Adjuvant Systems: Maximizing Vaccine Potential

Adjuvant systems are designed to enhance vaccine-induced protection by providing a strong and sustained immune response. They can facilitate the development of novel vaccines for challenging diseases which formerly were out of reach. Moreover, they can offer individuals broader protection against multitype pathogens. In some instances, adjuvant systems may even make it possible to reduce the amount of antigen needed and hence to increase vaccine manufacturing capacity, which may be necessary in a public health emergency such as an influenza pandemic. Several clinical studies have confirmed that the use of adjuvant system technology offers the capacity to develop potent vaccines that can address currently unmet medical needs.^2–3

More than two-thirds of GSK Biologicals' vaccines currently under development combine highly immunogenic antigens and uniquely tailored adjuvant systems. This article describes two examples of the use of these adjuvant systems in licensed vaccines and one example of the concept applied in immunotherapy. The first example discusses the role of the adjuvant system AS03 in a prepandemic and pandemic vaccine formulation to achieve antigen-sparing and cross-reactive immunity. The second addresses the challenges in developing a vaccine against human papillomavirus (HPV) to obtain the best possible protection against cervical cancer and the role of the adjuvant system AS04. The third section covers the extension of the boundaries of rational vaccine design with adjuvant system technology to go beyond prevention into cancer treatment with antigen-specific cancer immunotherapeutics (ASCI)

The current H1N1 influenza pandemic displays the expected threat linked to the emergence of a new strain. The global population is largely naïve towards the pandemic strain. In fact, the World Health Organization (WHO) Strategic Advisory Group of Experts (SAGE) on influenza A (H1N1) vaccines advises, in its recommendation of May 19, 2009, that two doses of vaccine may be needed to protect an individual from infection and severe illness.⁴ The Centers for Disease Control and Prevention (CDC) has recently published the results of tests evaluating the cross-reactive immunity potential of seasonal vaccines against the new H1N1 strain and the data suggest that recent (from 2005 to 2009) seasonal influenza vaccines are unlikely to elicit a protective antibody response to the novel influenza A (H1N1) virus.⁵ Another possible concern for a pandemic strain that may be applicable to the current pandemic virus is its ability to mutate rapidly, particularly because it has the potential to infect humans and animal species at the same time. Also, the current H1N1 strain may be subject to antigenic drifting, and that creates the challenge of designing a vaccine that can provide cross-immune response against drifted strains.

Additional concerns in influenza vaccine development are poor pandemic virus yield that may reduce or delay the production of necessary doses and insufficient immunogenicity of the non-adjuvanted inactivated split or subunit pandemic vaccine that may result in the need for a higher antigen dosage.

A vaccine that addresses production yield issues and capacity shortfalls by antigen dose-sparing and can induce broad immunity against drifted strains will be instrumental to protect the human population from a new pandemic influenza strain.⁶

Adjuvantation in Pandemic Vaccines: Experience with H5N1

The H5N1 strain has been the first strong candidate to start a new influenza pandemic. It has presented some of the challenges that a new strain can pose, such as poor immunogenicity of the haemagglutinin (HA) antigen and rapid antigenic drift.^7–8

To address the above challenges, the H5N1 vaccine (Prepandrix) was formulated with AS03, a combination of an oil-in-water-emulsion with an immunoenhancer, a-tocopherol (vitamin E).⁶

The accumulated experience during development of the H5N1 pandemic vaccine candidate will be very useful for the preparation of a pandemic vaccine against the new H1N1 virus.