Vaccine and Pharmaceutical Formulation and Stabilization Technologies

Enhancing product efficacy

Fueling innovation with adjuvant technologies

Every year vaccinations against infectious diseases save the lives of 2.5 million children and protect over 100 million more from illness and disability.1 However, millions of children remain at risk in developing countries, where the global infectious disease burden is highest,2 because new vaccines that protect against specific health threats are either prohibitively expensive or not yet available. For other vaccine targets, the antigens elicit an insufficient immune response on their own, requiring innovation. Advanced adjuvants that improve vaccine efficacy as well as reduce the cost per dose of vaccine could potentially address these gaps and help to accelerate the development, coverage, and impact of many new vaccines of critical importance to developing countries.

Promising advantages

When properly formulated and matched to the appropriate antigen, adjuvants can help to improve vaccine efficacy by augmenting the breadth and magnitude of the vaccine immune response. A handful of adjuvants are currently licensed for human vaccination, and a number of new adjuvants are helping certain vaccines to reach advanced stages of product development. These adjuvants are addressing previous development barriers by enhancing otherwise poorly immunogenic antigens or biasing the immune response toward the type of response needed to protect against specific pathogens, for example, through humoral, cell-mediated, or mucosal immunity. Some of the adjuvants have also helped to reduce the dose required per person, though broad effects on affordability are still being assessed.

The influence adjuvants can have on the antigen and resulting immune response includes:

  • Enhancing functional antibody titers.
  • Allowing for greater breadth of antibody cross-reactivity.
  • Enabling memory of the initial immune response.
  • Facilitating mucosal homing of immune effector cells through the upregulation of the cells’ homing markers.
  • Overcoming extrinsic constraints related to poor nutrition or immunocompromised influences.
  • Surmounting intrinsic restrictions to improve poorly immunogenic antigens.

The broad impact that adjuvants can have on vaccination includes:

  • Accelerating the onset of the immune response.
  • Potentially reducing the need for a boost.
  • Diminishing the required antigen dose (i.e., facilitating dose sparing).
  • Prolonging the duration of the immune response.

Challenges to uptake and use

Although major developments in antigen discovery over the past decade have accelerated the vaccine development process for a number of new indications, global manufacturers still tend to focus on products needed by wealthy countries to ensure an adequate return on investment. By comparison, many developing-country manufacturers and product development partnerships (PDPs) are pioneering the research and development of vaccines that meet the unique needs of public health programs in low-income countries. However, key hurdles remain in the uptake and use of the latest adjuvant technologies, including:

  • Intellectual property restrictions. Most adjuvant intellectual property is held by a small concentration of pharmaceutical and biotech companies. As a result, many product development efforts do not pursue proprietary adjuvants. Or, if they have succeeded in negotiating access, they must evaluate performance one adjuvant at a time, which can be inefficient, costly, and time-consuming.
  • Limited access to adjuvant-related data. Typically, the opportunity for selecting the most suitable adjuvant is missed because head-to-head comparisons of different adjuvants are not permitted by the adjuvant developers. Without these comparisons, vaccine manufacturers and PDPs do not have the data that are relevant to adjuvant selection and related formulation and evaluation methods.
  • Additional technical concerns. Aluminum salts, also known as alum, are the primary adjuvants used in vaccines worldwide—helping to boost immunogenicity and product efficacy. However, alum-adjuvanted vaccines are also more sensitive to freezing temperatures, which can cause the aluminum salts to agglomerate, permanently compromising vaccine efficacy.

Pathway forward

PATH is working to surmount these hurdles by expanding global access to proprietary and nonproprietary adjuvants as well as relevant adjuvant formulation technologies, better facilitating their exploration and use by developing-country manufacturers, vaccine development programs, and PDPs. Visit our page on PATH’s scope of work in adjuvants to learn more »

Our scientists have also addressed the issue of freeze sensitivity for alum-adjuvanted vaccines through the development of a safe, effective, and low-cost freeze-protection technology. Visit our page on vaccine freeze protection to learn more »

Additional information

1. World Health Organization (WHO), UNICEF, World Bank. State of the World’s Vaccines and Immunization. Third edition. Geneva: WHO; 2009.

2. WHO. The Global Burden of Disease: 2004 Update. Geneva: WHO; 2008. Available at: