vaccine.

BACKGROUND: Influenza A virus (IAV) causes respiratory disease in pigs and is a major concern for public health. Vaccination of pigs is the most successful measure to mitigate the impact of the disease in the herds. Influenza-based virosome is an effective immunomodulating carrier that replicates the natural antigen presentation pathway and has tolerability profile due to their purity and biocompatibility. METHODS: This study aimed to develop a polyvalent virosome influenza vaccine containing the hemagglutinin and neuraminidase proteins derived from the swine IAVs (swIAVs) H1N1, H1N2 and H3N2 subtypes, and to investigate its effectiveness in mice as a potential vaccine for swine. Mice were immunized with two vaccine doses (1 and 15 days), intramuscularly and intranasally. At 21 days and eight months later after the second vaccine dose, mice were euthanized. The humoral and cellular immune responses in mice vaccinated intranasally or intramuscularly with a polyvalent influenza virosomal vaccine were investigated. RESULTS: Only intramuscular vaccination induced high hemagglutination inhibition (HI) titers. Seroconversion and seroprotection (> 4-fold rise in HI antibody titers, reaching a titer of ≥ 1:40) were achieved in 80% of mice (intramuscularly vaccinated group) at 21 days after booster immunization. Virus-neutralizing antibody titers against IAV were detected at 8 months after vaccination, indicating long-lasting immunity. Overall, mice immunized with the virosome displayed greater ability for B, effector-T and memory-T cells from the spleen to respond to H1N1, H1N2 and H3N2 antigens. CONCLUSIONS: All findings showed an efficient immune response against IAVs in mice vaccinated with a polyvalent virosome-based influenza vaccine.