Children aged 7–14 years in Novgorod, Russia, were given Russian live cold-adapted or inactivated influenza vaccines or placebo over a 2-year period. Schools were randomly assigned as a whole to one of the preparations. In the first year, the vaccines were bivalent, containing types A (H3N2) and A (H1N1) components. In the second year, the vaccines also contained a type B component. In the first year, all viruses isolated were type A (H3N2); in the second, about three-quarters of the isolates were type B and the rest type A (H1N1). During both years, the vaccines protected the vaccinated children. Where significant differences existed, the live attenuated vaccine was more protective than the inactivated. Vaccination rates in schools in which live attenuated vaccines had been used were inversely related to illness rates of staffand unvaccinated children, suggesting that viral transmission had been reduced by the vaccine.

The majority of seasonal influenza vaccines are trivalent, containing two A virus strains (H1N1 and H3N2) and one B virus strain. The co-circulation of two distinct lineages of B viruses can lead to mismatch between the influenza B virus strain recommended for the trivalent seasonal vaccine and the circulating B virus. This has led some manufacturers to produce quadrivalent influenza vaccines containing one strain from each B lineage in addition to H1N1 and H3N2 strains. However, it is also important to know whether vaccines containing a single influenza B strain can provide cross-protectivity against viruses of the antigenically distinct lineage. The aim of this study was to assess in naïve ferrets the potential cross-protective activity of trivalent live attenuated influenza vaccine (T-LAIV) against challenge with a heterologous wild-type influenza B virus belonging to the genetically different lineage and to compare this activity with effectiveness of quadrivalent LAIV (Q-LAIV) in the ferret model. Ferrets were vaccinated with either one dose of trivalent LAIV containing B/Victoria or B/Yamagata lineage virus, or quadrivalent LAIV (containing both B lineages), or placebo. They were then challenged with B/Victoria or B/Yamagata lineage wild-type virus 28 days after vaccination. The ferrets were monitored for clinical signs and morbidity. Nasal swabs and lung tissue samples were analyzed for the presence of challenge virus. Antibody response to vaccination was assessed by routine hemagglutination inhibition assay. All LAIVs tested were found to be safe and effective against wild-type influenza B viruses based on clinical signs, and virological and histological data. The absence of interference between vaccine strains in trivalent and quadrivalent vaccine formulations was confirmed. Trivalent LAIVs were shown to have the potential to be cross-protective against infection with genetically different influenza B/Victoria and B/Yamagata lineages. In this ferret model, quadrivalent vaccine provided higher protection to challenge against both B/Victoria and B/Yamagata lineage viruses. However, T-LAIV provided some cross-protection in the case of a mismatch between circulating and vaccine type B strains. Notably, B/Victoria-based T-LAIV was more protective compared to B/Yamagata-based T-LAIV.

Introduction: Live attenuated influenza vaccines (LAIVs) have been in use for more than three decades and are now licensed in many countries. There is evidence that LAIVs can have greater efficacy than inactivated influenza vaccines, especially against mismatched influenza, however, in recent years, a number of trials have found a lack of LAIV efficacy, mainly in relation to the H1N1 virus. Areas covered: In this review, we summarize the results of clinical research published in the past 5 years on the immunogenicity of LAIVs, with special attention to the mechanisms of establishing protective immunity and some factors that may influence immunogenicity and efficacy. Expert opinion: A number of recent clinical studies confirmed that the immune responses to LAIVs are multifaceted, involving different immune mechanisms. These trials suggest that the intrinsic replicative properties of each LAIV component should be taken into account, and the precise effects of adding a fourth vaccine strain to trivalent LAIV formulations are still to be identified. In addition, new data are emerging regarding the impact of pre-vaccination conditions, such as pre-existing immunity or concurrent asymptomatic viral and bacterial respiratory infections, on LAIV immunogenicity, suggesting the importance of monitoring them during clinical trials or vaccination campaigns.

A wide diversity of zoonotic viruses that are capable of overcoming host range barriers facilitate the emergence of new potentially pandemic viruses in the human population. When faced with a new virus that is rapidly emerging in the human population, we have a limited knowledge base to work with. The pandemic invasion of the new SARS-CoV-2 virus in 2019 provided a unique possibility to quickly learn more about the pathogenesis of respiratory viruses. In this review, the impact of pandemics on the circulation of seasonal respiratory viruses is considered. The emergence of novel respiratory viruses has often been accompanied by the disappearance of existing circulating strains. Some issues arising from the spread of pandemic viruses and underlying the choices of a strategy to fight the coronavirus infection are discussed.

A wide variety of zoonotic viruses that can cross the interspecies barrier promote the emergence of new, potentially pandemic viruses in the human population that is often accompanied by the disappearance of existing circulating strains. Among the various reasons underlying this phenomenon is the strengthening of herd immunity by expanding the immune layer of population and improving means and methods of medical care. However, natura abhorret vacuum, and new pathogens come to replace disappearing ones. Over the past ten years, humanity has faced two pandemics: swine flu A(H1N1)pdm09 in 2009 and COVID-19 in 2019, providing scientists with a unique opportunity to learn more about a relationship between respiratory viruses and their pathogenesis. Together with viruses of pandemic significance, a large number of seasonal respiratory viruses circulate, which contribute to the structure of human morbidity, and coinfections aggravate the condition of the illness. In the conditions of the spread of new viruses with unexplored characteristics, in the absence of means of prevention and therapy, it is especially important to prevent the aggravation of morbidity due to mixed infections. Here we review the mutual involvement of pandemic influenza A(H1N1)pdm09 and SARS-CoV-2 coronavirus and seasonal respiratory viruses in the epidemic process, discuss some issues related to their spread, potential causes affecting the spread and severity of the morbidity. The given facts testify to the existence of seasonality and temporal patterns of the beginning and end of respiratory viruses circulation. Interestingly, the beginning of circulation of the pandemic influenza A(H1N1)pdm09 virus led to a shift in the timing and intensity of circulation of some respiratory viruses, which is probably caused by existence of “replication conflicts” between them, and did not affect others. Coinfection with SARS-CoV-2-19 and other respiratory viruses, especially respiratory syncytial virus and rhinoviruses, was quite often observed. At the current stage, no aggravating effect of influenza on the course of COVID-19 in mixed infection has been established. Whether this is due to the mild course of influenza infection in the 2020 epidemic season, or the competitive impact of SARS-CoV-2 on influenza viruses is not yet clear. Experts are still at the stage of accumulating facts and working on creating means of effective prevention and treatment of the new coronavirus infection.