Recent Influenza Research Articles

Antiviral Agents Derived from Novel 1-adamantyl Singlet Nitrenes

Amantadine constitutes an interesting, diamond crystal lattice-shaped, antivirally active amine with an inhibitory effect on influenza A viruses causing common 'flu' in humans. Unfortunately, amantadine forfeited most of its therapeutic potential because of resistance development in recent influenza A virus isolates. The antiviral efficacy of amantadine congeners can be chemically modified, resulting in re-constitution, improvement and/or extension of antiviral activities mediated by amino-adamantyls. Newly synthesized compounds were evaluated towards HIV type-1 (HIV-1) replication in primary human lymphocytes. One N-phenacyl amantadine derivative was investigated for inhibiting the in vitro replication of respiratory viruses (influenza A viruses, influenza B virus, human parainfluenza virus type 3 and severe acute respiratory syndrome coronavirus). Two ketone-stabilized 1-adamantyl singlet nitrenes were discovered serendipitously. To our best knowledge these are the first persistently stable nitrenes to be reported. Their structure was proved by determining the X-ray single crystal structure of one hydrolytic elaboration product. This salt adduct revealed an incommensurately modulated crystal structure, which was solved by extensive computational refinement. We could show that ketone-stabilized 1-adamantyl singlet nitrenes are versatile synthons for the synthesis of antiviral drug candidates. An amantadine-folate conjugate was inhibitory on HIV-1 replication in primary human lymphocytes, and one N-phenacyl amantadine derivative was inhibitory towards low pathogenic avian influenza A virus (H5N1) replication in vitro. These results indicate that the aromatic-aliphatic ketone-stabilized 1-adamantyl singlet nitrenes, beyond being of fundamental interest in organic chemistry, represent versatile synthons for the synthesis of new amantadine-related potentially antiviral drugs.

Genetic diversity of early (1998) and recent (2010) avian influenza H9N2 virus strains isolated from poultry in Iran

Infection with avian influenza H9N2 virus is widespread in the Asian poultry industry, resulting in great economic losses due to mortality and a severe decline in egg production. To obtain more-comprehensive genomic data from circulating H9N2 viruses in Iran, we sequenced the whole genomes of early (Ck/IR/ZMT-101/98) and recent (Ck/IR/EBGV-88/10) isolates of this virus in Iran. The M and NS genes of Ck/IR/EBGV-88/10 shared a high level of similarity with a highly pathogenic H7N3 virus isolated from Pakistan. The cleavage site within the HA protein of these viruses contained two different motifs, RSSR and KSSR, which are similar to those found in low-pathogenic viruses. The deduced amino acid sequence of the new isolate contained the mutation Q226L, which is a characteristic of human-type sialic acid influenza receptor binding. An analysis of the viral amino acid sequence of the M2 protein of the recent strain revealed a V27A mutation, which is associated with amantadine resistance in avian influenza virus. The present results emphasize the need for continuous surveillance of H9N2 viruses in poultry and the human population to obtain more information about the nature and evolution of future pandemic influenza viruses.

Participation of ICUs in Critical Care Pandemic Research

Little information exists to identify barriers to participation in pandemic research involving critically ill patients. We sought to characterize clinical research activity during the recent influenza A pandemic and to understand the experiences, beliefs, and practices of key stakeholders involved in pandemic research implementation. Cross-sectional, provincial postal questionnaire. Level III ICUs. ICU administrators and research coordinators. We used rigorous survey methodology to identify potential respondents and to develop, test, and administer two-related questionnaires. We analyzed responses from 39 research coordinators and 139 administrators (response rates: 70.9% and 73.2%, respectively). Compared with non-influenza A studies, influenza A studies were less likely to be randomized trials and most often investigator-initiated and peer-review funded. Whereas both respondent groups felt that pandemic research would be helpful in providing care during future pandemics, research coordinators placed significantly greater importance on their ICU's participation in pandemic research. Both respondent groups expressed a need for rapid approval processes, designated funding for research personnel, adequate funding for start-up and patient screening, preapproved template protocols and consent forms, and clearer guidance regarding co-enrollment. Research coordinators acknowledged a need for alternative consent models to increase their capacity to participate in future pandemic research. More administrators expressed willingness to participate in the next pandemic if the required research resources were made available to them. Whereas research personnel and administrators support participation in pandemic ICU research, several modifiable barriers to participation exist. Pandemic research preparedness planning with regulatory bodies and dedicated funding to support research infrastructure, especially in community settings, are required to optimize future pandemic research participation.

Structural and Functional Characterization of K339T Substitution Identified in the PB2 Subunit Cap-binding Pocket of Influenza A Virus

Influenza virus RNA-dependent RNA polymerase is a heterotrimer composed of PA, PB1, and PB2 subunits. RNA-dependent RNA polymerase is required for both transcription and replication of influenza viral RNA taking place in the nucleus of infected cells. A "cap-snatching" mechanism is used to generate a 5'-capped primer for transcription in which the cap-binding domain of PB2 (PB2cap) captures the 5' cap of the host pre-mRNA. Our statistical analysis of PB2 sequences showed that residue Lys(339) located in the cap-binding pocket of H5N1 PB2cap was gradually replaced by Thr(339) over the past decade. To understand the role of this amino acid polymorphism, we solved the crystal structures of PB2cap with or without a pre-mRNA cap analog, m(7)GTP, in the presence of Lys(339) or Thr(339). The structures showed that Lys(339) contributes to binding the γ-phosphate group of m(7)GTP, and the replacement of Lys(339) by Thr eliminates this interaction. Isothermal titration calorimetry analysis showed that Thr(339) attenuated the PB2cap cap binding activity in vitro compared with Lys(339). Further functional studies confirmed that Thr(339)-PB2-containing ribonucleoprotein complex has a reduced influenza polymerase activity and RNA synthesis activity, and a reconstituted H5N1 virus containing the Thr(339) substitution exhibited a lower virulence to mice but more active replication in Madin-Darby canine kidney cells. The K339T substitution in the cap-binding pocket of PB2 modulates the polymerase activity and virulence by regulating the cap binding activity. It is informative to track variations in the cap-binding pocket of PB2 in surveillance of the evolution and spread of influenza virus.

Prior infection of pigs with a recent humanH3N2 influenza virus confers minimal cross‐protection against aEuropean swineH3N2 virus

H3N2 influenza viruses circulating in humans and European pigs originate from the pandemic A/Hong Kong/68 virus. Because of slower antigenic drift in swine, the antigenic divergence between swine and human viruses has been increasing. It remains unknown to what extent this results in a reduced cross-protection between recent human and swine H3N2 influenza viruses. We examined whether prior infection of pigs with an old [A/Victoria/3/75 (A/Vic/75)] or a more recent [A/Wisconsin/67/05 (A/Wis/05)] human H3N2 virus protected against a European swine H3N2 virus [sw/Gent/172/08 (sw/Gent/08)]. Genetic and antigenic relationships between sw/Gent/08 and a selection of human H3N2 viruses were also assessed. After challenge with sw/Gent/08, all challenge controls had high virus titers in the entire respiratory tract at 3days post-challenge and nasal virus excretion for 5-6days. Prior infection with sw/Gent/08 or A/Vic/75 offered complete virological protection against challenge. Pigs previously inoculated with A/Wis/05 showed similar virus titers in the respiratory tract as challenge controls, but the mean duration of nasal shedding was 1·3days shorter. Unlike sw/Gent/08- and A/Vic/75-inoculated pigs, A/Wis/05-inoculated pigs lacked cross-reactive neutralizing antibodies against sw/Gent/08 before challenge, but they showed a more rapid antibody response to sw/Gent/08 than challenge controls after challenge. Cross-protection and serological responses correlated with genetic and antigenic differences. Infection immunity to a recent human H3N2 virus confers minimal cross-protection against a European swine H3N2 virus. We discuss our findings with regard to the recent zoonotic infections of humans in the United States with a swine-origin H3N2 variant virus.

Influenza and Pneumococcal Immunization

Influenza and Pneumococcal Immunization

The Effect of Age and Recent Influenza Vaccination History on the Immunogenicity and Efficacy of 2009–10 Seasonal Trivalent Inactivated Influenza Vaccination in Children

BackgroundThere is some evidence that annual vaccination of trivalent inactivated influenza vaccine (TIV) may lead to reduced vaccine immunogenicity but evidence is lacking on whether vaccine efficacy is affected by prior vaccination history. The efficacy of one dose of TIV in children 6–8 y of age against influenza B is uncertain. We examined whether immunogenicity and efficacy of influenza vaccination in school-age children varied by age and past vaccination history.Methods and FindingsWe conducted a randomized controlled trial of 2009–10 TIV. Influenza vaccination history in the two preceding years was recorded. Immunogenicity was assessed by comparison of HI titers before and one month after receipt of TIV/placebo. Subjects were followed up for 11 months with symptom diaries, and respiratory specimens were collected during acute respiratory illnesses to permit confirmation of influenza virus infections. We found that previous vaccination was associated with reduced antibody responses to TIV against seasonal A(H1N1) and A(H3N2) particularly in children 9–17 y of age, but increased antibody responses to the same lineage of influenza B virus in children 6–8 y of age. Serological responses to the influenza A vaccine viruses were high regardless of vaccination history. One dose of TIV appeared to be efficacious against confirmed influenza B in children 6–8 y of age regardless of vaccination history.ConclusionsPrior vaccination was associated with lower antibody titer rises following vaccination against seasonal influenza A vaccine viruses, but higher responses to influenza B among individuals primed with viruses from the same lineage in preceding years. In a year in which influenza B virus predominated, no impact of prior vaccination history was observed on vaccine efficacy against influenza B. The strains that circulated in the year of study did not allow us to study the effect of prior vaccination on vaccine efficacy against influenza A.

The influence of influenza virus infections on the development of tuberculosis

Recently, it was shown that interferon-γ mediated immune responses, which play a major role in the control of infection with Mycobacterium tuberculosis (Mtb), can be inhibited by type I interferons. Since type I interferons are abundantly induced during viral infections, we hypothesized that infections with influenza viruses might play a role in the development of active TB disease either directly after exposure to Mtb or through reactivation of latent Mtb infection. To explore this hypothesis we investigated in a retrospective study whether newly diagnosed adult tuberculosis patients from Indonesia had had recent influenza infection. Plasma samples from TB patients and controls were assayed for antibodies against two subtypes of at that time relevant, seasonal influenza A viruses. Overall, no correlation was observed with the presence of antibodies and manifest tuberculosis. Still, antibody titers against circulating A/H3N2 influenza virus were slightly enhanced in tuberculosis patients as compared to controls, and highest in cases of advanced tuberculosis. This suggests that tuberculosis patients were recently infected with influenza, before clinical manifestation of the disease. Alternatively, the production of antibodies and susceptibility to tuberculosis may be influenced by a common confounding factor, for example the ability of patients to induce interferon-α. We conclude that in an endemic country like Indonesia, an influenza virus infection is not a major determinant for developing clinically manifest tuberculosis.

Effect of Oseltamivir Carboxylate Consumption on Emergence of Drug-Resistant H5N2 Avian Influenza Virus in Mallard Ducks

Oseltamivir carboxylate (OC) has been detected in environmental waters at various levels during recent influenza seasons in humans, reflecting levels of usage and stability of this drug. In consideration of the role of waterfowl as hosts for influenza viruses that may contribute to human infections, we evaluated the effect of consumption of low doses of OC on development of oseltamivir-resistant influenza virus mutants in mallard ducks (Anas platyrhynchos) infected with two different low-pathogenic (LP) H5N2 avian influenza viruses (AIV). We detected development of virus variants carrying a known molecular marker of oseltamivir resistance (neuraminidase E119V) in 4 out of 6 mallards infected with A/Mallard/Minnesota/182742/1998 (H5N2) and exposed to 1,000 ng/liter OC. The mutation first appeared as a minor population on days 5 to 6 and was the dominant genotype on days 6 to 8. Oseltamivir-resistant mutations were not detected in virus from ducks not exposed to the drug or in ducks infected with a second strain of virus and similarly exposed to OC. Virus isolates carrying the E119V mutation displayed in vitro replication kinetics similar to those of the wild-type virus, but in vivo, the E119V virus rapidly reverted back to wild type in the absence of OC, and only the wild-type parental strain was transmitted to contact ducks. These results indicate that consumption by wild waterfowl of OC in drinking water may promote selection of the E119V resistance mutation in some strains of H5N2 AIV that could contribute to viruses infecting human populations.

Comparison of 3 School-Based Influenza Surveillance Indicators

Early in the 2009 pandemic influenza A (H1N1) experience, children aged 5 to 17 years were determined to be disproportionately affected compared with recent influenza seasons. To characterize the pandemic among school-aged children, to enable timely influenza outbreak identification, and to determine which school-based influenza surveillance indicator correlated most closely with a laboratory-based standard influenza indicator (standard) and, therefore, might be most useful for future school-based influenza surveillance. : During the 2009-2010 school year, we monitored students using 3 different surveillance indicators: (1) all-cause absenteeism, (2) influenza-like illness (ILI)-related absenteeism, (3) and ILI-related school health office visits. Thresholds were set for each indicator to identify individual school outbreaks. Each surveillance indicator was compared with the standard, confirmed influenza cases among hospitalized patients. Tri-County (Denver metropolitan area), Colorado. Prekindergarten through 12th-grade students in public schools. Correlation coefficients comparing each influenza surveillance indicator with the standard and graphs comparing weekly rates for each influenza surveillance indicator or weekly outbreak counts with the standard. Correlation between the surveillance indicators and the standard varied greatly. All-cause absenteeism correlated most poorly with the standard (Pearson's r = 0.33) and ILI-related health office visits correlated moderately well (r = 0.63). Influenza-like illness-related absenteeism correlated best (r = 0.92) and could be improved (r = 0.97) by shifting ILI-absenteeism data later by 1 week. Graphs of weekly rates or weekly outbreak counts also illustrated that ILI-related absenteeism correlated best with the standard. For influenza surveillance among school-aged children, when feasible, we recommend using ILI-related absenteeism, which correlated best and its rate peaked more than 1 week sooner than the standard. The other 2 surveillance indicators might be useful in certain situations, such as when resources are limited.

Short communication: isolation and phylogenetic analysis of an avian-origin H3N2 canine influenza virus in dog shelter, China

A H3N2 canine influenza virus, A/canine/Guangdong/3/2011 (H3N2), was isolated from roaming dogs in rural China. Sequence and phylogenetic analysis of eight gene segments revealed that the A/canine/Guangdong/3/2011 (H3N2) was most similar to a recent H3N2 canine influenza virus isolated in cats from South Korea, which originated from an avian strain. To our knowledge, this is the first report of an avian-origin H3N2 CIV which was isolated from roaming dogs in China. The epidemiologic information provided herein suggests that continued study is required to determine if this virus could be established in the roaming dog population in rural China and pose potential threats to public health.

Effect of the 2009 Influenza A(H1N1) Pandemic on Invasive Pneumococcal Pneumonia

Because pneumococcal pneumonia was prevalent during previous influenza pandemics, we evaluated invasive pneumococcal pneumonia (IPP) rates during the 2009 influenza A(H1N1) pandemic. We identified laboratory-confirmed, influenza-associated hospitalizations and IPP cases (pneumococcus isolated from normally sterile sites with discharge diagnoses of pneumonia) using active, population-based surveillance in the United States. We compared IPP rates during peak pandemic months (April 2009-March 2010) to mean IPP rates in nonpandemic years (April 2004-March 2009) and, using Poisson models, to 2006-2008 influenza seasons. Higher IPP rates occurred during the peak pandemic month compared to nonpandemic periods in 5-24 (IPP rate per 10 million: 48 vs 9 (95% confidence interval [CI], 5-13), 25-49 (74 vs 53 [CI, 41-65]), 50-64 (188 vs 114 [CI, 85-143]), and ≥65-year-olds (229 vs 187 [CI, 159-216]). In the models with seasonal influenza rates included, observed IPP rates during the pandemic peak were within the predicted 95% CIs, suggesting this increase was not greater than observed with seasonal influenza. The recent influenza pandemic likely resulted in an out-of-season IPP peak among persons ≥5 years. The IPP peak's magnitude was similar to that seen during seasonal influenza epidemics.

Interaction of Influenza A/H1N1pdm Virus with Human Neuronal and Ocular Cells

Background: Influenza virus is a highly prevalent respiratory virus responsible for annual epidemics as well as occasional pandemics. Extra respiratory complications have been described, including neurological as well as ocular complications. This study examines the permissiveness of a panel of human neuronal and ocular cells to infection with the recent influenza A/H1N1pdm virus and cellular expression of α2,3- and α2,6-linked sialic acids. Methods: Studied cells included the human neuroblastoma cell lines SH-SY5YplkOB1 and SK-N-SH, a glioblastoma patient isolate GBM847a, the human uveal melanoma cell lines OCM3, OMM1.5 and 92-1, and, as controls, Madin-Darby canine kidney (MDCK) and 16HBE human bronchial epithelial cells. Cells were infected with influenza A/H1N1pdm virus and their permissiveness was assessed via nucleoprotein (NP) staining analyzed by fluorescence microscopy. Additionally, cells were stained for the presence of α2,3- and α2,6-linked sialic acids and examined by fluorescence microscopy as well. Results: All tested human cell types were permissive for influenza A/H1N1pdm infection. Furthermore, selected neuronal and ocular cells expressed α2,3- and/or α2,6-linked sialic acids. Discussion: This study demonstrates the permissiveness of a panel of human neuronal and ocular cells for the recent influenza A/H1N1pdm virus and expression of α2,3-and α2,6-linked sialic acids. These data contribute to clinical as well as experimental evidence indicating that, apart from respiratory cells; influenza virus can infect other cells and, thus, may give rise to extra respiratory complications.

The role of atypical microorganisms and viruses in severe acute community-acquired pneumonia

RésuméL’attention des réanimateurs n’est guère attirée par les bactéries atypiques ou les virus dans le cadre des pneumonies communautaires sévères. Seules classiquement, Legionella pneumophila et les virus influenza, du fait de la pandémie grippale récente H1N1, restent présents dans la réflexion diagnostique. Pourtant, les pneumonies bactériennes atypiques ne sont pas rares, représentant jusqu’à 44 % des pneumonies communautaires. Considérées comme moins sévères que les pneumonies à bactéries pyogènes « typiques », 25 % d’entre elles justifient une hospitalisation, et 15 % présentent des critères de sepsis sévères. Si Legionella pneumophila est plus fréquemment en cause dans les formes graves, Mycoplasma pneumoniae peut être responsable de véritables défaillances multiviscérales. Les outils diagnostiques sont aujourd’hui performants (antigénurie légionelle et recherche en polymerase chain reaction [PCR] de mycoplasme en particulier) et permettent un diagnostic rapide et précoce. Le traitement est bien codifié et repose sur les macrolides ou les fluoroquinolones, en association dans les formes graves de légionellose. Le rôle des virus au cours des pneumonies communautaires sévères, seuls ou associés à des bactéries, devient de plus en plus établi grâce aux méthodes de diagnostic rapide de biologie moléculaire. Ces techniques ont permis la mise en évidence dans ces pneumonies de nombreux et nouveaux virus. Toute la question est désormais à l’imputabilité clinique de ces résultats biologiques très performants et donc à la décision d’instaurer ou non un traitement antiviral dont l’efficacité dans les formes sévères reste discutable.

Cross talk between animal and human influenza viruses.

Although outbreaks of highly pathogenic avian influenza in wild and domestic birds have been posing the threat of a new influenza pandemic for the past decade, the first pandemic of the twenty-first century came from swine viruses. This fact emphasizes the complexity of influenza viral ecology and the difficulty of predicting influenza viral dynamics. Complete control of influenza viruses seems impossible. However, we must minimize the impact of animal and human influenza outbreaks by learning lessons from past experiences and recognizing the current status. Here, we review the most recent influenza virology data in the veterinary field, including aspects of zoonotic agents and recent studies that assess the pandemic potential of H5N1 highly pathogenic avian influenza viruses.

The Epidemiology of the First Wave of H1N1 Influenza Pandemic in Aus-tralia: A Population-Based Study

Objectives: Following the recent H1N1 influenza pandemic we were able to describe seropositivity in a repre-sentative sample of adults prior to the availability of a specific vaccine.

Attack Rates Assessment of the 2009 Pandemic H1N1 Influenza A in Children and Their Contacts: A Systematic Review and Meta-Analysis

BackgroundThe recent H1N1 influenza A pandemic was marked by multiple reports of illness and hospitalization in children, suggesting that children may have played a major role in the propagation of the virus. A comprehensive detailed analysis of the attack rates among children as compared with their contacts in various settings is of great importance for understanding their unique role in influenza pandemics.Methodology/Principal FindingsWe searched MEDLINE (PubMed) and Embase for published studies reporting outbreak investigations with direct measurements of attack rates of the 2009 pandemic H1N1 influenza A among children, and quantified how these compare with those of their contacts. We identified 50 articles suitable for review, which reported school, household, travel and social events. The selected reports and our meta-analysis indicated that children had significantly higher attack rates as compared to adults, and that this phenomenon was observed for both virologically confirmed and clinical cases, in various settings and locations around the world. The review also provided insight into some characteristics of transmission between children and their contacts in the various settings.Conclusion/SignificanceThe consistently higher attack rates of the 2009 pandemic H1N1 influenza A among children, as compared to adults, as well as the magnitude of the difference is important for understanding the contribution of children to disease burden, for implementation of mitigation strategies directed towards children, as well as more precise mathematical modeling and simulation of future influenza pandemics.

Influenza in Africa: Uncovering the Epidemiology of a Long-Overlooked Disease

Influenza is a well-documented cause of morbidity and mortality in high- and middle-income countries. In the past few decades and particularly during the recent influenza pandemic, numerous studies and surveillance reports in the United States, Europe, Australia, and parts of Asia have improved our understanding of the epidemiology and burden of influenza in those regions. In Africa, however, the picture is quite different. Until the latter half of the last decade minimal effort had been made to understand the epidemiology, burden, and seasonality of influenza in Africa, a continent where some of the poorest populations in the world reside; where human immunodeficiency virus (HIV) infection and AIDS, tuberculosis, and malaria have long ravaged residents; and where resources for health are scarce and often directed at securing basic healthcare and prevention measures. As a result, the impact of the disease in this region has been considered negligible [1].

Application of change point analysis to daily influenza-like illness emergency department visits

BackgroundThe utility of healthcare utilization data from US emergency departments (EDs) for rapid monitoring of changes in influenza-like illness (ILI) activity was highlighted during the recent influenza A (H1N1) pandemic. Monitoring has tended to rely on detection algorithms, such as the Early Aberration Reporting System (EARS), which are limited in their ability to detect subtle changes and identify disease trends.ObjectiveTo evaluate a complementary approach, change point analysis (CPA), for detecting changes in the incidence of ED visits due to ILI.Methodology and principal findingsData collected through the Distribute project (isdsdistribute.org), which aggregates data on ED visits for ILI from over 50 syndromic surveillance systems operated by state or local public health departments were used. The performance was compared of the cumulative sum (CUSUM) CPA method in combination with EARS and the performance of three CPA methods (CUSUM, structural change model and Bayesian) in detecting change points in daily time-series data from four contiguous US states participating in the Distribute network. Simulation data were generated to assess the impact of autocorrelation inherent in these time-series data on CPA performance. The CUSUM CPA method was robust in detecting change points with respect to autocorrelation in time-series data (coverage rates at 90% when −0.2≤ρ≤0.2 and 80% when −0.5≤ρ≤0.5). During the 2008–9 season, 21 change points were detected and ILI trends increased significantly after 12 of these change points and decreased nine times. In the 2009–10 flu season, we detected 11 change points and ILI trends increased significantly after two of these change points and decreased nine times. Using CPA combined with EARS to analyze automatically daily ED-based ILI data, a significant increase was detected of 3% in ILI on April 27, 2009, followed by multiple anomalies in the ensuing days, suggesting the onset of the H1N1 pandemic in the four contiguous states.Conclusions and significanceAs a complementary approach to EARS and other aberration detection methods, the CPA method can be used as a tool to detect subtle changes in time-series data more effectively and determine the moving direction (ie, up, down, or stable) in ILI trends between change points. The combined use of EARS and CPA might greatly improve the accuracy of outbreak detection in syndromic surveillance systems.

Quadrivalent Ann Arbor strain live-attenuated influenza vaccine

Influenza B is responsible for significant morbidity in children and adults worldwide. For more than 25 years, two antigenically distinct lineages of influenza B viruses, B/Yamagata and B/Victoria, have cocirculated globally. Current influenza vaccine formulations are trivalent and contain two influenza subtype A strains (A/H1N1 and A/H3N2) but only one B strain. In a half of recent influenza seasons, the predominant circulating influenza B lineage was different from that contained in trivalent influenza vaccines. A quadrivalent live-attenuated influenza vaccine (Q/LAIV) that contains two B strains, one from each lineage, has been developed to help provide broad protection against influenza B. Q/LAIV was recently approved for use in the USA in eligible individuals 2–49 years of age. This review summarizes clinical trial data in support of Q/LAIV.