Vaccine development is thriving internationally. Development work is being carried out to control both new and old pathogens. New technologies, especially the mRNA technology familiar from COVID-19 vaccines, are under intense development. In addition to the established major vaccine manufacturers, there are also some new players emerging in the field of vaccine development and manufacturing.

Getting a license is a long process

After laboratory studies, clinical vaccine research involving human subjects focuses particularly on phase I–III studies aimed at obtaining the license for marketing authorization. These studies are important for demonstrating the safety and efficacy of a product before large-scale deployment. In particular, phase III studies aim to demonstrate the relative efficacy of the vaccine against a well-defined confirmed disease case in comparison to a reference product or placebo. This is a prerequisite for obtaining a license from the authorities.

Let’s consider the pneumococcus as a practical example. The pneumococcal vaccines that have been on the market for a long time as well as those that are currently under development are based on the use of capsular polysaccharides as vaccine antigens (that is, as the substances that cause the formation of antibodies in the body). More than a hundred disease-causing pneumococcal serotypes with different capsular polysaccharide structures have already been detected. The types that most commonly cause invasive disease (sepsis and meningitis) have been selected for the vaccines. Phase III studies have shown excellent efficacy against invasive pneumococcal disease caused by the serotypes included in the vaccines.

Ten of our vaccine research clinics around Finland specialize in these kinds of phase I–III trials, aiming at obtaining the license for marketing authorization. In these studies, we actively cooperate with all major vaccine manufacturers.

National vaccination programs

The most significant benefit from vaccines is gained when they are included in the national vaccination program and administered on a large scale. The large-scale deployment is preceded by a detailed evaluation of the public health benefits of the vaccination program as well as its costs and safety on the individual and population level. Carrying out a cost-effectiveness analysis such as this requires diverse information, which phase I–III studies do not always provide. For example, more information is needed on the disease burden and its cost implications, the costs of administering the vaccine, and the effectiveness of the vaccine in routine use.

The decision on the inclusion on a vaccination program requires an assessment of how much the program can reduce the total number of cases in the target group. This data can be evaluated by combining observational disease burden data with clinical phase 3 vaccine efficacy results utilizing, for example, mathematical modeling. In addition, the effectiveness of the vaccination program can be evaluated in observational studies after the large-scale deployment of the vaccine in the program. However, this data is obtained retrospectively. It may also contain significant inaccuracies and uncertainties. If that is the case, the decision to include a vaccine in the national vaccination program might not be made and the benefits of a program will not be achieved.

Extensive pragmatic trials: the big picture

Our new special-assignment company of the state, FVR – Finnish vaccine research, allows our partners to provide evidence on the public health effects of vaccines, as we can carry out extensive pragmatic clinical trials reliably, efficiently, and with high quality. The focus will be more widely on all benefits and harms of the vaccine, as these are evaluated as comprehensively as possible. With the randomized trial design the aim is to demonstrate in particular the absolute public health benefits of the vaccine, in other words, to show how much of the disease burden the vaccine can reduce.

In the example of a pneumococcal vaccine, this could be, for example, a reduction in hospitalizations due to pneumonia. In this case, the focus is not primarily on the reduction of a relatively rare vaccine-type invasive disease, but on the significantly more common pneumonia and respiratory infections on the whole. In other words, the aim is to see the big picture: the overall reduction in pneumonia, which is the net effect of the reduction in the vaccine-type pneumococci, the possible increase (replacement) by non-vaccine serotypes and other microbes that cause pneumonia; and the disease burden of pneumonia as a whole, including sequelae and the healthcare resources spent on them.

Finland offers exemplary research conditions

Finland has excellent opportunities for conducting these kind of extensive pragmatic trials. The Population Information System, national health registers, comprehensive health care system, cooperation with public health care, and trained personnel provide excellent tools for conducting the studies in an innovative, efficient and reliable way. This is an opportunity to play a key role at the forefront of international vaccine research, working toward improved vaccine development and health security. One of our greatest assets is the educated and health-conscious people, who make it possible for us to carry out the studies through their voluntary participation. In our vaccine trials, we can, in return, offer them tomorrow’s vaccines already today.