title: Influenza vaccines: the effect of vaccine dose on antibody response in primed populations during the ongoing interpandemic period. A review of the literature.
abstract: Health authorities tend to favour an increase of the antigen dose in inactivated influenza vaccines from < or = 10 micrograms haemagglutinin (HA) per vaccine strain to 15 micrograms HA/strain. The increased dose is expected to yield a meaningful increase in the number of subjects to be protected after vaccination. To verify this expectation, we have reviewed 20 published reports (1978-1991) of serological studies in which anti-HA-IgG antibody after different doses was measured. In the review, stratification groups of previously primed subjects were formed and the antibody response was estimated for doses of 10 and 15 micrograms HA by linear k*2-chi 2 model. Despite a considerable heterogenicity of study populations, study designs, vaccine types and strains, and antibody assays, the results were consistent in revealing high protection rates (> or = 75%) for a 10 micrograms HA dose of influenza A vaccine components. For both response and protection rates, an increase of the antigenic load from 10 to 15 micrograms HA was not associated with a meaningful increase of seroresponse: in 38 out of 39 stratification groups, the increase of response and/or protection rate varied between -9% and +8%, with a median of 1.5%. These results do not justify the expectation that a vaccine dose of 15 micrograms HA per strain would be clinically superior to a dose of 10 micrograms HA. Only in a group of immune-compromised patients on chronic intermittent haemodialysis were results in favour of a higher dose found, which may justify further evaluation in this special population.
authors.affiliation: Department of Virology, Erasmus University Rotterdam, The Netherlands.
authors.forename: A M
authors.initials: AM
authors.lastname: Palache
authors.forename: W E
authors.initials: WE
authors.lastname: Beyer
authors.forename: G
authors.initials: G
authors.lastname: Lüchters
authors.forename: R
authors.initials: R
authors.lastname: Völker
authors.forename: M J
authors.initials: MJ
authors.lastname: Sprenger
authors.forename: N
authors.initials: N
authors.lastname: Masurel
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000914:Antibodies, Viral / Q000096:biosynthesis*; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic / Q000379:methods; D004196:Disease Outbreaks; D004306:Dose-Response Relationship, Immunologic; D005069:Evaluation Studies as Topic; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000008:administration & dosage / Q000276:immunology*; D006801:Humans; D007110:Immunity, Active; D016867:Immunocompromised Host; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology; D007251:Influenza, Human / Q000453:epidemiology / Q000517:prevention & control; D008875:Middle Aged; D009975:Orthomyxoviridae / Q000276:immunology*; D012107:Research Design; D014611:Vaccination / Q000379:methods; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated