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

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Investigators find that individual antibody profiles to A(H1N1) viruses revealed three priming patterns.
Investigators find that individual antibody profiles to A(H1N1) viruses revealed three priming patterns.

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.
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