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 preexisting immunity or concurrent asymptomatic viral and bacterial respiratory infections, on LAIV immunogenicity, suggesting the importance of monitoring them during clinical trials or vaccination campaigns.
Keywords: Live attenuated influenza vaccine; antibody immune response; cell-mediated immune response; clinical trial; correlate of protection; immunogenicity.