ArticlesSafety and immunogenicity of 2009 pandemic influenza A H1N1 vaccines in China: a multicentre, double-blind, randomised, placebo-controlled trial
Introduction
Since the novel swine-origin influenza A H1N1 virus was identified in Mexico and the USA in April, 2009, it has spread throughout the world, prompting WHO to raise the pandemic alert level to phase 6 on June 11, 2009.1, 2, 3 Vaccination is the most effective measure to control the spread of the virus and to reduce associated morbidity and mortality. Existing evidence shows that the currently used trivalent seasonal influenza vaccines are unlikely to provide protection against the new virus.4 The development of new vaccines is therefore urgent, especially in China, where a sixth of the world's population lives.
Clinical trials of vaccines against the 2009 pandemic H1N1 virus are in progress in China, Australia, the USA, and the European Union (EU). These trials recruited fairly small numbers of participants. Data from the USA,5 the UK,6 Australia,7 and China8 suggest that a segment of the population has pre-existing immunity to the pandemic virus, either as a result of past infections or cross-reaction. Therefore, in clinical trials of vaccines for this pandemic, a placebo group is necessary to distinguish between natural and acquired immunity.
We undertook a multicentre, double-blind, randomised, placebo-controlled trial to assess the safety and immunogenicity of eight formulations of 2009 pandemic influenza A H1N1 vaccine produced by ten Chinese manufacturers.
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Participants
This multicentre trial was undertaken between July 22, and Sept 18, 2009, in ten centres in China: Beijing, Wuzhou, and Lipu (Guangxi Autonomous Region); Taizhou and Taixing (Jiangsu Province); Changge and Changshe (Henan Province); Chifeng (Inner Mongolia Autonomous Region); Hengdong (Hunan Province); and Hengshui (Hebei Province). Healthy people aged 3 years or older were recruited for the study. Exclusion criteria included fever (axillary temperature >37·0°C); previous infection with 2009
Results
12 691 participants were enrolled in the ten centres (figure 1 and table 1), including 2828 children (aged 3 to <12 years), 2887 adolescents (12 to <18 years), 4710 adults (18–60 years), and 2266 older adults (61–87 years). 596 (4·7%) participants dropped out during the study period (figure 1).
12 691 participants received the first dose on day 0, and 12 348 participants received the second dose on day 21. These participants completed the 3-day safety observation and were included in the safety
Discussion
Our study showed that all formulations of the 2009 pandemic H1N1 vaccine produced by ten Chinese manufacturers were safe and immunogenic. In adolescents (12 to <18 years), adults (18–60 years), and older adults (>60 years), one dose of the non-adjuvant split-virion vaccine containing 7·5 μg haemagglutinin induced nearly the same level of immune response as did formulations containing more antigen. This formulation required the lowest amount of antigen, which is important during a pandemic when
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