Age and prior exposure to the H1 or B influenza virus may affect the cross-reactivity of H3-specific postvaccination responses and influence the efficacy of the seasonal influenza vaccine, according to research published in the Open Forum Infectious Diseases.

A total of 3664 healthy individuals aged ≥3 years were recruited in a study that was conducted in a single city in China. Patients were stratified by age groups: 3 to 17 years, 18 to 59 years, and ≥60 years. Participants were randomly assigned to either 1 dose of the experimental quadrivalent influenza vaccine (QIV), trivalent influenza vaccine (TIV) Victoria, or the TIV Yamagata.

Investigators selected a random 360 paired pre and postvaccination serum samples from 1832 participants who received the QIV. This sample included 120 individuals aged 3 to 17 years, 120 adults aged 18 to 59 years, and 120 elderly people aged ≥60 years. Blood samples were obtained from each participant before and 28 days after vaccination. The samples were then tested by hemagglutination-inhibition tests against vaccine strains and circulating variants present during China’s 2015 and 2016 influenza seasons.

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Higher cross-reactive antibodies titers against A/JiangsuTinghu/11019/2015(H3N2) were observed in individuals with H1-priming compared with those with B-priming (P =.038). Additionally, the investigators observed higher cross-reactive antibodies titers against A/Jiangsu Qinhuai/11059/2015(H3N2) in individuals with H1-priming vs those with both H1 and B priming (P =.036).

In contrast, higher cross-reactive antibodies titers against A/JiangsuQinhuai/11059/2015(H3N2) were observed in individuals with no H1 and B-priming compared with individuals with both H1 and B priming (P =.012). The investigators also calculated antigenic distance using antigenic maps and found the results were well matched with serologic results. This suggested that the farther the antigenic distance, the greater geometric mean titers reduction decreased. Also, children between 3 and 17 years showed the most cross-reactive response to H3N2 and B-Yamagata subtypes.

The study was limited in that it did not monitor influenza incidence rates in patients during the influenza seasons after 2015 and 2016. Similarly, the cross-reactivity of influenza vaccine was evaluated for only 1 season.

According to the researchers, the findings suggest “that a complex preexisting immunity to previous influenza exposure should also be fully considered in the next generation of influenza vaccine design.”


Cao J-Q, Jin P-F, Zeng Z-Z, et al. Effects of prior influenza exposure on immunogenicity of influenza vaccine [published online May 26, 2020]. Open Forum Infect Dis. doi:10.1093/ofid/ofaa181