Safety of live attenuated influenza vaccine (LAIV) in children with moderate to severe asthma

Abstract

Background: Live attenuated influenza vaccine (LAIV) is recommended for annual influenza vaccination in children from age 2 years. However, some guidelines recommend against its use in children with asthma or recurrent wheeze due to concerns over its potential to induce wheezing. Objective: We sought to assess the safety of LAIV in children with moderate to severe asthma, and in preschool children with recurrent wheeze. Methods: Prospective, multicenter, open-label, phase IV intervention study in 14 specialist UK clinics. LAIV was administered under medical supervision, with follow-up of asthma symptoms 72 hours and 4 weeks late, using validated questionnaires. Results: A total of 478 young people (median, 9.3; range, 2-18 years) with physician-diagnosed asthma or recurrent wheeze were recruited, including 208 (44%) prescribed high-dose inhaled corticosteroids and 122 (31%) with severe asthma. There was no significant change in asthma symptoms in the 4 weeks after administration (median change, 0; P 5 .26, McNemar test), with no impact of level of baseline asthma control/symptoms in predicting either a worsening of asthma or exacerbation after LAIV using a regression model. A total of 47 subjects (14.7%; 95% CI, 11%-19.1%) reported a severe asthma exacerbation in the 4 weeks after immunization, requiring a short course of systemic corticosteroids; in 4 cases, this occurred within 72 hours of vaccination. No association with asthma severity, baseline lung function, or asthma control was identified. Conclusions: LAIV appears to be well tolerated in the vast majority of children with asthma or recurrent wheeze, including those whose asthma is categorized as severe or poorly controlled.

Sequential delivery of LAIV and SARS-CoV-2 in the ferret model can reduce SARS-CoV-2 shedding and does not result in enhanced lung pathology

“…Mild histopathological changes in both the lungs and nasal turbinates were also noted in animals that received LAIV only (LAIV/Mock). LAIV has an excellent safety profile in clinical studies 19,29 , suggesting that this level of pathology resulted from LAIV induced immune response. This was likely due to the higher pathogenicity of wild type influenza virus relative to LAIV, in concert with a more severe COVID-19 disease model in mice.…”

“…However, the prevalence of COVID-19 and influenza coinfections rates varies across the literature 9,10 and the implications for disease severity are not fully understood. Stowe et al retrospectively analyzed data from 19.256 UK patients during the first COVID-19 wave and showed that SARS-CoV-observations were made in the mouse model, where sequential influenza and SARS-CoV-2 infection resulted in exacerbated disease pathology 12 .…”

“…FluMist/Fluenz LAIV, is intranasally administered, with vaccine virus replication occurring in the epithelial cells of the upper respiratory tract, resulting in generation of both humoral and cellular immune responses 16,17 . LAIV is primarily used in children, offering similar protection when compared with inactivated influenza vaccines [18][19][20][21][22][23] . With the advantage of intranasal, needle free administration, LAIV has also demonstrated an ability to reduce community influenza transmission 24 .…”

“…However, the prevalence of COVID-19 and influenza coinfections rates varies across the literature 9,10 and the implications for disease severity are not fully understood. Stowe et al retrospectively analyzed data from 19.256 UK patients during the first COVID-19 wave and showed that SARS-CoV-2 and influenza co-infections correlated with greater risk of severe illness and death, suggesting synergistic interaction between the viruses 11 . Similar (which was not certified by peer review) is the author/funder.…”

Protective Intranasal Immunization Against Influenza Virus in Infant Mice Is Dependent on IL-6

“…Although intramuscular administration of a polyvalent formulation of chemically inactivated or disrupted influenza virus is the most common type of vaccine for seasonal influenza both in adults and children (25), intranasal administration of a live attenuated influenza virus (LAIV) in the respiratory tract is also utilized as a method of vaccination (26). However, this formulation is restricted to children more than 2 years of age and adults (27,28) because of reports of increased risk of reactive airway disease (29,30) and increased concern over the presence of underlying asthma in young vaccine recipients (31,32). The factors underlying the relatively lower effectiveness of recent intranasal vaccination with live attenuated virus compared to intramuscular administration of inactivated virus in some flu seasons (33)(34)(35) remain incompletely understood.…”