Priming with AS03A -adjuvanted H5N1 influenza vaccine improves the kinetics, magnitude and durability of the immune response after a heterologous booster vaccination: An open non-randomised extension of a double-blind randomised primary study

• Published in: Vaccine Vol. 28; no. 3; pp. 849 - 857
• Main Authors: Leroux-Roels, Isabel, Roman, François, Forgus, Sheron, Maes, Cathy, De Boever, Fien, Dramé, Mamadou, Gillard, Paul, van der Most, Robbert, Van Mechelen, Marcelle, Hanon, Emmanuel, Leroux-Roels, Geert
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier 08.01.2010; Elsevier Limited
• Subjects: Allergy and Immunology; Applied microbiology; Avian flu; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Immune response; Immunogenicity; Medical research; Microbiology; Miscellaneous; Pandemics; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Virology; Pandemic influenza; Vaccine; Adjuvant; Immune response; Booster vaccination; Orthomyxoviridae; Infection; Virus; Influenzavirus A; Influenza A virus; Viral disease; Immunological adjuvant; Influenza; Kinetics
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2009.10.017

Abstract An influenza vaccine with cross-immunogenic potential could play a key role in pandemic mitigation by promoting a rapid immune response to infection and/or subsequent vaccination with strains drifted from the primary vaccine strain. Here we assess the role of AS03A (an oil-in-water emulsion based Adjuvant System containing tocopherol) in this prime-boost concept using H5N1 as a model shift influenza antigen. In this open, non-randomised study ( NCT00506350 ; an extension of an earlier randomised study) we assessed immunogenicity in nine groups of 35–50 volunteers aged 19–61 years following administration of AS03A -adjuvanted split-virion H5N1 vaccine containing 3.75 μg of haemagglutinin (HA) from the A/Indonesia/5/2005(IBCDC-RG2) clade 2.1 strain. A single booster dose of vaccine was administered to four groups primed 14 months previously with different HA levels of AS03A -adjuvanted clade 1 A/Vietnam/1194/2004 H5N1 vaccine. Two booster doses (given 21 days apart) were administered to four groups primed 14 months previously with different HA levels of non-adjuvanted A/Vietnam/1194/2004 H5N1 vaccine and also to a control group of un-primed subjects. In individuals primed 14 months earlier with AS03A -adjuvanted A/Vietnam/1194/2004 vaccines, a single booster dose of AS03A -adjuvanted A/Indonesia/5/2005 induced rapid immune responses (licensure criteria met in 7–14 days) comparable to that observed in the un-primed control group following two doses of adjuvanted vaccine. In contrast, individuals primed with non-adjuvanted formulations exhibited minimal immune responses which, even after two doses, were unexpectedly much lower than that observed in un-primed subjects. AS03A enhances the initial priming effect of pandemic influenza vaccination enabling a rapid humoral response to single dose boosting with a heterologous strain at 14 months. In contrast, priming without adjuvant appears to inhibit the response to subsequent vaccination with a heterologous strain. These findings should guide the development of vaccines to combat the present influenza A/H1N1 pandemic.