Immunodominance hierarchy after seasonal influenza vaccination

ABSTRACT

Current influenza vaccines elicit humoral immune responses against the haemagglutinin (HA) protein of influenza viruses. Different antigenic sites have been identified in the HA head as the main target of haemagglutination inhibition (HAI) antibodies (Sb, Sa, Cb, Ca1 and Ca2). To determine immunodominance (ID) of each site, we performed HAI assays against a panel of mutant viruses, each one lacking one of the classically defined antigenic sites and compared it to wild type (Wt). Agglutinating antibodies were measured before and after vaccination in two different regimens: Quadrivalent Influenza Vaccine (QIV) in young adults; or Adjuvanted Trivalent influenza Vaccine (ATIV) in elderly. Our results showed abs before vaccination were significantly reduced against all antigenic sites in the elderly and only against Sb and Ca2 in young adults compared to the Wt. Humoral response to vaccination was significantly reduced against all viruses compared to the Wt for the ATIV and only against Sb and Ca2 for the QIV. The strongest reduction was observed in all cases against Sb followed by Ca2. We concluded that ID profile was clearly dominated by Sb followed by Ca2. Additionally, the antibody response evolved with age, increasing the response towards less immunodominant epitopes of HA head. Adjuvants can positively influence ID hierarchy broadening responses towards multiple antigenic sites of HA head.

KEYWORDS:

• Immunodominance
• hemagglutinin
• influenza
• vaccines
• adjuvants

Acknowledgements

We thank Richard Cadagan for technical assistance. We also thank Dr Peter Palese and Dr Sean Liu for providing the recombinant viruses used in this study. This work was supported by “Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica”, SEIMC mobility grant awarded to LSdP. LSdP received a Río Hortega grant (CM20/00138) from Instituto de Salud Carlos III (Co-funded by European Regional Development Fund/European Social Fund “A way to make Europe”/“Investing in your future”). This work was also partly supported by CRIPT (Center for Research on Influenza Pathogenesis and Transmission), a National Institute of Allergy and Infectious Diseases (NIAID) funded Center of Excellence for Influenza Research and Response (CEIRR, contract 75N93021C00014), by Collaborative Influenza Vaccine Innovation Centers CIVIC (NIAID contract 75N93019C000510) and by NIAID grants P01AI097092, R01AI142086, U01AI165452 and U19AI168631 to AG-S.

Disclosure statement

The A.G.-S. laboratory has received research support from Pfizer, Senhwa Biosciences, Kenall Manufacturing, Avimex, Johnson & Johnson, Dynavax, 7Hills Pharma, Pharmamar, ImmunityBio, Accurius, Nanocomposix, Hexamer, N-fold LLC, Model Medicines, Atea Pharma, Applied Biological Laboratories and Merck, outside of the reported work. A.G.-S. has consulting agreements for the following companies involving cash and/or stock: Vivaldi Biosciences, Contrafect, 7Hills Pharma, Avimex, Vaxalto, Pagoda, Accurius, Esperovax, Farmak, Applied Biological Laboratories, Pharmamar, Paratus, CureLab Oncology, CureLab Veterinary, Synairgen and Pfizer, outside of the reported work. A.G.-S. has been an invited speaker in meeting events organized by Seqirus, Janssen and Astrazeneca. A.G.-S. is inventor on patents and patent applications on the use of antivirals and vaccines for the treatment and prevention of virus infections and cancer, owned by the Icahn School of Medicine at Mount Sinai, New York, outside of the reported work.

Data availability statement

The data that support the findings of this study are available from the corresponding authors, T.A. and A.G-S. upon reasonable request.

Additional information

Funding

This work was supported by Instituto de Salud Carlos III [grant number CM20/00138]; National Institute of Allergy and Infectious Diseases [grant number P01AI097092, R01AI142086, U01AI165452,U19AI168631]; Center of Excellence for Influenza Research and Response [grant number 75N93021C00014]; Collaborative Influenza Vaccine Innovation Centers [grant number 75N93019C000510]; Center for Research on Influenza Pathogenesis and Transmission.