The impact of repeated vaccination on influenza vaccine effectiveness: a systematic review and meta-analysis

BACKGROUND Conflicting results regarding the impact of repeated vaccination on influenza vaccine effectiveness (VE) may cause confusion regarding the benefits of receiving the current season's vaccine. METHODS We systematically searched MEDLINE, Embase, PubMed, and Cumulative Index to Nursing and Allied Health Literature from database inception to August 17, 2016, for observational studies published in English that reported VE against laboratory-confirmed influenza for four vaccination groups, namely current season only, prior season only, both seasons, and neither season. We pooled differences in VE (∆VE) between vaccination groups by influenza season and type/subtype using a random effects model. The study protocol is registered with PROSPERO (registration number: CRD42016037241). RESULTS We identified 3435 unique articles, reviewed the full text of 634, and included 20 for meta-analysis. Compared to prior season vaccination only, vaccination in both seasons was associated with greater protection against influenza H1N1 (∆VE = 26%; 95% CI, 15% to 36%) and B (∆VE = 24%; 95% CI, 7% to 42%), but not H3N2 (∆VE = 10%; 95% CI, -6% to 25%). Compared to no vaccination for either season, individuals who received the current season's vaccine had greater protection against H1N1 (∆VE = 61%; 95% CI, 50% to 70%), H3N2 (∆VE = 41%; 95% CI, 33% to 48%), and B (∆VE = 62%; 95% CI, 54% to 68%). We observed no differences in VE between vaccination in both seasons and the current season only for H1N1 (∆VE = 4%; 95% CI, -7% to 15%), H3N2 (∆VE = -12%; 95% CI, -27% to 4%), or B (∆VE = -8%; 95% CI, -17% to 1%). CONCLUSIONS From the patient perspective, our results support current season vaccination regardless of prior season vaccination. We found no overall evidence that prior season vaccination negatively impacts current season VE. It is important that future VE studies include vaccination history over multiple seasons in order to evaluate repeated vaccination in more detail.