Immunity following influenza disease and administration of influenza vaccines
For infants the first encounter with influenza viruses commonly occurs in their first or second winter season. Subsequently, each individual acquires a number of influenza infections throughout life. It is expected that up to ~15% of a European population in a temperate climate is infected with influenza in any winter season with higher percentages in children and lower in older people (6).
Whether individuals fall ill when they are infected, is dependent on a number of factors. These include previous exposure to a similar influenza virus that has induced a complete or partial protective immunity to the now circulating virus or, exposure through vaccination with an updated matching influenza vaccine strain.
Commonly, the youngest children and older adult individuals are most affected by severe seasonal influenza infections each year. Paradoxically older adults are less likely to be infected than children but, when they are infected, these older adults are more likely to suffer from severe disease.
Until the 2014/2015 influenza season the immune responses to updated seasonal influenza vaccine were evaluated each year through serological tests in a limited number of healthy individuals (n=~200) according to set criteria established by the European Medicines Agency Committee for Medicinal Products for Human Use (EMA CHMP) committee in 1997. Those immunogenicity criteria were:
For adults 18-59 years of age:
- Seroprotection rate should be >70% - defined as the proportion of vaccinated individuals achieving a haemagglutination-inhibition (HAI) titre of > 1:40
- Seroconversion rate should be > 40% (seroconversion corresponds to negative prevaccination serum converting to a HAI titer >1:40 OR a significant increase in HAI antibody titre, i.e. at least a four-fold titre increase)
For older adults >65 years of age:
- Seroprotection rate should be >60% - defined as the proportion of vaccinated individuals achieving a HAI titre of > 1:40
- Seroconversion rate should be > 30% (seroconversion corresponds to negative prevaccination serum converting to an HAI titer >1:40 OR a significant increase in HAI antibody titre, i.e. at least a four-fold titre increase)
No similar criteria exist for children. These criteria could not be used for the intranasal live attenuated vaccines since mucosal vaccines elicit more mucosal and less systemic immune response.
These criteria were replaced in the EU by Guidelines on product-specific effectiveness observational studies following adoption by EMA CHMP in 2016 which came into effect in February, 2017. In addition, new safety requirements presented in Interim guidance on enhanced safety surveillance for seasonal influenza vaccines came into effect in the EU in 2014. Immune response criteria are retained for the authorisation of new seasonal, pandemic and zoonotic vaccines.