Influenza Vaccination with 1/10th the Full Dose
http://www.100md.com
《新英格兰医药杂志》
To the Editor: As a result of the recent problems in the production of influenza vaccine, there is concern about whether the demand for vaccine will outstrip the supply for the upcoming influenza season.1 An ample vaccine supply is an ever-present concern, given the potential for future influenza pandemics and avian influenza.2 We recently evaluated 1/10th-dose influenza vaccine (Fluarix) as part of a larger phase 1b, randomized, controlled, double-blind vaccine study.3 Healthy volunteers (age range, 18 to 40 years) with negative results on screening tests of hemagglutination inhibition (HAI) for A/Beijing/262/95 and B/Harbin/7/94 were enrolled after they had given written informed consent. A single, intramuscular 1/10th dose of the vaccine (1.5 μg of each hemagglutinin antigen: A/Beijing/262/95, A/Sydney/5/97, and B/Harbin/7/94) was administered in 15 subjects. A second cohort of 14 subjects received the full dose of the vaccine (15 μg of each hemagglutinin antigen). The reduced dose was diluted with phosphate-buffered saline so that the volume was the same as that of the full dose (0.5 ml).
In all the reduced-dose recipients, HAI titers of 1:40 or higher for each antigen developed over the 56-day period of evaluation. This response is considered to provide protection in healthy adults. The mean titers for each antigen were similar in the reduced-dose and full-dose groups on days 14, 28, and 56 (Table 1). On day 56, there was more than a twofold increase in anti-hemagglutinin antibody titers for total IgG, IgG1, and IgG3 A/Sydney/5/97 in the reduced-dose recipients. A 14-fold increase and a 16-fold increase, respectively, in total IgG and IgG1 A/Beijing/262/95 anti-hemagglutinin antibody titers and a 6-fold increase and a 14-fold increase, respectively, in total IgG and IgG1 B/Harbin/7/94 anti-hemagglutinin antibody titers were noted with the 1/10th dose. These were similar to the titers in the subjects who received the full dose.
Table 1. Mean Hemagglutination-Inhibition (HAI) Titers at Baseline and on Days 14, 28, and 56 in the Reduced-Dose and Full-Dose Groups.
Strong type 1 helper T-cell, influenza-specific, cell-mediated immunity may be necessary for optimal protection against influenza infection.4,5 Ex vivo restimulation of peripheral-blood mononuclear cells with the three influenza hemagglutinin antigens (0.5 μg per milliliter) was evaluated at baseline, on day 14, and on day 28. T-cell proliferation increased from baseline (range of increase, twofold to eightfold) in recipients of the reduced dose for each antigen, and the increase was similar to that in recipients of the full dose.
In the event of a serious influenza pandemic, mass vaccination may be required, targeting more than ill or elderly persons, who are at highest risk for serious disease, in order to increase general or "herd" immunity and to reduce the overall number of infections and the rate of subsequent transmission. The observation that 1/10th-dose vaccine appears to result in protective titers (i.e., 1:40) in healthy adults as frequently as full-dose vaccine (lower limit of the 95 percent confidence interval, 93 percent) is valuable. Once confirmatory studies of immunogenicity and protection have been conducted, this approach may permit a 10-fold increase in available vaccine for healthy young adults, if needed in times of a shortage in the vaccine supply.
Curtis L. Cooper, M.D.
University of Ottawa
Ottawa, ON K1H 8L6, Canada
Heather Davis, Ph.D.
Coley Pharmaceutical Group
Ottawa, ON K2K 3A2, Canada
D.W. Cameron, M.D.
University of Ottawa
Ottawa, ON K1H 8L6, Canada
References
Interim influenza vaccination recommendations, 2004–05 influenza season. MMWR Dispatch 2004;53:1.
Update: influenza activity -- United States and worldwide, 2003-04 season, and composition of the 2004-05 influenza vaccine. MMWR Morb Mortal Wkly Rep 2004;53:547-552.
Cooper CL, Davis HL, Morris ML, et al. Safety and immunogenicity of CPG 7909 injection as an adjuvant to Fluarix influenza vaccine. Vaccine 2004;22:3136-3143.
McMichael AJ, Gotch FM, Noble GR, Beare PA. Cytotoxic T-cell immunity to influenza. N Engl J Med 1983;309:13-17.
Deng Y, Jing Y, Campbell AE, Gravenstein S. Age-related impaired type 1 T cell responses to influenza: reduced activation ex vivo, decreased expansion in CTL culture in vitro, and blunted response to influenza vaccination in vivo in the elderly. J Immunol 2004;172:3437-3446.
In all the reduced-dose recipients, HAI titers of 1:40 or higher for each antigen developed over the 56-day period of evaluation. This response is considered to provide protection in healthy adults. The mean titers for each antigen were similar in the reduced-dose and full-dose groups on days 14, 28, and 56 (Table 1). On day 56, there was more than a twofold increase in anti-hemagglutinin antibody titers for total IgG, IgG1, and IgG3 A/Sydney/5/97 in the reduced-dose recipients. A 14-fold increase and a 16-fold increase, respectively, in total IgG and IgG1 A/Beijing/262/95 anti-hemagglutinin antibody titers and a 6-fold increase and a 14-fold increase, respectively, in total IgG and IgG1 B/Harbin/7/94 anti-hemagglutinin antibody titers were noted with the 1/10th dose. These were similar to the titers in the subjects who received the full dose.
Table 1. Mean Hemagglutination-Inhibition (HAI) Titers at Baseline and on Days 14, 28, and 56 in the Reduced-Dose and Full-Dose Groups.
Strong type 1 helper T-cell, influenza-specific, cell-mediated immunity may be necessary for optimal protection against influenza infection.4,5 Ex vivo restimulation of peripheral-blood mononuclear cells with the three influenza hemagglutinin antigens (0.5 μg per milliliter) was evaluated at baseline, on day 14, and on day 28. T-cell proliferation increased from baseline (range of increase, twofold to eightfold) in recipients of the reduced dose for each antigen, and the increase was similar to that in recipients of the full dose.
In the event of a serious influenza pandemic, mass vaccination may be required, targeting more than ill or elderly persons, who are at highest risk for serious disease, in order to increase general or "herd" immunity and to reduce the overall number of infections and the rate of subsequent transmission. The observation that 1/10th-dose vaccine appears to result in protective titers (i.e., 1:40) in healthy adults as frequently as full-dose vaccine (lower limit of the 95 percent confidence interval, 93 percent) is valuable. Once confirmatory studies of immunogenicity and protection have been conducted, this approach may permit a 10-fold increase in available vaccine for healthy young adults, if needed in times of a shortage in the vaccine supply.
Curtis L. Cooper, M.D.
University of Ottawa
Ottawa, ON K1H 8L6, Canada
Heather Davis, Ph.D.
Coley Pharmaceutical Group
Ottawa, ON K2K 3A2, Canada
D.W. Cameron, M.D.
University of Ottawa
Ottawa, ON K1H 8L6, Canada
References
Interim influenza vaccination recommendations, 2004–05 influenza season. MMWR Dispatch 2004;53:1.
Update: influenza activity -- United States and worldwide, 2003-04 season, and composition of the 2004-05 influenza vaccine. MMWR Morb Mortal Wkly Rep 2004;53:547-552.
Cooper CL, Davis HL, Morris ML, et al. Safety and immunogenicity of CPG 7909 injection as an adjuvant to Fluarix influenza vaccine. Vaccine 2004;22:3136-3143.
McMichael AJ, Gotch FM, Noble GR, Beare PA. Cytotoxic T-cell immunity to influenza. N Engl J Med 1983;309:13-17.
Deng Y, Jing Y, Campbell AE, Gravenstein S. Age-related impaired type 1 T cell responses to influenza: reduced activation ex vivo, decreased expansion in CTL culture in vitro, and blunted response to influenza vaccination in vivo in the elderly. J Immunol 2004;172:3437-3446.