Vaccination is of crucial importance in preventing infection and protecting the vulnerable elderly population from disease but, over the past decade, a large number of studies have shown that antibody responses after vaccination are lower in elderly persons than in young adults, and that a variety of vaccines are less efficient in elderly persons [27
Although the relationship between specific anti-influenza virus antibody levels and clinical protection is intrinsically variable [28
], with other factors contributing to protection, such as antibodies to neuraminidase [29
] and cellular immunity [30
], antibody titers against hemaglutinin and derived surrogate end-points are currently considered the basis for licensure of influenza vaccines in the different age groups.
The use of an adjuvant to enhance the antibody response has been considered for a long time to be a valid option to increase the efficacy of influenza vaccines [31
]. Preclinical studies have shown that the adjuvant MF59 is internalized by dendritic cells at the site of injection and facilitates internalization of the antigen to enhance the immune response and produce more antibodies.
This study was performed to evaluate the immunogenicity, using a validated HI assay, of three different inactivated influenza vaccines against both homologous and heterologous influenza strains in all evaluable sera from an original trial in nursing elderly residents with chronic underlying diseases. The original study population mainly comprised very elderly individuals, most of them with at least one underlying medical condition.
Although the sera were retested approximately 10 years after the original study, the data clearly confirmed the previous published evaluations vs. homologous antigens, showing higher immunogenicity in the adjuvanted vaccine group and the lower immune responses in the virosomal group [6
]. After correction according to pre-vaccination status, a statistically significant difference in HI titers was evident in favor of MF59-adjuvanted vaccine against all three vaccine strains, when compared with the split vaccine, and against A/H3N2 and B antigens when compared with the split vaccine. Although all three inactivated vaccines induced very high seroprotection rates, 4-fold increase in titers was consistently higher in the MF59-adjuvanted vaccine group.
In addition, the MF59-adjuvanted influenza vaccine induced a higher level of immunogenicity against strains that bear no close antigenic similarity to those included in the vaccine formulation. For both heterologous A influenza strains, Sub/MF59 induced significantly higher HI antibodies and 4-fold increases in titers than the two non-adjuvanted comparators. For the B drifted strain, significantly higher HI titers were induced by MF59 adjuvanted vaccine, compared with SVV, and both adjuvanted and conventional split vaccine showed the highest increases in titers, compared with the virosomal vaccine.
Multivariate analysis also revealed that the presence of previous vaccination and the type of vaccine used were strong predictors of immune response against heterologous influenza strains ().
All vaccines fulfilled all three CHMP criteria for elderly against homologous strains. Against A heterologous antigens, only Sub/MF59 fulfilled all CHMP criteria versus A/H3N2 and A/H1N1 strains, SVV met all criteria against A/H1N1 and none of them for A/H3N2, Split vaccine fulfilled only one criterion against both antigens. Against B drifted strain only one criterion was met (seroprotection rate) by all vaccines tested.
In conclusion, data from these immunogenicity analyses confirmed that MF59-adjuvanted influenza vaccine can offer greater and broader immunogenicity against influenza in elderly and very elderly individuals who are at high risk of influenza-related complications.
Studies to further evaluate the relationship between vaccines-induced immunogenicity against homologous and heterologous strains and clinical protection are clearly warranted.