Safety and immunogenicity of revaccination with reduced dose intradermal and standard dose intramuscular influenza vaccines in adults 18-64 years of age.
BACKGROUND
This clinical trial examined the safety and immunogenicity of annual revaccination with Fluzone(®) Intradermal (Sanofi Pasteur, Swiftwater, PA) vaccine compared to a standard intramuscular (IM) split-virion trivalent influenza vaccine (Fluzone(®), Sanofi Pasteur).


METHODS
This phase II, active-controlled, multi-centre, open-label trial was conducted in 2009 and 2010, and enrolled 1250 adults 18-64 years of age who were randomly selected from participants in a phase III influenza vaccine trial the previous year (NCT00772109). Subjects who had previously received the ID vaccine were randomized 2:1 to be revaccinated with the ID or IM vaccine and those who previously received the IM vaccine were randomized 1:1. Solicited reactions were recorded on the day of vaccination and continuing for the next 7 days, non-serious adverse events for 28 days, and serious adverse events for 6 months after vaccination. Hemagglutination inhibition antibody titres were assessed pre-vaccination and at day 28.


RESULTS
Reactions were well-tolerated and resolved in the first 7 days, but erythema, induration, swelling, pruritus and ecchymosis were reported by more subjects receiving the ID vaccine than the IM vaccine. Compared to receipt of IM vaccine in the previous year, ID vaccine in the previous year led to statistically higher rates of erythema, swelling and induration after IM vaccine in the second year. Injection-site pain and systemic reactions did not differ between ID and IM vaccines. No treatment-related serious adverse events were reported. Geometric mean antibody titres, seroprotection rates, and seroconversion rates were non-inferior for the ID and IM vaccines for all three viral strains.


CONCLUSIONS
The ID vaccine was as immunogenic as the IM vaccine, and raised no safety concerns. It can be used interchangeably with the IM vaccine for annual revaccination in adults 18-64 years of age in consecutive years without safety concerns.
Division of Infectious Diseases, Allergy and Immunology, Saint Louis University School of Medicine, 1100 S. Grand Boulevard, St. Louis, MO 63104, USA. Electronic address: gorsegj@slu.edu.
Geoffrey J
GJ
Gorse
Ann R
AR
Falsey
Carol M
CM
Johnson
Dennis
D
Morrison
David L
DL
Fried
John E
JE
Ervin
David P
DP
Greenberg
Ayca
A
Ozol-Godfrey
Victoria
V
Landolfi
Peter H
PH
Tsang
D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007117:Immunization, Secondary / Q000009:adverse effects* / Q000379:methods*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D007271:Injections, Intradermal; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D055815:Young Adult
D000914:Antibodies, Viral; D007252:Influenza Vaccines
AE; CI; GMT; HAI; ID; IM; Immunogenicity; Intradermal; Intramuscular; LLOQ; SAE; Safety; Trivalent influenza vaccine; adverse event; confidence interval; geometric mean titre; hemagglutination inhibition; intradermal; intramuscular; lower limit of quantitation; serious adverse event