Safety and immunogenicity of influenza A H1N1 vaccines

The novel swine-origin influenza A H1N1 2009 virus was first identified in April 2009 in Mexico. Since then, it has caused a worldwide pandemic with more than 10,000 deaths documented by December 2009. While many countries adopted pandemic plans and border controls to try to control the spread of the virus, it was quickly realized that the virus was unstoppable. The virus was initially largely susceptible to oseltamivir and zanamivir, and various strategies that included treatment of severe cases, all cases or targeted chemoprophylaxis were used to try to limit the mortality and morbidity due to the virus. However, predictably, resistance to neuraminidase inhibitors has increasingly appeared in different settings and outbreaks of resistant virus have been reported. Mass vaccination is the most economic and effective measure to reduce infection and mortality from influenza. Before this pandemic, several studies were conducted using H5N1 prepandemic vaccines to try to determine the optimal composition and dose of vaccine for a novel strain of influenza. Most of these studies found significantly higher doses required for novel influenza strains and all previous studies showed the need for two doses of vaccine to achieve protective levels of antibody. Once it became apparent that the pandemic was due to H1N1 2009 instead, efforts were redirected to finding the optimal antigen dose and composition including the use of adjuvant combinations. This unique study conducted in ten centers across the People's Republic of China found that a single-dose, 7.5-mu g, nonadjuvanted, split-virion vaccine was sufficiently immunogenic for adults and adolescents aged 12 years and above to meet regulatory requirements for registration. The vaccine was relatively well tolerated with serious adverse reactions mainly high-grade fever in only 0.6% of vaccine recipients. This large, unique study conducted in a developing country using vaccine manufactured in that developing country shows a high degree of seroprotection and has had a major impact on pandemic vaccination strategies worldwide.