Prime-boost, double-dose immunization and immunity to influenza vaccination in COPD

Abstract

<b>Background:</b> COPD patients are more susceptible to viral respiratory infections and their sequelae and have intrinsically weaker immune responses to vaccinations against influenza and other pathogens. Prime-Boost Double-Dose immunization has been suggested as a general strategy to overcome weak humoral response to vaccines, including in susceptible populations with weak immunity, but has not been formally studied in COPD influenza vaccine responses. <b>Methods:</b> Following guideline recommendations during 2018 to double vaccine dose in COPD patients, we conducted an open label study of seasonal influenza vaccination in 33 COPD patients (mean age 70 yrs (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 mg haemagglutinin per strain) in a prime-boost schedule 28 days apart. We measured strain-specific antibody titres and induction of strain specific B-cell responses following the prime and boost immunizations. <b>Results:</b> Whereas priming immunization induced a predictable increase in strain-specific antibody titres, a second booster dose was strikingly ineffective at further increasing antibody titres. Similarly, priming immunization 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. <b>Conclusions:</b> Prime-Boost Double-Dose immunization does not improve influenza vaccine immunogenicity in vaccine experienced COPD patients. These finding underscore the need to design more effective vaccine strategies for COPD patients for influenza.