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Human influenza A and B viruses are highly contagious and cause similar illnesses and seasonal epidemics. Currently available antiviral drugs have limited efficacy in humans with compromised immune systems; therefore, alternative strategies for protection are needed. Here, we investigated whether monoclonal antibodies (MAbs) targeting hemagglutinin (HA) and/or neuraminidase (NA) proteins would protect immunosuppressed mice from severe infections with influenza B virus. Pharmacologically immunosuppressed BALB/c mice were inoculated with B/Brisbane/60/2008 (BR/08) influenza virus and were treated with a single dose of 1, 5, or 25 mg/kg of body weight per day of either an anti-HA MAb (1D2) or an anti-NA MAb (1F2) starting at 24 hours postinoculation (hpi). Monotherapy with 1D2 or 1F2 MAbs provided dose-dependent protection of mice, with decreased BR/08 virus replication and spread in the mouse lungs, compared with those of controls. Combination treatment with 1D2 and 1F2 provided greater protection than did monotherapy, even when started at 48 hpi. Virus spread was also efficiently restrained within the lungs, being limited to 6%, 10%, and 10% of that seen in active infection when treatment was initiated at 24, 48, and 72 hpi, respectively. In most cases, the expression of cytokines and chemokines was altered according to when treatment was initiated. Higher expression of proinflammatory IP-10 and MCP-1 in combination-treatment groups, but not in monotherapy groups, to some extent, promoted better control of virus spread within the lungs. This study demonstrates the potential value of MAb immunotherapy in treating influenza in immunocompromised hosts who are at increased risk of severe disease., (Copyright © 2020 American Society for Microbiology.)

Background & Objectives: Influenza virological surveillance is an essential tool for the early detection of novel genetic variants of epidemiologic and clinical significance. This study was aimed to genetically characterize A(H1N1)pdm09 virus circulating in 2017 and to compare it with the global data., Methods: The regional/State Viral Research and Diagnostic Laboratories (VRDLs) provided influenza diagnosis for referred clinical samples and shared influenza A(H1N1)pdm09 positives with the Indian Council of Medical Research-National Institute of Virology (ICMR-NIV), Pune, India, for hemagglutinin (HA) gene phylogenetic analysis. Sites at Manipal, Jaipur and Dibrugarh performed the sequencing and shared the sequence data for analysis. The antiviral susceptibility of influenza viruses was assessed for known molecular marker H275Y at the ICMR-NIV, Pune., Results: All the eight VRDLs had well-established influenza diagnostic facilities and showed increased activity of influenza A(H1N1)pdm09 during 2017. Phylogenetic analysis showed that the viruses from the different regions of the country were similar to A/Michigan/45/2015 strain which was the 2017-2018 recommended vaccine strain and were clustered with the globally circulating clade 6B.1 with signature mutations S84N, S162N and I216T. The clade 6B.1 showed further subgrouping with additional mutations S74R, S164T and I295V; however, there was no significant association between the presence of these mutations and severity of disease due to influenza. All the study viruses were sensitive to oseltamivir., Interpretation & Conclusions: During the study period, all the study sites reported globally circulating A/Michigan/45/2015 vaccine strain of influenza A(H1N1)pdm09 viruses and remained sensitive to oseltamivir. Further genetic and antigenic characterization of influenza viruses is recommended to address public health concerns., Competing Interests: None

Influenza viruses are major respiratory pathogens that cause seasonal epidemics and occasional pandemics. Immune response to influenza viruses is majorly targeted against the hemagglutinin antigen. A laboratory-based retrospective cross-sectional study was conducted on 50 acute and 50 follow-up samples to assess the immune response to influenza A(H1N1)pdm09 virus after natural infection and detect the presence of pre-existing antibodies against influenza A(H3N2) and influenza B viruses. Two-fourfold rise in hemagglutination-inhibition (HAI) titer was observed in 100% of the follow-up samples for influenza A(H1N1)pdm09 virus. No change in HAI titers for influenza A(H3N2) and influenza B viruses was observed.

The development of a broadly protective or universal influenza virus vaccine is currently a public health priority worldwide. The vast majority of these efforts is exclusively focused on influenza A viruses. While influenza A viruses cause the majority of all influenza cases worldwide, influenza B viruses should not be ignored. Approximately 25% of all influenza cases are caused by influenza B viruses which circulate as two distinct B/Victoria/2/87-like and B/Yamagata/16/88-like lineages. In contrast to popular belief, influenza B cases frequently cause significant morbidity and mortality, especially in children. Similar to influenza A viruses, influenza B viruses drift antigenically and the influenza B components of current vaccines have to be reformulated almost on an annual basis. A broadly protective vaccine against influenza B viruses is therefore urgently needed. Here we review both broadly protective anti-influenza B antibodies as well as the sparse attempts to create a universal influenza B virus vaccine., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Molecular characterization of neuraminidase (NA) gene of 25 influenza A(H3N2) virus isolates (2009-2013) archived at the Manipal Centre for Virus Research was carried out. The annual rate of amino acid substitutions in the N2 gene of influenza A(H3N2) virus isolates was 0.2-0.6%. Out of the 25 NA sequences analyzed, catalytic site mutations were observed in three isolates. Two of the mutations (D151G and E276G) were detected in functional catalytic residues, and an E227V mutation was detected in the framework residues. To the best of our knowledge, NA inhibitor resistance associated with the mutations E276G and E227V has not been reported. However, the mutation D151G, which is commonly associated with culturing of influenza A(H3N2) virus in Madin-Darby canine kidney (MDCK) cells, has been reported to result in a reduction in virus susceptibility to NA inhibitor drugs. Our study also detected mutations in antigenic residues. Some of the mutations (except D197G, K249E, A250T, S334C, and H347R/N) remained conserved in isolates of succeeding seasons. Antigenic residue mutations (D197G and S334C) have not been reported globally to date. The effect of these catalytic and antigenic mutant residues on drug and antibody binding was analyzed using three-dimensional structural analysis and biochemical assays. Antigenic variability of influenza A(H3N2) viruses is a major concern, and vaccine failures are mainly due to genetic variations in the HA gene. Our study documents that genetic changes in N2 occur at a slower rate, and this information is useful for the consideration and standardization of NA in influenza vaccines.

Genetic analysis of neuraminidase gene sequences in 23 archived isolates of influenza A(H1N1)pdm09 virus, isolated during the 2009-2012 influenza seasons, was carried out to determine the genetic variability. Amino acid substitutions were observed at the rates of 0.3-0.7% per year. The catalytic site consisting of 8 functional and 11 framework residues were found conserved in 20 isolates and mutated in three (E228G, E278G, and N295T) isolates. To the best of our knowledge the three catalytic site mutants observed in our study have not been reported elsewhere to date. Similarly, mutations in the antigenic sites (K217E, K254E, V267A, and D451E except I263V) are discussed for the first time through this article. The effect of these mutations on drug and antibody binding were analyzed using biochemical and structural studies. Detailed studies on the neuraminidase gene are sparse and our study may serve as an appropriate platform to gain insights about the evolution of influenza virus, thereby facilitating drugs/vaccines design and development. J. Med. Virol. 89:202-212, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Influenza, the most common infectious disease, poses a great threat to human health because of its highly contagious nature and fast transmissibility, often leading to high morbidity and mortality. Effective vaccination strategies may aid in the prevention and control of recurring epidemics and pandemics associated with this infectious disease. However, antigenic shifts and drifts are major concerns with influenza virus, requiring effective global monitoring and updating of vaccines. Current vaccines are standardized primarily based on the amount of hemagglutinin, a major surface antigen, which chiefly constitutes these preparations along with the varying amounts of neuraminidase (NA). Anti-influenza drugs targeting the active site of NA have been in use for more than a decade now. However, NA has not been approved as an effective antigenic component of the influenza vaccine because of standardization issues. Although some studies have suggested that NA antibodies are able to reduce the severity of the disease and induce a long-term and cross-protective immunity, a few major scientific issues need to be addressed prior to launching NA-based vaccines. Interestingly, an increasing number of studies have shown NA to be a promising target for future influenza vaccines. This review is an attempt to consolidate studies that reflect the strength of NA as a suitable vaccine target. The studies discussed in this article highlight NA as a potential influenza vaccine candidate and support taking the process of developing NA vaccines to the next stage.