PneumoCarr

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:: The rational of the PneumoCarr project


Roadblocks in the current use and evaluation of new pneumococcal vaccines

An important recent addition to the tools for combating pneumococcal disease is the pneumococcal conjugate vaccine (PCV) that is protective already in early infancy. Indeed, infant immunization with PCV offers a realistic possibility to achieve the UN Millennium goal of a 2/3 reduction of deaths of those under 5 years of age.

However, for this potential of PCV to become reality the vaccine would need to be used widely in the developing countries. At the moment there are important roadblocks making this realization slow and doubtful. A major such roadblock is the complexity and cost of clinical trials to estimate the efficacy and expected effectiveness of the vaccine in the target populations. The conventional efficacy trial for PCV is based on demonstration of invasive pneumococcal disease (IPD) in a serotype-specific manner, which requires a large sample size of tens of thousands vaccinees a careful clinical (X-ray) and laboratory follow up, difficult to implement in developing country settings. As a surrogate for the requirement of the IPD endpoint a serological threshold value ?predictive of protection? has been sought but is not attainable at the serotype level.

This roadblock is an important impediment to governments for making decisions about including PCV in their national immunization programs, to international bodies like WHO for issuing recommendations concerning PCV and to the vaccine industry to develop PCV products (currently there exists only one licensed PCV, produced by a multinational company). In lack of competition, the price of PCV will remain high in relation to the health budgets of the countries most in need of it, and vaccine supply in quantities required globally will be hard to assure.

Change of the research focus into carriage

As a solution to the above roadblock we propose reduction of pneumococcal colonization as an alternative or additional endpoint in vaccine trials. The advantage gained would be enormous in terms of both sample size required and ease of endpoint detection. This approach has furthermore the beauty of focusing on the first step of pneumococcal infection, transmission of the bacteria measured as colonization or acquisition of carriage, i.e. the point of increased risk of progression of colonization to disease. Reduction of colonization is furthermore responsible for the indirect population-wide effects (herd immunity) of the vaccine, according to recent experience in the USA, an essential component of the protective effectiveness of PCV.

Meeting the Objectives

  • Develop the scientific basis and analytic tools to assess VE-colonization of PCV products for both licensure and public health purposes.
    • Develop a model for the dynamics of pneumococcal nasopharyngeal (NP) colonization without the influence of PCV (taking into factors such as age, force of infection, exposure to pneumococci, multiple serotype colonization risk). Develop a trial protocol for VE-colonization endpoints.
    • Develop a method to estimate VE-colonization for vaccine serotype strains taking into consideration the covariates now understood from the ?dynamics of pneumococcal NP colonization? model.
    • Fill the gaps in the knowledge about VE-Colonization and validate the VE-colonization model with the use of new data collected during the PneumoCarr project.
    • Develop a model to correlate VE-colonization with serotype specific immunity.
    • Develop a model to predict long-term effects of PCV on colonization and invasive pneumococcal disease.


  • Promote among the technical community an improved understanding of the value of VE-colonization for PCV licensure and public health purposes
    • Summarize the existing knowledge of pneumococccal colonization, disease, and the effect of vaccination
    • Hold workshops for technical experts for the discussion of NP colonization as a licensure pathway.
    • Engage with regulatory authorities at workshops on NP colonization.
    • Hold specific discussions with regulatory authorities to reach agreement on the data needed for the use of VE-colonization as part of the process of licensure.