Safety, humoral and cell mediated immune responses to two formulations of an inactivated, split-virion influenza A/H5N1 vaccine in children

Abstract

Background: Highly pathogenic influenza A/H5N1 has caused outbreaks in wild birds and poultry in Asia, Africa and Europe. It has also infected people, especially children, causing severe illness and death. Although the virus shows limited ability to transmit between humans, A/H5N1 represents a potential source of the next influenza pandemic. This study assesses the safety and immunogenicity of aluminium hydroxide adjuvanted (Al) and non adjuvanted influenza A/Vietnam/1194/2004 NIBRG-14 (H5N1) vaccine in children.

Methods and findings: In a Phase II, open, randomised, multicentre trial 180 children aged 6 months to 17 years received two injections, 21 days apart, of vaccine containing either: 30 microg haemagglutinin (HA) with adjuvant (30 microg+Al) or 7.5 microg HA without adjuvant. An additional 60 children aged 6-35 months received two "half dose" injections (ie 15 microg+Al or 3.8 microg). Safety was followed for 21 days after vaccination. Antibody responses were assessed 21 days after each injection and cellular immune responses were explored. Vaccination appeared well tolerated in all age groups. The 30 microg+Al formulation was more immunogenic than 7.5 microg in all age groups: in these two groups 79% and 46% had haemagglutinination inhibition antibody titres > or =32 (1/dil). Among 6-35 month-olds, the full doses were more immunogenic than their half dose equivalents. Vaccination induced a predominantly Th2 response against H5 HA.

Conclusions: This influenza A(H5N1) vaccine was well tolerated and immunogenic in children and infants, with Al adjuvant providing a clear immunogenic advantage. These results demonstrate that an H5N1 Al-adjuvanted vaccine, previously shown to be immunogenic and safe in adults, can also be used in children, the group most at risk for pandemic influenza.

Trial registration: ClinicalTrials.gov NCT00491985.

Conflict of interest statement

Competing Interests: Stephanie Pepin and Nolwenn Nougarede are both employed by the study sponsor, Sanofi Pasteur. All other authors have no competing interests.

Figures

Figure 1. Haemagglutination inhibition antibody response 21 days after two injections, 21 days apart of adjuvanted or non-adjuvanted H5N1 vaccine.

Results are presented per age and vaccine formulation group as geometric mean titres (GMT) and the proportion of subjects with titres ≥32.

Figure 2. Levels of IFNγ and IL5 secreted after in vitro re-stimulation with recombinant H5 haemagglutinin by cells obtained before and eight days after two injections, 21 days apart, of adjuvanted or non-adjuvanted H5N1 vaccine in groups of children aged 6–35 months.

Symbols represent results from individual samples, bars indicate the median level.