AS03 is an Adjuvant System composed of α-tocopherol, squalene and polysorbate 80 in an oil-in-water emulsion. In various nonclinical and clinical studies, high levels of antigen-specific antibodies were obtained after administration of an AS03-adjuvanted vaccine, permitting antigen-sparing strategies. AS03 has been shown to enhance the vaccine antigen-specific adaptive response by activating the innate immune system locally and by increasing antigen uptake and presentation in draining lymph nodes, a process that is modulated by the presence of α-tocopherol in AS03. In nonclinical models of the AS03-adjuvanted prepandemic H5N1 influenza vaccine, increased levels of anti-influenza antibody afforded protection against disease and against virus replication of influenza strains homologous and heterologous to the vaccine strain. By incorporating AS03 in the pandemic H1N1/2009 vaccine, vaccine immunogenicity was increased compared with nonadjuvanted H1N1 vaccines. High H1N1/2009/AS03 vaccine effectiveness was demonstrated in several assessments in multiple populations. Altogether, the nonclinical and clinical data illustrate the ability of AS03 to induce superior adaptive responses against the vaccine antigen, principally in terms of antibody levels and immune memory. In general, these results support the concept of Adjuvant Systems as a plausible approach to develop new effective vaccines.

Development and evaluation of AS03, an Adjuvant System containing α-tocopherol and squalene in an oil-in-water emulsion

Safety and immunogenicity of S-Trimer (SCB-2019), a protein subunit vaccine candidate for COVID-19 in healthy adults: a phase 1, randomised, double-blind, placebo-controlled trial.

In spite of current influenza vaccines being immunogenic, evolution of the influenza virus can reduce efficacy and so influenza remains a major threat to public health. One approach to improve infl...

https://www.tandfonline.com/doi/pdf/10.1080/21645515.2017.1415684

Adjuvanted influenza vaccines

17 – Inactivated influenza vaccines

Advax™, a polysaccharide adjuvant derived from delta inulin, provides improved influenza vaccine protection through broad-based enhancement of adaptive immune responses

Background. Highly pathogenic avian influenza H5N1 viruses remain a threat to human health, with potential to become pandemic agents.

Methods. This phase III, placebo-controlled, observer-blinded study evaluated the immunogenicity, cross-reactivity, safety, and lot consistency of 2 doses of oil-in-water (AS03A) adjuvanted H5N1 A/Indonesia/05/2005 (3.75 μg hemagglutinin antigen) prepandemic candidate vaccine in 4561 adults aged 18–91 years.

Results. Humoral antibody responses in the H5N1 vaccine groups fulfilled US and European immunogenicity licensure criteria for pandemic vaccines in all age strata 21 days after the second dose. At 6 months after the administration of the primary dose, serum antibody seroconversion rates continued to fulfill licensure criteria. Neutralizing cross-clade immune responses were demonstrated against clade 1 A/Vietnam/1194/2004. Consistency was demonstrated for 3 consecutive H5N1 vaccine lots. Temporary injection-site pain was more frequent with H5N1 vaccine than placebo (89.3% and 70.7% in the 18–64 and ≥65 years strata vs 22.2% and 14.4% in the placebo groups). Unsolicited adverse event frequency, including medically attended and serious events, was similar between groups through day 364.

Conclusions. In adults and elderly adults, AS03A-adjuvanted H5N1 candidate vaccine was highly immunogenic for A/Indonesia/05/2005, with cross-reactivity against A/Vietnam/1194/2004. Temporary injection site reactions were more frequent with H5N1 vaccine than placebo, although the H5N1 vaccine was well tolerated overall.

Clinical Trials Registration. {"type":"clinical-trial","attrs":{"text":"NCT00616928","term_id":"NCT00616928"}}NCT00616928.

/pdf/dose-sparing-h5n1-a-indonesia-05-2005-pre-pandemic-influenza-225ffifl57.pdf

Marc Shepard

Papers

Dose-Sparing H5N1 A/Indonesia/05/2005 Pre-pandemic Influenza Vaccine in Adults and Elderly Adults: A Phase III, Placebo-Controlled, Randomized Study