TY - JOUR T1 - Prime-boost, double-dose influenza vaccine immunity in COPD: a pilot observational study JF - ERJ Open Research JO - erjor DO - 10.1183/23120541.00641-2021 SP - 00641-2021 AU - Gary P. Anderson AU - Louis B. Irving AU - Andrew Jarnicki AU - Katherine Kedzierska AU - Marios Koutsakos AU - Stephen Kent AU - Aeron C. Hurt AU - Adam K. Wheatley AU - Thi H. O. Nguyen AU - Natale Snape AU - John W. Upham Y1 - 2022/01/01 UR - http://openres.ersjournals.com/content/early/2022/08/11/23120541.00641-2021.abstract N2 - Rationale COPD patients are more susceptible to viral respiratory infections and their sequalae and have intrinsically weaker immune responses to vaccinations against influenza and other pathogens. Prime-Boost Double-Dose immunisation has been suggested as a general strategy to overcome weak humoral response to vaccines, such as seasonal influenza vaccination, in susceptible populations with weak immunity. However this strategy, which may also provide fundamental insights into the nature of weakened immunity, has not been formally studied in COPD.Methods We conducted an open label study of seasonal influenza vaccination in 33 vaccine-experienced COPD patients recruited from established cohorts (mean age 70 years (66.9–73.2); mean FEV1/FVC ratio 53.4% (48.0–58.8)). Patients received two sequential standard doses of the 2018 quadrivalent influenza vaccine (15 μg haemagglutinin per strain) in a prime-boost schedule 28 days apart. We measured strain-specific antibody titres, an accepted surrogate of likely efficacy, and induction of strain specific B-cell responses following the prime and boost immunisations.Measurements and Main Results Whereas priming immunisation induced the expected increase in strain-specific antibody titres, a second booster dose was strikingly ineffective at further increasing antibody titres. Similarly, priming immunisation induced strain-specific B cells, but a second booster dose did not further enhance the B cell response. Poor antibody responses were associated with male gender and cumulative cigarette exposure.Conclusions Prime-Boost Double-Dose immunisation does not further improve influenza vaccine immunogenicity in previously vaccinated COPD patient. These finding underscore the need to design more effective vaccine strategies for COPD patients for influenza.FootnotesThis manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.Conflict of interest: All Authors declare no conflict of interest. ER -