Prime-boost, double-dose influenza vaccine immunity in COPD: a pilot observational study
- Gary P. Anderson1⇑,
- Louis B. Irving2,
- Andrew Jarnicki1,
- Katherine Kedzierska3,
- Marios Koutsakos3,
- Stephen Kent4,5,
- Aeron C. Hurt6,10,
- Adam K. Wheatley7,
- Thi H. O. Nguyen7,
- Natale Snape8 and
- John W. Upham9
- 1Lung Health Research Centre, Department of Biochemistry and Pharmacology, The University of Melbourne, Parkville, Victoria, Australia
- 2Department of Respiratory Medicine, The Royal Melbourne Hospital, Parkville, Victoria, Australia
- 3Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Victoria, Australia
- 4Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity and ARC Centre for Excellence in Convergent Bio-Nano Science and Technology, The University of Melbourne, Parkville
- 5Melbourne Sexual Health Clinic and Infectious Diseases Department, Alfred Hospital, Monash University Central Clinical School, Carlton, Victoria, Australia
- 6WHO Collaborating Centre for Reference and Research on Influenza, Victorian Infectious Diseases Reference Laboratory, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Victoria, Australia*
- 7Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Victoria, Australia
- 8Faculty of Medicine, The University of Queensland Diamantina Institute, Translational Research Institute, Queensland, Australia
- 9Faculty of Medicine, The University of Queensland Diamantina Institute, Translational Research Institute and Princess Alexandra Hospital, Queensland, Australia
- 10Present address of Dr Hurt. Department of Infectious Diseases, Roche Pharma Research & Early Development, Basel, Switzerland
- Corresponding author: Gary Anderson (gpa{at}unimelb.edu.au)
Abstract
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.
Footnotes
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Conflict of interest: All Authors declare no conflict of interest.
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- Received November 16, 2021.
- Accepted August 1, 2022.
- Copyright ©The authors 2022
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