Impact of age and pre-existing immunity on the induction of human antibody responses against influenza B viruses

Abstract

Pre-existing immunity to influenza is dependent on a number of factors and can vary greatly within and across influenza subtypes. In this study, volunteers (aged 18–85 years) were vaccinated with split, inactivated FluzoneTM in four consecutive influenza seasons from 2013 to 2016. The impact of repeat vaccination on breadth and durability of functional antibodies was assessed for total IgG and IgA anti-hemagglutinin (HA) binding antibodies and hemagglutination-inhibition (HAI) activity against both influenza B lineages. Many subjects were able to maintain high seroprotective titers to the vaccine strains in subsequent years, which resulted in low vaccine-induced seroconversion rates. This was especially evident in younger subjects who typically had higher titers and maintained these titers into the following season. In contrast, the HAI titers in elderly subjects were generally lower and more likely to decline prior to the start of the next influenza season. Immunological recall or ‘back-boosting’ to antigenically related viruses was associated with seroconversion. Overall, influenza vaccination in both younger and older people elicited broadly reactive immune responses within a lineage, as well as cross-reactive immune responses between lineages. This study exemplified the impact that age and influenza exposure history have on determining an individual’s ability to respond to future influenza infections.

Preexisting subtype immunodominance shapes memory B cell recall response to influenza vaccination

“…Due to low IBV sensitivity in the HAI test, viruses underwent ether treatment as recommended by the influenza division of the CDC in order to increase assay sensitivity, and more reliable detection of HAI rises following influenza B vaccination (52). Ether-extracted split viruses were created from freshly harvested allantoic fluid and from previously frozen virus lots, prior to HA and HAI assays, as previously described (77). Briefly, viruses were mixed at a 1:1 ratio with anhydrous diethyl ether (ACROS Organics, Thermo Fisher Scientific) for ≥ 4 hours, with stirring.…”

“…Statistics. Subjects were grouped by age as previously described (77) or serological changes in HAI activity to the 4 vaccine components calculated as f(HAI) = log_2(HAId21/HAId0) H1N1 + log_2(HAId21/ HAId0) H3N2 + log_2(HAId21/HAId0) Bvic + log_2(HAId21/HAId0) Byam . Subjects with f(HAI) < 4 were defined as nonresponders, subjects with 4 < f(HAI) < 8 were defined as low responders and subjects f(HAI) > 8 were defined as high responders.…”

Immune Imprinting in the Influenza Ferret Model

“…This back-boosting, also described as an anamnestic response, has been observed in the human population [112][113][114][115] and has been recapitulated within the ferret model. This similarity makes it a useful tool for determining vaccine performance in a setting where back-boosting is present [37].…”

“…This back-boosting is what contributed to the difference in the naïve vs. pre-immune antigenic maps of different A(H3N2) viruses [79]. The exact mechanism of back-boosting is not completely elucidated [113].…”

Vaccines to Prevent Infectious Diseases in the Older Population: Immunological Challenges and Future Perspectives

“…With age influenza-specific antibody titers decline faster leading to loss of seroprotection until the following season and possibly rendering vaccinees susceptible to some influenza strains even toward the end of the same season (38,39). To overcome the lower influenza efficacy in the elderly high-dose, adjuvanted and intradermally administered vaccines have been developed and are in clinical use.…”