With the exception of the very young children (<3 years old), many individuals aged 3 years or older had significantly higher pre-vaccination MN titers against egg-propagated A(H3N2) viruses than cell-propagated A(H3N2) viruses (Figure 2), suggesting antibody targeting HA egg-adapted sites preexisted. reactions were observed between male and female vaccinees. Here, the combination of age-specific reactions to vaccine egg-adapted substitutions, varied host immune priming histories, and computer virus antigenic drift affected antibody reactions following vaccination and may have led to the low and variable VE against A(H3N2) viruses across different age groups. Keywords: Infectious disease, Vaccines Keywords: Influenza Intro Influenza viruses continue to GSK1059615 cause high morbidity and mortality yearly. Amid the current pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viruses and influenza/SARS-CoV-2 cocirculation, influenza vaccination has become especially important. Vaccination is the most effective public health Rabbit Polyclonal to OR2B6 measure to combat influenza, however, the constant genetic and antigenic drift of influenza viruses requires annual updates of seasonal influenza vaccine parts. In the United States, evaluation of seasonal influenza vaccine performance (VE) based on the test-negative design has been conducted annually since the 2004C05 influenza time of year (1). Decreased VE can occur when mainly circulating viruses possess antigenically drifted from your vaccine viruses, such as the low VE reported for any(H3N2) during the 2014C15 time of year (2). Currently, most licensed influenza vaccines are still produced in chicken eggs, which can expose substitutions in the hemagglutinins (HAs) of the viruses as a result of egg adaptation. Egg-adapted substitutions occurred in multiple HA epitopes of recent egg-based A(H3N2) vaccines. These included substitutions from threonine (T) to lysine (K) at HA amino acid position 160 (T160K), and from leucine (L) to proline (P) at position 194 (L194P) at antigenic site B, which can alter the antigenicity of these vaccines (2C8). Levine et al. reported that during the 2017C18 influenza time of year, adult serum antibody titers against circulating viruses, but not egg-adapted A(H3N2) vaccines, correlated with safety against influenza infections (9). Therefore, egg-adapted changes in HA are thought to be another form of antigenic mismatch between vaccine computer virus GSK1059615 and circulating strains (6). In recent years, it has also become apparent that, even within the same influenza time of year for the same subtype of viruses, VE can still vary greatly among different age groups. This is likely due to the complex exposure history to influenza illness or vaccination in humans, including initial child years immune priming (10C15). Immune priming can play significant functions in shaping an individuals antibody reactions to newer influenza viruses later in existence and impact vaccine reactions (11C14). Birth cohort effects on age-specific VE have been reported for both A(H1N1)pdm09 and A(H3N2) (13, 16, 17). Additional factors or a compounding effect of multiple factors may also contribute to the variations in observed VE. Such as, compared with the 2016C17 influenza time of year, in 2017C18, even though the A(H3N2) vaccine remained unchanged and there was no obvious antigenic drift of GSK1059615 circulating A(H3N2) viruses, a higher hospitalization rate due to A(H3N2) infections was reported, and a reduced VE was observed in seniors groups, but not in very young children (4, 18). Further studies are needed to fully understand the age-related variations in VE in order to design effective vaccination strategies for different age groups, especially for those who are at higher risk of influenza illness. In GSK1059615 the 2016C17 to 2018C19 influenza months, A(H3N2) vaccine viruses were antigenically related, but the reported VE assorted GSK1059615 between months and across different age groups (4, 7, 19). This offered an opportunity to investigate the underlying immune mechanism that may have contributed to the difference in VE. Here, we analyzed pre- and post-vaccination sera collected over 3 influenza months from a wide age range (from 7 weeks to 82 years) of cohorts who received quadrivalent egg-based, inactivated (QIV) vaccines. We compared age-related preexisting immunity and its impact on vaccine-induced antibody reactions across 6 age groups. We also constructed reverse genetic (RG) viruses that had individual egg-adapted substitutions.