Clinical Trials Pave the Way for Single-dose Flu Immunization

At Monday’s meeting of vaccinologists attending the 12th Annual World Vaccine Conference in Lyon, France, Martine Denis, Senior Director Clinical Development, Influenza Vaccines, Sanofi Pasteur, reported that immune response has been achieved after a single vaccination against 2009 influenza A H1N1 in two clinical trials in the USA.

The trials, started in August 2009, were designed to find the appropriate antigen dose and vaccination schedule for the 2009 pandemic influenza A H1N1. The main objectives were to assess the immunogenicity and safety of the candidate vaccines (monovalent split inactivated vaccine manufactured in eggs, A/California/7/2009 strain) after each injection).

Denis told the delegates that the outcome was “a major finding was quite unexpected: the ability to induce antibodies after one dose of a licensed monovalent pandemic H1N1 vaccine.” He also said that “one dose of vaccine was highly immunogenic in adults, suggesting that it afforded sufficient protection against this pandemic influenza A H1N1 virus. Two doses of vaccine will probably be needed in children younger than nine years.”

Healthy children and adults were randomly assigned to H1N1 vaccine containing per dose 7•5 μg (children and adults), 15 μg (children and adults), or 30 μg (adults only) haemagglutinin in the two placebo-controlled, observer-masked, multicentre phase II studies. Primary outcome was haemagglutination inhibition antibody response 21 days after the first of two planned vaccinations.

No vaccine-related serious adverse events occurred. Injection-site and systemic reactions were reported by up to nearly 50% of every age and vaccine group, with no noticeable differences between vaccine and placebo groups. Safety and reactogenicity of the vaccine were acceptable and similar to those of seasonal vaccine.

In Europe, there was parallel development of adjuvanted (Humenza) and non adjuvanted (Panenza) vaccines. Panenza was first registered in France through the decentralized procedure, followed by approvals in other countries. Positive opinion on Humenza was obtained in February 2010. Clinical trials started in August 2009 and initial study results were reported in adult trials in October 2009.

High antibody responses were induced by either the adjuvanted or non-adjuvanted vaccine in adults (EU) 21 days after post-vaccination for doses 3.8mcg HA AF03 (emulsion-based adjuvant), 7.5mcg HA AF03 and 15mcg HA. High antibody responses were induced by either adjuvanted or non-adjuvanted vaccine in children (EU) with two injections of the AF03-adjuvanted or non-adjuvanted A(H1N1) vaccines. All children developed protective titers of HAI antibodies.

Denis said that, despite timeline optimization during a pandemic, clinical data are often made available too late to guide decision-making at the public health level. In post- approval activities, effectiveness and safety of A/H1N1 pandemic vaccines were assessed in the US and Europe. He said that data available thus far suggest similar level of effectiveness compared to seasonal vaccine. Large-scale safety monitoring was organized by government agencies as well as Sanofi Pasteur. Denis said that researchers found no evidence of increased risk of Guillain-Barre syndrome after pandemic vaccination.