We introduce the antibody landscape, a method for the quantitative analysis of antibody-mediated immunity to antigenically variable pathogens, achieved by accounting for antigenic variation among pathogen strains. We generated antibody landscapes to study immune profiles covering 43 years of influenza A/H3N2 virus evolution for 69 individuals monitored for infection over six years and for 225 individuals pre- and post-vaccination. On infection and vaccination titers increased broadly, including previously encountered viruses far beyond the extent of cross-reactivity observed after a primary infection. We explored implications for vaccination, and found that use of an antigenically advanced virus had the dual benefit of inducing antibodies against both advanced and previous antigenic clusters. These results indicate that pre-emptive vaccine updates may improve influenza vaccine efficacy in previously-exposed individuals.

During the SARS-CoV-2 pandemic, multiple variants with differing amounts of escape from pre-existing immunity have emerged, causing concerns about continued protection. Here, we use antigenic cartography to quantify and visualize the antigenic relationships among 16 SARS-CoV-2 variants titrated against serum samples taken post-vaccination and post-infection with seven different variants. We find major antigenic differences caused by substitutions at positions 417, 452, 484, and possibly 501. B.1.1.529 (Omicron) showed the highest escape from all sera tested. Visualization of serological responses as antibody landscapes shows how reactivity clusters in different regions of antigenic space. We find changes in immunodominance of different spike regions depending on the variant an individual was exposed to, with implications for variant risk assessment and vaccine strain selection.

To gain insight into the age at which children become infected with influenza viruses for the first time, we analyzed the seroprevalence of antibodies against influenza viruses in children 0 to 7 years of age in the Netherlands. Serum samples were collected during a cross-sectional population-based study in 2006 and 2007 and were tested for the presence of antibodies against influenza A/H1N1, A/H3N2, and B viruses representative of viruses present in previous influenza seasons using the hemagglutination inhibition assay. The seroprevalence of antibodies to influenza virus was higher in children 1 to 6 months of age than in children 7 to 12 months of age, which likely reflects the presence of maternally derived antibodies. The proportion of study subjects >1 year of age with detectable antibodies against influenza viruses gradually increased with age until they reached the age of 6 years, when they all had antibodies to at least one influenza A virus. These findings may have implications for the development of vaccination strategies aiming at the protection of young children against seasonal and/or pandemic influenza virus infection.

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Several studies have shown that SARS-CoV-2 BA.1 omicron is an immune escape variant. Meanwhile, however, omicron BA.2 and BA.5 became dominant in many countries and replaced BA.1. As both have several mutations compared to BA.1, we analyzed whether BA.2 and BA.5 show further immune escape relative to BA.1. Here, we characterized neutralization profiles against the BA.2 and BA.5 omicron sub-variants in plasma samples from individuals with different history of exposures to infection/vaccination and found that unvaccinated individuals after a single exposure to BA.2 had limited cross-neutralizing antibodies to pre-omicron variants and to BA.1. Consequently, our antigenic map including all Variants of Concern and BA.1, BA.2 and BA.5 omicron sub-variants, showed that all omicron sub-variants are distinct to pre-omicron variants, but that the three omicron variants are also antigenically distinct from each other. The antibody landscapes illustrate that cross-neutralizing antibodies against the current antigenic space, as described in our maps, are generated only after three or more exposures to antigenically close variants but also after two exposures to antigenically distant variants. Here, we describe the antigenic space inhabited by the relevant SARS-CoV-2 variants, the understanding of which will have important implications for further vaccine strain adaptations.