WIW 2016: ISGlobal – developing the next generation of vaccines

Eoghan Walsh Youth Empowerment

World Immunisation WeekAs we continue our coverage of World Immunisation Week, and survey the field for the next generation of vaccines, Quique Bassat of ISGlobal talks about the work that they do at their Barcelona-based organisation on disease and vaccine research. For more information on the series click here!

Introducing the Barcelona Institute for Global Health (ISGlobal)

ISGlobalThe Barcelona Institute for Global Health (ISGlobal) is the result of an innovative alliance between academic, government, and philanthropic institutions to contribute to the efforts to address the most pressing challenges in global health. Our mission is to improve global health and promote health equity through excellence in research and the translation and application of knowledge. Our work model is aimed to generate knowledge by doing research and to convey it and turn it into action through our Training & Education and Policy & Global Development areas.

IGlobal is currently undergoing a merging process with the Centre for Research in Environmental Health (CREAL). As an outcome of that process, the resulting institute is expected to become one of the main global health organizations in Europe.

Our current research agenda includes both communicable diseases (malaria, HIV/AIDS, maternal, child and reproductive health, Chagas disease and other neglected tropical diseases and viral and bacterial infections) and non-communicable diseases and environmental health (cancer, child health, respiratory diseases, air pollution, water pollution and radiation).

ISGlobal’s vaccine development efforts

ISGlobal has been the pioneer of malaria vaccine development in malaria-endemic areas. With over two decades of field trial experience, researchers from our group have tested various malaria vaccine candidates and contributed significantly to the clinical and immunological evaluation of the –to date- only registered malaria vaccine, RTS;S (Mosquirix©). Through its long-lasting collaboration with the Manhiça Health Research Centre (CISM); in Mozambique, our group was able to test for the first time this vaccine in a Phase II study in over 2,000 African children 1-4 years of age, starting in the year 2003. This study, which continued for over 4 years, demonstrated a good safety and tolerability profile of the vaccine candidate, a high efficacy, and duration of protection lasting for at least 4 years.

This study was continued with a smaller proof-of-concept of the same endpoints when the vaccine was administered in newborns, alongside the timing of the expanded Programme of Immunization (EPI) vaccines, understanding that the EPI platform was the naturally existing delivery mechanism in countries where access to the health system would not necessarily guarantee adequate access to health beyond the first vaccination visits in early childhood. Such promising results led to the design and implementation of a much larger Phase III study conducted in seven African countries, and enrolling over 16,000 children, CISM being one of the sites again.

Beyond malaria vaccine development, and always at the Manhiça site, ISGlobal has also contributed to the clinical evaluation of vaccines against other diseases, including the AERAS-402 construct against tuberculosis, or the post-registration evaluation of the feasibility of implementation of the human papilloma virus vaccine in 3 districts in Mozambique.

Our Future plans – developing the next generation of malaria vaccines

Understanding that the efficacy conferred by the RTS,S vaccine is imperfect, ISGlobal remains committed to the development of the next generation of malaria vaccines. Plans include the possibility of testing in the field both the novel sporozoite-based vaccine (Sanaria) together with the evaluation of chemo-attenuation strategies (based on the inoculation of attenuated sporzoites alongside a curative dose of an effective antimalarial). Besides malaria, ISGlobal is also interested in the evaluation of vertical immunization strategies, which include the vaccination of pregnant women with a vaccine designed principally to protect the health of their offspring.

In this respect, ISGlobal has conducted preparatory work to allow its participation in future trials of new vaccines against Group B Streptococcus (a major cause of neonatal morbidity and mortality) and respiratory syncytial virus (RSV, which causes substantial disease in the very young infant, and thus could prove challenging to protect with conventional paediatric vaccination strategies). Finally, ISGlobal, with an extensive research portfolio in Neglected Tropical Diseases, also pursues the development and evaluation of a future vaccine against Chagas disease.

Challenges ahead for vaccine development

The clinical development of vaccines not naturally destined for their use or implementation in developed countries (malaria being a paradigmatic example) faces many challenges difficult to surpass. The first and obvious one is financial, as funding to conduct field trials of such vaccine is less readily available than that for vaccines which would have a direct applicability also in developed countries. In this respect, the appearance in the last years of philanthropic funding, such as for instance that provided by the Bill and Melinda Gates Foundation, has been an invaluable asset and significantly contributed to a renewed push for vaccine development.

In the absence of naturally occurring correlates of protection (such as the ones well tested and demonstrated for other infectious diseases such as flu, or hepatitis B as an example), vaccine evaluation relies on the demonstration of a reduced incidence of new infections in the group receiving the vaccine candidate, as opposed to its controls. This need for natural exposure to evaluate trial outcomes obliges the studies to take place in endemic areas, increasing the costs and logistic complexities for trials that due to their numbers, would already be tremendously challenging to implement. They also require the adequate understanding of the socio-anthropological and cultural contexts of vaccine uptake and acceptability in the areas where the trials would be conducted.

Finally, although researchers may be very well aware of these challenges, and have the adequate knowledge and expertise to work in such settings and contexts, the necessary partnerships with industry developers, and the relatively fragile regulatory environments, add a layer of complexity that increases the challenges for vaccine development in such endemic areas.


Quique Bassat is a researcher at the Barcelona Institute for Global Health (ISGlobal).