Neuraminidase Type Research Articles

Machine Learning Using Template-Based-Predicted Structure of Haemagglutinin Predicts Pathogenicity of Avian Influenza.

Deep learning presents a promising approach to complex biological classifications, contingent upon the availability of well-curated datasets. This study addresses the challenge of analyzing three-dimensional protein structures by introducing a novel pipeline that utilizes open-source tools to convert protein structures into a format amenable to computational analysis. Applying a two-dimensional convolutional neural network (CNN) to a dataset of 12,143 avian influenza virus genomes from 64 countries, encompassing 119 hemagglutinin (HA) and neuraminidase (NA) types, we achieved significant classification accuracy. The pathogenicity was determined based on the presence of H5 or H7 subtypes, and our models, ranging from zero to six mid-layers, indicated that a four-layer model most effectively identified highly pathogenic strains, with accuracies over 0.9. To enhance our approach, we incorporated Principal Component Analysis (PCA) for dimensionality reduction and one-class SVM for abnormality detection, improving model robustness through bootstrapping. Furthermore, the K-nearest neighbor (K-NN) algorithm was fine-tuned via hyperparameter optimization to corroborate the findings. The PCA identified distinct clustering for pathogenic HA, yielding an AUC of up to 0.85. The optimized K-NN model demonstrated an impressive accuracy between 0.96 and 0.97. These combined methodologies underscore our deep learning framework's capacity for rapid and precise identification of pathogenic avian influenza strains, thus providing a critical tool for managing global avian influenza threats.

Clinical profile and outcome of H1N1 influenza patients in a tertiary care hospital in Kochi, Kerala

Background: After the 2009 pandemic, a re-emergence of hemagglutinin type 1 and neuraminidase type 1 (H1N1) influenza cases has been noted in India recently. The number of swab-positive cases has increased in the year 2017 compared to yesteryears. Since the current circulating strain (A/Michigan/7/2009 [H1N1] pdm09) is different from previous pandemic strains, a look into the clinical profile is imperative. Aims: The aim is to study the clinical, biochemical, and radiological profile of H1N1 patients at initial presentation and its influence on the mode of treatment and outcome. Patients and Methods: A cross-sectional record-based analysis of all confirmed cases of H1N1 influenza admitted at Lourdes Hospital, Kochi, Kerala, between 2015 and 2017. Confirmation of cases was done by reverse transcriptase polymerase chain reaction of respiratory specimens at Manipal Centre for Virus Research. Results: A total of 76 confirmed cases of H1N1 influenza were detected during the study period of which 36 required Intensive Care Unit admission. Most patients were between 51 and 60 years (25%). The predominant presenting symptoms were fever (98.7%), dry cough (61.8%), breathlessness (53.9%), and the most common auscultatory finding being bilateral crepitations (64.47%). Around 32.89% of cases presented with bilateral lung infiltrates on X-ray. Sixty-nine of 76 patients (90.79%) survived the disease. Conclusions: Vaccination, early recognition of the disease, and prompt initiation of treatment seem to be the only way to reduce H1N1 disease progression and associated mortality. Patients with risk factors require additional attention as clinical course can be unpredictable. Pregnancy is associated with higher rate of complications. Early respiratory support helped in preventing progression to respiratory failure in most of our patients.

Convalescent Plasma Therapy: A Treatment of Choice for COVID-19 during Current Pandemic

The severe acute respiratory syndrome coronavirus 2 which is the source of pandemic coronavirus disease 2019 has engulfed almost whole world. This virus was first reported in Wuhan city (China) in December 2019. Since the discovery of the virus, till today the researchers and scientists have been working to develop new vaccines or therapeutic agents against severe acute respiratory syndrome coronavirus 2. However, thus far no vaccine has emerged that can be approved to treat or prevent coronavirus disease 2019. Due to lack of specific preventative and therapeutic options for the treatment of coronavirus disease 2019, the use of convalescent plasma therapy may be of great benefit in the current situation. Previous use of immune plasma has resulted in successful treatment of hemagglutinin type 1 and neuraminidase type 1 influenza virus, Middle East respiratory syndrome coronavirus and severe acute respiratory syndrome coronavirus 1 epidemics. In the current scenario raised by coronavirus disease 2019, the convalescent plasma therapy has been applied successfully among many patients across various regions. This article presents an up-to-date review of existing literature on recovery through convalescent plasma as a treatment of choice, safety and its efficacy, possibility and its challenges for the treatment of coronavirus disease 2019.

Bivalent vaccination with NA1 and NA2 neuraminidase virus-like particles is protective against challenge with H1N1 and H3N2 influenza A viruses in a murine model

Neuraminidase (NA) is the second most abundant glycoprotein on the surface of influenza A viruses (IAV). Neuraminidase type 1 (NA1) based virus-like particles (VLPs) have previously been shown to protect against challenge with H1N1 and H3N2 IAV. In this study, we produced neuraminidase type 2 (NA2) VLPs derived from the sequence of the seasonal IAV A/Perth/16/2009. Intramuscular vaccination of mice with NA2 VLPs induced high anti-NA serum IgG levels capable of inhibiting NA activity. NA2 VLP vaccination protected against mortality in a lethal A/Hong Kong/1/1968 (H3N2) virus challenge model, but not against lethal challenge with A/California/04/2009 (H1N1) virus. However, bivalent vaccination with NA1 and NA2 VLPs demonstrated no antigenic competition in anti-NA IgG responses and protected against lethal challenge with H1N1 and H3N2 viruses. Here we demonstrate that vaccination with NA VLPs is protective against influenza challenge and supports focusing on anti-NA responses in the development of future vaccination strategies.

Human Leukocyte Antigen-DR Deficiency and Immunosuppression-Related End-Organ Failure in SARS-CoV2 Infection.

Human Leukocyte Antigen-DR Deficiency and Immunosuppression-Related End-Organ Failure in SARS-CoV2 Infection.

Echoes of 2009 H1N1 Influenza Pandemic in the COVID Pandemic

The severe acute respiratory syndrome–related coronavirus-2 (SARS-CoV2) pandemic that has engulfed the globe has had incredible effects on health care systems and economic activity. Social distancing and school closures have played a central role in public health efforts to counter the coronavirus disease 2019 (COVID)-19 pandemic. The most recent global pandemic prior to COVID-19 was the 2009 pandemic, hemagglutinin type 1 and neuraminidase type 1 (H1N1) influenza. The course of events in 2009 offer some rich lessons that could be applied to the current COVID-19 pandemic. This commentary highlights some of the most relevant points and a discussion of possible outcomes of the COVID-19 pandemic.

Neuraminidase 1 and 2 Active Site Comparison for Viral Drug Resistance Analysis

Neuraminidase is an important protein on the surface of influenza and is an antiviral target. There are several types of neuraminidase, but this project focuses on neuraminidase 1 (N1) and 2 (N2) because of their prevalence in human influenza A infections. The amino acid residues in the active sites of N1 and N2 are 94% identical. However, there are several key differences that affect how N1 and N2 interact with the same antiviral drug. The purpose of this project is to gain a deeper understanding of viral drug resistance by modeling the active sites of N1 and N2 and their interactions with oseltamivir (Tamiflu). Two PDB files have been selected for N1 (2HU4) and N2 (4GZP). These PDB files will initially be overlaid in Jmol to identify the level of structural similarity, then active site boxes will be 3D printed for N1 and N2. Active site boxes model only the active site of a molecule, giving a detailed view and understanding of this specific location. Within the models for N1 and N2, Jmol will be used to highlight amino acids E276, I222, and H274Y to investigate their effects on inhibitor interactions. Additionally, a model of the inhibitor oseltamivir (Tamiflu) will be 3D printed to compare its interactions with N1 and N2. These active site boxes will enhance the scientific education and study of these active sites.Support or Funding InformationThis work is part of the CREST program, supported by National Science Foundation Grants I022793, I323414, and 172s940.

Passaging of an influenza A(H1N1)pdm09 virus in a difluoro sialic acid inhibitor selects for a novel, but unfit I106M neuraminidase mutant

An influenza A(H1N1)pdm09 and an influenza B virus were passaged in 3-fluoro(eq)-4-guanidino difluoro sialic acid (3Feq4Gu DFSA), an inhibitor of the influenza neuraminidase (NA) to determine whether resistant variants could be selected. 3Feq4Gu DFSA is a mechanism-based inhibitor, forming a covalent link to Y406 in the NA active site. Given its similarity to the natural substrate, sialic acid, we predicted resistant variants would be difficult to select. Yields of both viruses decreased with passaging, so that after 12 passages both viruses were only growing to low titers. Drug concentrations were decreased for another three passages. There was no difference in NA sensitivity in the MUNANA fluorescence-based assay, nor in plaque assays for the passaged virus stocks. All influenza B plaques were still wild type in all assays. There were isolated small diffuse plaques in the P15 pdm09 stock, which after purification had barely detectable NA or hemagglutinin (HA) activity. These had a novel non-active site I106M substitution in the NA gene, but unexpectedly no HA changes. The I106M may impact NA function through steric effects on the movement of the 150 and 430-loops. The I106M viruses had similar replication kinetics in MDCK cells as wild type viruses, but their ability to bind to and infect CHO–K1 cells expressing high levels of cell-bound mucin was compromised. The I106M substitution was unstable, with progeny rapidly reverting to wild type by three different mechanisms. Some had reverted to I106, some had V106, both with wild type NA and HA properties. A third group retained the I106M, but had a compensating R363K substitution, which regained almost wild type NA properties. These viruses now agglutinated chicken red blood cells (CRBCs) but unlike the I/V106, they rebound after elution at 37 °C. There were no mutations in the HA, but each phenotype correlated with the NA sequence. We propose that the activity in the I106M mutant is insufficient to remove carbohydrates from the virion HA and NA, sterically limiting HA access to CRBC receptors, thus resulting in poor HA binding.

Impact of tetramerization on the ligand recognition of N1 influenza neuraminidase via MMGBSA approach.

Influenza virus neuraminidase (NA) is a homotetrameric surface protein that, in contrast to other non-influenza NAs, requires a quaternary assembly to exhibit enzymatic activity, suggesting that the oligomeric state significantly impacts the active site of influenza NA. Nevertheless, most structure-based drug design studies have been reported by employing the monomeric state in the closed or open-loop due to the computational cost of employing the tetrameric NA. In this work, we present MD simulations coupled to the MMGBSA approach of avian N1 type NA in its monomeric and tetrameric closed and open-loop state both with and without the inhibitor oseltamivir and its natural substrate, sialic acid. Structural and energetic analyses revealed that the tetrameric state impacts flexibility as well as the map of interactions participating in stabilizing the protein-ligand complexes with respect to the monomeric state. It was observed that the tetrameric state exerts dissimilar effects in binding affinity, characteristic of positive and negative cooperativity for oseltamivir and sialic acid, respectively. Based on our results, to perform a confident structure-based drug design, as well as to evaluate the impact of key mutations through MD simulations, it is important to consider the tetrameric state closed-loop state.

In silico prediction of drug resistance due to S247R mutation of Influenza H1N1 neuraminidase protein

We present here in silico studies on antiviral drug resistance due to a novel mutation of influenza A/H1N1 neuraminidase (NA) protein. Influenza A/H1N1 virus was responsible for a recent pandemic and is currently circulating among the seasonal influenza strains. M2 and NA are the two major viral proteins related to pathogenesis in humans and have been targeted for drug designing. Among them, NA is preferred because the ligand-binding site of NA is highly conserved between different strains of influenza virus. Different mutations of the NA active site residues leading to drug resistance or susceptibility of the virus were studied earlier. We report here a novel mutation (S247R) in the NA protein that was sequenced earlier from the nasopharyngeal swab from Sri Lanka and Thailand in the year 2009 and 2011, respectively. Another mutation (S247N) was already known to confer resistance to oseltamivir. We did a comparative study of these two mutations vis-a-vis the drug-sensitive wild type NA to understand the mechanism of drug resistance of S247N and to predict the probability of the novel S247R mutation to become resistant to the currently available drugs, oseltamivir and zanamivir. We performed molecular docking- and molecular dynamics-based analysis of both the mutant proteins and showed that mutation of S247R affects drug binding to the protein by positional displacement due to altered active site cavity architecture, which in turn reduces the affinity of the drug molecules to the NA active site. Our analysis shows that S247R may have high probability of being resistant.

Retrospective analysis of maternal and foetal outcome of H1N1 influenza amongst antenatal mothers at a tertiary care hospital

Background: Pregnancy is an immunocompromised state where in infections are common. H1N1 (hemagglutinin type 1 and neuraminidase type 1) Influenza is a seasonal epidemic, considered as an alarming infection across the world with high rates of maternal mortality each year. The principal intention of this study was to elicit the clinical profile of antenatal mothers with H1N1 and subsequently to analyse the risk factors, prognosis and the materno-fetal outcome. Extensive review of literature with current guidelines and management protocols has been highlighted. Methodology: This is a retrospective observational study performed in Sri Ramachandra University and Research Institute over the period of one year from January 2016 – March 2017, the clinical course of the patients who were confirmed with H1N1 influenza using throat swab RT-PCR assay was analysed. Statistical analysis was done by SPSS, version 11. Results: A total of 62 antenatal patients with symptoms suggestive of H1N1 influenza were tested for H1N1 out of which 12 were positive, which accounted for 19.35% positivity. The mean age was 24 years with a range of 22-30 years. The epidemic peaked in the month of November to January. Fever with cough was the most common clinical manifestation. Most of the patients were hospitalized and treated with oseltamivir. All the positive patients, were advised home isolation for 5-7 days after discharge. This indexed study had an overall mortality rate of 8.3%. Acute respiratory distress syndrome and multiple organ dysfunction were the most common cause of death. Conclusion: Most of the patients recuperated well with close vigilance, symptomatic and antiviral treatment, went on to deliver healthy baby. Proper prevention steps, personal hygiene and admission to designated swine flu ward can be helpful in preventing the spread in the community. Respiratory failure and sepsis were the cause of mortality among the patients of this study.

Synthesis of Pyrazine-1,3-thiazine Hybrid Analogues as Antiviral Agent Against HIV-1, Influenza A (H1N1), Enterovirus 71 (EV71), and Coxsackievirus B3 (CVB3).

A novel series of pyrazine-1,3-thiazine hybrid conjugates were synthesized in excellent yield. These derivatives were subsequently tested against human immunodeficiency virus (HIV-1); hemagglutinin type 1 and neuraminidase type 1-'influenza' A (H1N1) virus; enterovirus 71 (EV71); and coxsackievirus B3. The effect of these conjugates on the key enzymes responsible for the progression of these viral infections was also illustrated via enzyme-based assay, such as HIV-1 reverse transcriptase (RT) and neuraminidase, where entire tested molecules showed considerable inhibition. Particularly, among the tested derivatives, compound 3k was identified as most promising inhibitor of HIV-1 with 94% of inhibition (IC50 3.26 ± 0.2 μm). Moreover, the compound 3d was found to be the most potent analogue to inhibit the H1N1 virus with IC50 of 5.32 ± 0.4 μm together with inhibition of the neuraminidase enzyme (IC50 11.24 ± 1.1 μm). In regard to inhibitory activity against enterovirus 71 (EV71) and coxsackievirus B3 (CVB3), the tested derivatives showed considerable inhibition of infection. Molecular docking studies were also performed for the most promising inhibitors with their corresponding target protein to exemplify the structural requirement for better inhibitory activity. The results of inhibitory assay showed that designed molecules possess considerable inhibitory activity against the virus tested.

Role of Corticosteroids in Influenza Pneumonia (H1N1) Patients

Background and objective: Although the benefits of systemic corticosteroids in pneumonia are not clear, their use is frequent in clinical practice. We described the patients' characteristics, demographics and the effect of steroids in Influenza pneumonia Hemagglutinin Type 1 and Neuraminidase Type 1 (H1N1) patients in terms of length of hospital stay. METHODS: The study design was a retrospective observational study, which consisted of patients presenting with H1N1 infection to the department of Emergency medicine at tertiary referral centre. We investigated all cases admitted with diagnosis of H1N1 pneumonia, confirmed by collecting throat swabs and doing Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) for H1N1 infection during July 2009 to February 2011. RESULTS: Of the 115 patients, 30 patients have been administered steroids. Within those 30 patients 20 have stayed in ICU with mean 7.45 ± 5.7 days. In that group of 20 patients, 10 patients have stayed in ICU alone, 10 patients have stayed in ICU and ward with mean 10.3±6.5 and 13.6±7.4 days respectively. 10 patients have stayed only in ward with mean days of 4.8±1.9. The overall mean hospital stay is 9.8±6.6 days. It is found that there is a significant statistical relationship between corticosteroid administration and reduced hospital stay (P=0.000).

Inulin-Type β2-1 Fructans have Some Effect on the Antibody Response to Seasonal Influenza Vaccination in Healthy Middle-Aged Humans.

β2-1 fructans are prebiotics and, as such, may modulate some aspects of immune function. Improved immune function could enhance the host’s ability to respond to infections. There is limited information on the effects of β2-1 fructans on immune responses in humans. The objective of the study was to determine the effect of a specific combination of long-chain inulin and oligofructose (Orafti® Synergy1) on immune function in middle-aged humans, with the primary outcome being response to seasonal influenza vaccination. Healthy middle-aged humans (45–63 years of age) were randomly allocated to consume β2-1 fructans in the form of Orafti® Synergy1 (8 g/day; n = 22) or maltodextrin as control (8 g/day; n = 21) for 8 weeks. After 4 weeks, participants received the 2008/2009 seasonal influenza vaccine. Blood and saliva samples were collected prior to vaccination and 2 and 4 weeks after vaccination. They were used to measure various immune parameters. The primary outcome was the serum concentration of anti-vaccine antibodies. Serum antibody titers against the vaccine and vaccine-specific immunoglobulin concentrations increased post-vaccination. Antibodies to the H3N2-like hemagglutinin type 3, neuraminidase type 2-like strain were higher in the Synergy1 group (P = 0.020 for overall effect of treatment group), as was serum vaccine-specific IgG1 2 weeks post-vaccination (P = 0.028 versus control). There were no other differences between groups in antibody titers or anti-vaccine immunoglobulin concentrations, in blood immune cell phenotypes, or in a range of immune parameters. It is concluded that Orafti® Synergy1, a combination of β2-1 fructans, can enhance some aspects of the immune response in healthy middle-aged adults, but that this is not a global effect.

Clinical profile and outcome of recent outbreak of influenza A H1N1 (swine flu) at a tertiary care center in Hyderabad, Telangana

Background: Swine influenza, also called swine flu, hog flu, and pig flu, is an infection caused by any one of the several types of swine influenza viruses. The World Health organization ( WHO) raised a worldwide pandemic alert for swine flu on June 11, 2009 that was a first of its kind in the past 70 years. In India, the index cases were reported from Pune, Maharashtra. We witnessed a recent outbreak in India during late 2014 and early 2015. Methodology: A retrospective study was carried out to describe the clinical profile and outcome of the confirmed cases of swine flu who were admitted at our center between December 10, 2014 and May 11, 2015. The cases were confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) on respiratory specimens. Results: A total of 514 patients with symptoms suggestive of swine flu were tested for hemagglutinin type 1 and neuraminidase type 1 (H1N1) out of whom 88 were positive, which accounted for 17.12% positivity. The mean age was 31.15 years with a range of 11-90 years, with equal distribution among males and females (males: 45, females: 43). The epidemic peaked in the month of January (n = 44.50%). Fever (95.45%) was the most common clinical manifestation followed by cough (85.22%), breathlessness (51.22%), and myalgia (50%). The majority were in category C (59.09%) based on the severity of the illness. All the patients were hospitalized and treated with oseltamivir. Of all the positive patients, 39 (44.31%) were advised home isolation after discharge for 5-7 days in view of the mild disease. Hypertension, diabetes, existing lung diseases, cardiovascular diseases, smoking habit, alcohol consumption, and pregnancy were found to be the major risk factors. Women in the third trimester of their pregnancy were found to be at a higher risk. Our study had an overall mortality of 14.77% (n = 13). Mortality was higher among pregnant women (n = 1/6, 16.66%) compared to nonpregnant women (n = 5/37, 13.51%). Multiple organ dysfunction syndrome (MODS) and acute respiratory distress syndrome (ARDS) were the most common causes of death. Conclusion: Swine flu activity has come down significantly, with a single case being reported in the month of April and none in May in 2015 at our center.

Update on Influenza A H1N1 pdm09 virus (swine flu)

Influenza virus is a common human pathogen that causes serious respiratory illness and deaths. Influenza A viruses are further subtyped into 16 haemagglutinin (HA) types and 9 neuraminidase (NA) types. Influenza A viruses infect a variety of animals including humans, pigs, horses, sea mammals and birds. Due to the presence of segmented genome, Influenza A virus can undergo genetic reassortment in animals simultaneously infected by more than one subtypes of the virus, leading to evolution of new strains to which human beings are immunologically naive. In April 2009, a new strain of Influenza virus A H1N1, commonly referred to as “swine flu,” began to spread in several countries around the world, and caused about 2,84,000 deaths globally. The pandemic strain Influenza A/H1N1/pdm09 affected people who had no contact with pigs indicating person to person transmission, and was not detected in nature in swine or birds. The strain can be diagnosed in the laboratory by various molecular methods like real time RT-PCR and rapid diagnostic tests. Influenza A/H1N1/pdm09 strain is resistant to adamantanes and is treated by oseltamivir or zanamivir. Killed and Live vaccines containing the current circulating types of influenza A and B viruses are available for protection against the virus.

Potential activity of some natural products compounds as Neuraminidase inhibitors based on molecular docking simulation and in vitro test

Neuraminidase (NA) plays an important role in replication and the release of a new avian influenza virion. In consequence, NA has been considered as a valid target in drug design against influenza virus. The aim of this study was to identify the new neuraminidase inhibitors using molecular docking simulation based on virtual screening from natural products compounds. The X-ray crystal structure of neuraminidase type N1 (PDB id: 3B7E) and N1 mutant (PDB id: 3NNS) using Autodock 4.2 program. Zanamivir was used as the control ligand and docked against neuraminidase type N1, further plotted between log IC50 value experiments of sialic acid derivatives compound versus log of Ki value of molecular docking. Molecular docking simulation was performed on 113 herb compounds along with zanamivir and oseltamivir as the control ligands. The result showed that the best interaction against of neuraminidase N1 and N1 mutant from herbs compound is katsumadain-A withfree energy value -7,54 kcal/mol and -7,46 kkal/mol, respectively. Katsumadain-Aformed hydrogen bond with amino acid residue Arg118 and Arg371 on neuraminidase and neuraminidase N1 mutant Katsumadain-A was also connected with Arg118 through hydrogen binding interaction. This in silico results also was proved by in vitro MUNANA assay.

Neuraminidase mutations conferring resistance to laninamivir lead to faster drug binding and dissociation

The neuraminidase (NA) inhibitors oseltamivir and zanamivir are administered twice daily for 5days for treatment of influenza. Laninamivir is a 7-methoxy derivative of zanamivir, but a single dose is effective when taken as the laninamivir octanoate prodrug. We show here in IC50 kinetics assays and a solid phase reactivation assay that compared to zanamivir laninamivir also demonstrates slow binding to but slower dissociation from multiple wild type NAs. A D197E mutation in an influenza B and an E119G in an N9 neuraminidase which confer 15- and 150-fold resistance to laninamivir result in faster binding and dissociation. Despite similar IC50s our assays demonstrate more rapid dissociation of laninamivir from clade 1 compared to 2 H5N1 NAs.

Protective effect of fluvastatin on influenza virus infection

Statins are 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors and have pleiotropic effects. It has been suggested that statins may be a potential treatment during the next influenza pandemic. In a previous study we found that a statin/caffeine combination protects BALB/c mice against Influenza A, subtypes haemagglutinin type 5 and neuraminidase type 1 (H5N1), H3N2 and H1N1 infection. The effect of statins alone on influenza virus infection, however, is not known. In this study, it was investigated whether fluvastatin is capable of inhibiting influenza A virus replication in vitro. The results demonstrated that the synthesis of viral RNA and protein was affected by fluvastatin treatment. Virus production was markedly reduced when fluvastatin was administered simultaneously with the virus; however, a greater inhibition was observed when fluvastatin was added following viral adsorption. The selectivity index [SI; 50% cytotoxic concentration (CC50)/50% inhibition concentration (IC50)], however, was only 21. It was further demonstrated that fluvastatin protects host cells against influenza-induced inflammation by reducing the production of tumour necrosis factor-α, interleukin 8 and interferon γ. In conclusion, the results demonstrated that fluvastatin exerted a minor inhibitory effect on influenza virus infection, which involved anti-inflammatory activities.

Vaccination with recombinant PIV5 expressing influenza neuraminidase provides protection against homologous and heterologous influenza virus infection (P4291)

Abstract Vaccination is considered the most effective measure for controlling influenza virus infection, however current vaccination methods are inadequate. Virus-vectored vaccines offer an appealing alternative. Parainfluenza virus 5 (PIV5), a non-segmented, negative-stranded RNA virus (NNSV) in the family Paramyxoviridae is an appealing vector candidate as it has a stable genome without a DNA phase in its life cycle, is readily grown to high titers in approved vaccine cell lines, and infects many mammals without causing disease. Neuraminidase (NA), a glycoprotein found on the surface of influenza A virus as well as virus-infected cells is more conserved than the hemagglutinin surface glycoprotein, the primary antigen in current influenza vaccines. This increases the likelihood of achieving broad protection if used as a vaccine antigen. We show that vaccination with PIV5 expressing the NA from H5N1 highly pathogenic avian influenza (HPAI; rPIV5-N1 (H5N1)) or pandemic H1N1 (rPIV5-N1 (H1N1)) primes robust NA-specific antibody and T cell responses and confers complete protection against homologous (NA-matched) influenza virus challenge. Moreover, immunization also confers significant cross-protection against challenge with heterologous influenza virus within the same NA type. These results suggest that NA can be an effective vaccine antigen and protect against even a stringent challenge, such as with H5N1 HPAI virus, making it an appealing candidate pandemic influenza vaccine.