Opposing Effects of Prior Infection versus Prior Vaccination on Vaccine Immunogenicity against Influenza A(H3N2) Viruses

• Published in: Viruses Vol. 14; no. 3; p. 470
• Main Authors: Fox, Annette, Carolan, Louise, Leung, Vivian, Phuong, Hoang Vu Mai, Khvorov, Arseniy, Auladell, Maria, Tseng, Yeu-Yang, Thai, Pham Quang, Barr, Ian, Subbarao, Kanta, Mai, Le Thi Quynh, van Doorn, H. Rogier, Sullivan, Sheena G.
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 25.02.2022; MDPI
• Subjects: Antibodies; Antibodies, Viral; Australia; Ethics; Health care; health services; Humans; Hypotheses; Immunogenicity; Immunogenicity, Vaccine; Immunological memory; infection; Infections; Influenza; Influenza A; Influenza A virus; Influenza A Virus, H3N2 Subtype; Influenza Vaccines; Influenza, Human - prevention & control; Medical personnel; memory; Mutation; pre-existing immunity; Seasons; Serology; Vaccination; Vaccines; Vaccines, Inactivated; Vietnam; Viruses; Australia; Vietnam; Southern Hemisphere; influenza; infection; memory; pre-existing immunity; antibodies; immunogenicity; vaccination
• DOI: 10.3390/v14030470
• ISSN: 1999-4915

Prior vaccination can alternately enhance or attenuate influenza vaccine immunogenicity and effectiveness. Analogously, we found that vaccine immunogenicity was enhanced by prior A(H3N2) virus infection among participants of the Ha Nam Cohort, Viet Nam, but was attenuated by prior vaccination among Australian Health Care Workers (HCWs) vaccinated in the same year. Here, we combined these studies to directly compare antibody titers against 35 A(H3N2) viruses spanning 1968–2018. Participants received licensed inactivated vaccines containing A/HongKong/4801/2014 (H3N2). The analysis was limited to participants aged 18–65 Y, and compared those exposed to A(H3N2) viruses circulating since 2009 by infection (Ha Nam) or vaccination (HCWs) to a reference group who had no recent A(H3N2) infection or vaccination (Ha Nam). Antibody responses were compared by fitting titer/titer-rise landscapes across strains, and by estimating titer ratios to the reference group of 2009–2018 viruses. Pre-vaccination, titers were lowest against 2009–2014 viruses among the reference (no recent exposure) group. Post-vaccination, titers were, on average, two-fold higher among participants with prior infection and two-fold lower among participants with 3–5 prior vaccinations compared to the reference group. Titer rise was negligible among participants with 3–5 prior vaccinations, poor among participants with 1–2 prior vaccinations, and equivalent or better among those with prior infection compared to the reference group. The enhancing effect of prior infection versus the incrementally attenuating effect of prior vaccinations suggests that these exposures may alternately promote and constrain the generation of memory that can be recalled by a new vaccine strain.