Direct comparison of an inactivated subvirion influenza A virus subtype H5N1 vaccine administered by the intradermal and intramuscular routes

Abstract

Background: Direct comparisons of similar doses of a novel influenza virus antigen administered by the intradermal route and the intramuscular route have not been reported.

Methods: A total of 227 healthy adults aged 18-49 years were randomized to receive 2 doses 1 month apart of a subvirion inactivated influenza A virus subtype H5N1 (rgA/Vietnam/1203/2004) vaccine containing 38.7 μg of H5N1 hemagglutinin (HA), by the intramuscular route or by the intradermal route using the Mantoux technique. Clinical and serologic responses were assessed.

Results: Injection site reactions were more frequent in the intradermal group. Immune responses and the geometric mean titer of serum hemagglutination inhibition and neutralizing antibodies 1 month after receipt of the first dose were similar and low but were significantly higher after 2 doses of vaccine in both groups.

Conclusions: Intramuscular and intradermal delivery of vaccine were both well tolerated. Immune responses after 2 doses of this influenza A/H5N1 HA (38.7 μg) were low and not significantly different when given by the intradermal or intramuscular route. Evaluation of higher dosages, alternative intradermal delivery methods, and the addition of adjuvants will be needed to enhance the immunogenicity of inactivated influenza A/H5N1 vaccines by the intradermal route.

Clinical trials registration: NCT00439335.

Figures

Figure 1.

Maximum injection site reactogenicity among 114 subjects in the intramuscular group and 113 subjects in the intradermal group after dose 1. Numbers above the bars represent the proportion of subjects who reported the local reaction during the 7 days after dose 1. Data represent the maximum severity of local site reactogenicity during the 7 days. For injection site pain (discomfort of area at rest), tenderness (discomfort with palpation or movement of the arm), itching, and induration, yellow denotes mild (did not interfere with activity), orange denotes moderate (some interference with daily activities), and red denotes severe (incapacitating). For local induration, erythema, and pigmentation (diameter), yellow denotes mild (50 mm).

Figure 2.

Maximum injection site reactogenicity among 113 subjects in the intramuscular group and 113 subjects in the intradermal group after dose 2. Numbers above the bars represent the proportion of subjects who reported the local reaction during the 7 days after dose 2. Data represent the maximum severity of local site reactogenicity during the 7 days. For local pain, tenderness, itching, and induration, yellow denotes mild (did not interfere with activity), orange denotes moderate (some interference with daily activities), and red denotes severe (incapacitating). For local induration, erythema, and pigmentation (diameter), yellow denotes mild (50 mm).

Figure 3.

Maximum diameter of erythema at the injection site among subjects in the intradermal and intramuscular groups 0–7 days after doses 1 and 2. In the box plots, the center horizontal line is drawn at the 50th percentile (median); the bottom and top edges of the box are located at the 25th and 75th percentiles, respectively; the mean value is denoted by the diamond; the vertical lines extend from the box to the 5th and 95th percentiles; and extreme values are marked with a plot symbol.