Humoral and cellular immune responses after pandemic and seasonal influenza vaccination in humans

Abstract

Vaccination is the most effective prophylaxis against epidemic and pandemic influenza. Annual seasonal influenza vaccination is recommended for high-risk groups such as younger children <5 years old and occupational workers such as frontline healthcare workers (HCW). In 2009, a novel A/H1N1 influenza virus emerged causing the first pandemic of the 21st century. The AS03-adjuvanted inactivated monovalent A/H1N1 pandemic vaccine was rapidly deployed prior to the peak of pandemic in Bergen. HCW were prioritized for the first round of the vaccination, during the autum of 2009 to maintain the integrity of the healthcare system. The A(H1N1)pdm09 strain was subsequently included in seasonal trivalent inactivated influenza vaccines (TIVs) from 2010/2011 until 2016/2017. The trivalent Live Attenuated Influenza Vaccine (LAIV) was licensed for seasonal use in Europe in 2012 and it is recommended for children 2-17 years old. We conducted two vaccine clinical trials using licensed influenza vaccines. In the first clinical trial we evaluated both the immediate and durable humoral and cellular immune responses in HCW vaccinated with the AS03-adjuvanted pandemic vaccine and subsequent annual seasonal TIVs. In the second clinical trial we investigated in depth the follicular helper T (TFH) cell and antibody responses elicited by LAIV in children and adults. We reported that the pandemic vaccine induced rapid homologous and cross-reactive T cell, B cell and antibody responses against the A(H1N1)pdm09 strain and pre-2009 seasonal influenza A/H1N1 strains. We observed that the baseline A(H1N1)pdm09-specific immune responses significantly increased from 2009 to 2013 and were maintained at high levels after 3–4 repeated vaccinations. Collectively our data from the HCW study provide the immunological evidence for continuing annual influenza vaccination policy in adults. Furthermore, we demonstrated that LAIV induced significant increase in influenza specific systemic and local antibody responses against the three vaccine strains tested as early as day 14 post-vaccination. We also showed that LAIV elicited potent and rapid influenza specific TFH cell responses in children. Our LAIV results provide valuable insights into the immunogenicity of LAIV in different age groups with variable levels of pre-existing immunity.