Selecting the B strain for inclusion in a trivalent seasonal influenza vaccine has been difficult because two distinct influenza B lineages frequently co-circulate, prompting consideration of a quadrivalent vaccine containing two A and two B strains. Because interference among wild-type influenza viruses is a well-documented phenomenon and viral replication is required to elicit protection by the licensed live-attenuated influenza vaccine (LAIV; MedImmune, LLC, Gaithersburg, MD, USA), a potential quadrivalent formulation raises considerations of interference among the LAIV strains contained in the vaccine. We reviewed the available clinical and nonclinical literature to understand the potential impact of viral interference on immunogenicity, efficacy and shedding of LAIV strains. We have found no clinically significant evidence of viral or immune interference affecting efficacy of LAIV strains in multivalent vaccine formulations. Future clinical studies should compare the safety and immune responses of children and adults to licensed trivalent and investigational quadrivalent LAIV formulations.

Live attenuated influenza vaccine (LAIV) has been available as a trivalent formulation in the EU since 2012. Influenza B strains from two lineages have co-circulated outside Asia in Europe, Israel and North America since the early 2000s. The trivalent vaccine contained a single influenza B lineage virus chosen primarily on the basis of the previous year's circulating lineage. Failure to align the vaccine virus with the circulating virus leaves even vaccinated patients, particularly children, at risk for infection with B viruses from the other lineage. Recently, a tetravalent formulation was approved and use will begin during the 2014-2015 influenza season. Approval of LAIV Tetra was based on the established efficacy and safety of trivalent LAIV and studies demonstrating similar immunogenicity between the trivalent and tetravalent vaccines. Addition of a fourth strain to the vaccine will address the issue of co-circulation of influenza B viruses and provide a broader range of protection.

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Introduction: Asthma is one of the most common chronic respiratory conditions worldwide and can be exacerbated by influenza. Findings from early trials demonstrated a higher risk of medically significant wheezing in otherwise healthy young children (aged 6−23 months) following administration of the Ann Arborbackbone live attenuated influenza vaccine (LAIV-AA). In more recent years, several additional studies have investigated the safety of LAIV-AA in older children (2−17 years of age) and adults with asthma or prior wheezing, but these findings have not yet been systematically evaluated. Areas covered:We conducted a systematic literature review to assess and synthesize the evidence from all available studies on the safety of LAIV-AA in people aged 2−49 years with a diagnosis of asthma or recurrent wheezing. Expert opinion:Fourteen studies over 20 years, involving a total of 1.2 million participants, provided evidence that LAIV-AA was well tolerated with no safety concerns in individuals aged 2−49 years with a diagnosis of asthma or recurrent wheezing. These data can help inform guidelines for use of LAIV-AA in children and adults with a history of asthma or recurrent wheezing.

Background Given the substantial burden of influenza in the pediatric population, influenza vaccination with live attenuated influenza vaccines (LAIVs) and/or inactivated influenza vaccines (IIVs) is now recommended for children in an increasing number of countries. In recent seasons, the real-world effectiveness of influenza vaccines has varied substantially. In the 2013/14 and 2015/16 influenza seasons, LAIV demonstrated reduced vaccine effectiveness (VE) against A/H1N1 strains. LAIV and IIVs have also demonstrated variable effectiveness against A/H3N2 strains in recent seasons. This study evaluated LAIV and IIV effectiveness in children between the 2016/17 and 2018/19 seasons. Methods Quadrivalent LAIV (LAIV4) and IIV effectiveness studies conducted in the pediatric population from 2016/17 through 2018/19 were identified from published literature, congress presentations, public health websites and personal communication with national investigators. Studies were excluded if they were from countries where Ann Arbor-backbone LAIV was not available for at least one season during the study period, were from randomized, interventional studies, or contained duplicate data from other publications. Results For the three seasons, point estimates of all-strain VE for children ranged from 20% to 74% for LAIV4 and from –20% to 68% for IIV (Fig 1A). During the same period, VE against A/H3N2 for children ranged from –76% to 74% for LAIV4 and from 3% to 56% for IIV (Fig 1B). Point estimates of VE against A/H1N1 for children were 50% and 90% for LAIV4 and ranged from 24% to 87% for IIV (Fig 1C). For influenza B, VE for children ranged from 31% to 80% for LAIV4 and from –12% to 80% for IIV (Fig 1D). Statistical comparison of LAIV4 and IIV VE across each season was not feasible due to the multivariate nature of each study cohort. Figure 1. 2016–2019 Effectiveness of Inactivated and Live Attenuated Influenza Vaccines by Influenza Strain in Children Conclusion During three recent seasons, LAIV4 and IIV showed similar moderate effectiveness against all influenza strains, A/H1N1 strains, and B strains. VE against A/H3N2 for LAIV4 and IIV was good in 2016/17, but decreased in the 2017/18 and 2018/19 seasons. VE estimates for LAIV4 and IIV overlapped for all strains and each subtype, demonstrating the general comparability of LAIV4 and IIV VE in the seasons between 2016 and 2019. Disclosures Allyn Bandell, PharmD, AstraZeneca (Employee, Shareholder) Raburn Mallory, MD, AstraZeneca (Employee, Shareholder) Christopher S. Ambrose, MD, MBA, AstraZeneca (Employee, Shareholder)