H1N1 Immune Priming and Egg-Adaptation Affect Antibody Responses After Vaccination

Immune priming with seasonal H1N1 viruses earlier in life and egg-adaptation in vaccines can impact antibody responses following influenza vaccination, according to a study published in The Journal of Infectious Diseases.¹

In 2009, influenza A(H1N1)pdm09 viruses first emerged and caused a pandemic; they continue to circulate as seasonal viruses.¹ An A/California/07/09-like strain (CA/09) was originally chosen as the A(H1N1)pdm09 component of multivalent seasonal vaccines.² In 2013 to 2014, the genetic clade 6B emerged with a featured amino acid substitution from lysine (K) to glutamine (Q) at position 163 (K163Q, H1 numbering) in the hemagglutinin (HA), located in antigenic site Sa.^1,3-5 Since then, 6B viruses have diverged further into 6B.1 and 6B.2 subclades, still bearing K163Q, with the 6B.1 subclade predominating globally since the 2015 to 2016 season.⁶ 

Low influenza vaccine effectiveness was reported during the 2015 to 2016 season; therefore, researchers from the Centers for Disease Control and Prevention (CDC) investigated the immune basis for these low responses to circulating A(H1N1)pdm09 viruses following vaccination.¹ The researchers analyzed pre- and post-vaccination sera from 336 adults who received inactivated influenza vaccines (IIV) containing CA/09-like H1 component from 6 seasons (2010-2011 to 2015-2016) to evaluate the antibody responses to 13 A(H1N1) viruses circulated from 1977 to 2016. They found that individual antibody profiles to A(H1N1) viruses revealed 3 priming patterns: USSR/77-, TW/86- or NC/99-priming. More than 20% of adults had reduced titers to cell-propagated circulating 6B.1 and 6B.2 A(H1N1)pdm09 viruses compared with the A/California/07/2009 vaccine virus X-179A. Significantly reduced antibody reactivity to circulating viruses bearing K163Q was only observed in the USSR/77-primed cohort, whereas significantly lower reactivity caused by egg-adapted Q223R change was detected across all 3 cohorts.

“Our study highlights the need to incorporate human serology in influenza surveillance and vaccine strain selection,” concluded the investigators.¹

References

1. Liu F, Tzeng WP, Horner L, et al; Both immune priming and egg-adaptation in the vaccine influence antibody responses to circulating A(H1N1)pdm09 viruses following influenza vaccination in adults [published online June 21, 2018]. J Infect Dis. doi:10.1093/infdis/jiy376
2. World Health Organization. Recommendations for influenza vaccine composition. www.who.int/influenza/vaccines/vaccinerecommendations1/en/. Accessed July 11, 2018.
3. World Health Organization. Recommended composition of influenza virus vaccines for use in the 2015-2016 northern hemisphere influenza season. Wkly Epidemiol Rec. 2015; 90:97-108.
4. Linderman SL, Chambers BS, Zost SJ, et al. Potential antigenic explanation for atypical H1N1 infections among middle-aged adults during the 2013-2014 influenza season. Proceed Natl Acad SciU S A. 2014;111:15798-803.
5. Xu R, Ekiert DC, Krause JC, Hai R, Crowe JE, Jr., Wilson IA. Structural basis of preexisting immunity to the 2009 H1N1 pandemic influenza virus. Science. 2010;328:357-360.
6. World Health Organization. Recommended composition of influenza virus vaccines for use in the 2016-2017 northern hemi6bsphere influenza season. Wkly Epidemiol Rec. 2016; 91:121-132.