Addressing Unmet Medical Needs Through Tailored Vaccine Design: The Importance of Adjuvant Systems - It is now possible to combine antigens with specific adjuvant systems to create more-effective vacc


Addressing Unmet Medical Needs Through Tailored Vaccine Design: The Importance of Adjuvant Systems
It is now possible to combine antigens with specific adjuvant systems to create more-effective vaccines.

BioPharm International Supplements

Clinical Experience with the H5N1/AS03 Formulation

Several clinical studies support the benefits of AS03 for a pandemic influenza vaccine.

The formulation with AS03 showed significant antigen sparing capabilities compared to the non-adjuvanted vaccine. With the AS03-adjuvanted formulation, >80% of subjects who received two (3.75 μg) doses of antigen (as a comparison, seasonal vaccine contains 15 μg of antigen per strain) showed a strong seroprotective immune response, and all the European Committee for Medicinal Products for Human use (CHMP) and US Food and Drug Administration (FDA) criteria for immunogenicity were met.6 At the highest dose (30 μg) the non-adjuvanted formulation met only two out of three CHMP criteria and none of the FDA criteria for immunogenicity.

The same study provided convincing evidence that the AS03-adjuvanted pandemic influenza vaccine induces a high level of cross-reactive immunity to drifted strains of H5N1 in humans.6 These results are in line with cross-protective responses observed in animal models.9 Additional clinical data showed broad cross-clade reactive neutralizing antibody response with AS03, compared with no response in the non-adjuvanted group.10

Preliminary study results obtained with the AS03-adjuvanted H5N1 vaccine in elderly volunteers and in children have also shown a satisfactory immune response against the vaccine strain.11–12

A recent study has shown that administration of the second dose of vaccine from 6 up to 12 months after the first dose induced similar levels of cross-clade immunity, as compared to the standard schedule (two doses, 21 days apart, currently recommended for adults 18–60 years of age in Europe). These data suggest that the timing of second dose administration of the H5N1/AS03 vaccine can be flexible without reducing the robustness of the immune response achieved.13

The safety of the H5N1/AS03-adjuvanted vaccine has been assessed in several clinical studies. The safety data set includes more than 10,000 subjects, mainly enrolled in large studies in Europe and Asia, who received injections of the AS03/H5N1 vaccine formulation.14–15 Across studies, it was observed that the H5N1/AS03-adjuvanted vaccine increased the frequency and intensity of injection site reactions in comparison with non-adjuvanted vaccines. Solicited general adverse events such as headache, fatigue, and myalgia were also more frequently observed with the adjuvanted vaccine. However, these solicited adverse events were mild to moderate in intensity and of short duration. The overall safety profile of the adjuvanted vaccine has been considered clinically acceptable.

Benefits of the H5N1/AS03 Vaccine
In conclusion, the formulation of the H5N1 pandemic influenza vaccine with AS03 results in an effective vaccine with a favorable safety profile. A first crucial benefit is antigen-sparing which allows more people to be vaccinated more rapidly. Other key advantages include high flexibility with regard to second dose vaccine administration and cross-reactive immunity against drifted strains, which is important because that virus mutation is likely to continue during a pandemic (Box 1). These benefits may be explained by a tailored and enhanced interaction of the adjuvant–antigen combination with cells of the innate immune system and consequently a better stimulation of the adaptive immune response compared to the formulation without adjuvant.

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