TY - JOUR
T1 - Half- vs full-dose trivalent inactivated influenza vaccine (2004-2005)
T2 - Age, dose, and sex effects on immune responses
AU - Engler, Renata J M
AU - Nelson, Michael R.
AU - Klote, Mary M.
AU - VanRaden, Mark J.
AU - Huang, Chiung Yu
AU - Cox, Nancy J.
AU - Klimov, Alexander
AU - Keitel, Wendy A.
AU - Nichol, Kristin L.
AU - Carr, Warner W.
AU - Treanor, John J.
PY - 2008/12/22
Y1 - 2008/12/22
N2 - Background: Optimal public health strategies for managing influenza vaccine shortages are not yet defined. Our objective was to determine the effects of age, sex, and dose on the immunogenicity of intramuscular trivalent inactivated vaccine (TIV). Methods: Healthy adults aged 18 to 64 years, stratified by age (18-49 and 50-64 years) and sex, were randomized to receive full- or half-dose TIV. Hemagglutination inhibition titers against vaccine antigens were measured before and 21 days after immunization. A primary outcome of noninferiority was defined as a difference of less than 20% in the upper 95% confidence interval (CI) of the proportion of subjects with strain-specific hemagglutination inhibition antibody titers of 1:40 or higher after vaccination. Secondary outcomes included geometric mean titers, after vaccination side effects, and occurrences of influenza-like illnesses. Results: Amongpreviously immunized subjects (N=1114) receiving half- vs full-dose TIV (age, 18-49 years, n=284 [half] and n=274 [full]; and age 50-64 years, n=276 [half] and n=280 [full]), CIs for proportions of subjects with hemagglutination inhibition antibody titers of 1:40 or higher excluded substantial reduction for all antigens in the 18- to 49-year age group and for B/Shanghai/361/2002 (B) and A/Fujian/411/2002 (A/H3N2) in the 50- to 64-year age group. Geometric mean titer in the female 18-to 49-year age group exceeded male responses for all strains: responses to half-dose TIV that were comparable with male full-dose responses for A/New Caledonia/20/99 (A/H1N1) antigen, 25.4 (95% CI, 20.9-30.9) vs 25.6 (95% CI, 21.3-30.9); A/H3N2 antigen, 60.8 (95% CI, 50.8-72.7) vs 44.1 (95% CI, 37.6-51.8); and B antigen, 64.4 (95% CI, 53.9-76.9) vs 60.7 (95% CI, 51.4-71.7) (findings were similar for the 50- to 64-year age group). Some injection site and systemic reactions (myalgias and/or arthralgias [P<.05], headache [P<.001], and impact of fatigue [P<.05]) were significantly lower in men. The relative risk of medical visits and hospitalizations for influenza-like illnesses were similar in the half- and full-dose groups regardless of age. Conclusions: Antibody responses to intramuscular half-dose TIV in healthy, previously immunized adults were not substantially inferior to the full-dose vaccine, particularly for ages 18 to 49 years. Significantly higher geometric mean titer responses in women were identified for all ages, regardless of dose or influenza strain. Half-dose vaccination may be an effective strategy for healthy adults younger than 50 years in the setting of an influenza vaccine shortage. Trial Registration: clinicaltrials.gov Identifier: NCT00283283.
AB - Background: Optimal public health strategies for managing influenza vaccine shortages are not yet defined. Our objective was to determine the effects of age, sex, and dose on the immunogenicity of intramuscular trivalent inactivated vaccine (TIV). Methods: Healthy adults aged 18 to 64 years, stratified by age (18-49 and 50-64 years) and sex, were randomized to receive full- or half-dose TIV. Hemagglutination inhibition titers against vaccine antigens were measured before and 21 days after immunization. A primary outcome of noninferiority was defined as a difference of less than 20% in the upper 95% confidence interval (CI) of the proportion of subjects with strain-specific hemagglutination inhibition antibody titers of 1:40 or higher after vaccination. Secondary outcomes included geometric mean titers, after vaccination side effects, and occurrences of influenza-like illnesses. Results: Amongpreviously immunized subjects (N=1114) receiving half- vs full-dose TIV (age, 18-49 years, n=284 [half] and n=274 [full]; and age 50-64 years, n=276 [half] and n=280 [full]), CIs for proportions of subjects with hemagglutination inhibition antibody titers of 1:40 or higher excluded substantial reduction for all antigens in the 18- to 49-year age group and for B/Shanghai/361/2002 (B) and A/Fujian/411/2002 (A/H3N2) in the 50- to 64-year age group. Geometric mean titer in the female 18-to 49-year age group exceeded male responses for all strains: responses to half-dose TIV that were comparable with male full-dose responses for A/New Caledonia/20/99 (A/H1N1) antigen, 25.4 (95% CI, 20.9-30.9) vs 25.6 (95% CI, 21.3-30.9); A/H3N2 antigen, 60.8 (95% CI, 50.8-72.7) vs 44.1 (95% CI, 37.6-51.8); and B antigen, 64.4 (95% CI, 53.9-76.9) vs 60.7 (95% CI, 51.4-71.7) (findings were similar for the 50- to 64-year age group). Some injection site and systemic reactions (myalgias and/or arthralgias [P<.05], headache [P<.001], and impact of fatigue [P<.05]) were significantly lower in men. The relative risk of medical visits and hospitalizations for influenza-like illnesses were similar in the half- and full-dose groups regardless of age. Conclusions: Antibody responses to intramuscular half-dose TIV in healthy, previously immunized adults were not substantially inferior to the full-dose vaccine, particularly for ages 18 to 49 years. Significantly higher geometric mean titer responses in women were identified for all ages, regardless of dose or influenza strain. Half-dose vaccination may be an effective strategy for healthy adults younger than 50 years in the setting of an influenza vaccine shortage. Trial Registration: clinicaltrials.gov Identifier: NCT00283283.
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U2 - 10.1001/archinternmed.2008.513
DO - 10.1001/archinternmed.2008.513
M3 - Article
C2 - 19064822
AN - SCOPUS:58149100516
SN - 0003-9926
VL - 168
SP - 2405
EP - 2414
JO - Archives of Internal Medicine
JF - Archives of Internal Medicine
IS - 22
ER -