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PERtussIS COrrelates of Protection Europe - Sofia ref.: 115910

Periodic Reporting for period 4 - PERISCOPE (PERtussIS COrrelates of Protection Europe - Sofia ref.: 115910)

Reporting period: 2019-01-01 to 2019-12-31

PERISCOPE was created to facilitate the development of a new generation of pertussis vaccines by increasing collaboration between Pertussis stakeholders, particularly vaccine developers/manufacturers and the academic and public research communities in Europe. The key objective of the consortium is to gain a better understanding of the immune mechanisms needed to ensure long lasting immunity to Pertussis in humans. This is to be achieved by developing clinical and preclinical models of pertussis infection and conducting vaccination studies for which a toolbox of several novel immunoassays will be developed and deployed.
PERISCOPE has in its fourth year accomplished the following key objectives:
Phase A of the Control Human Challenge Model (HCM) was successfully completed in 2019 at the NIHR Wellcome Trust Clinical Research Facility in Southampton, UK. Comparisons of immune response parameters in volunteers that were/were not colonised after controlled nasal infection have yielded informative results. Serology tests showed that pertussis nasal colonisation results in detectable increase in blood anti-PT IgG after infection, in culture-positive but not in culture negative infected volunteers. Analysis of mucosal antibody responses showed an early IgA and IgG antibody recall response only in individuals who controlled bacterial colonisation. Analysis of blood cell populations by EuroFlow showed unique mobilization kinetics in the B-cell compartment after infection, suggesting a link to mobilization of an antibody response to infection. Analysis of cellular responses also confirmed the engagement of the systemic T-cell immune compartment after bacterial colonisation.
A protocol amendment to initiate Phase B of the HCM was approved by the Medical Ethical Authorities in the UK and the trail launched in 2019. This study phase will confirm and expand on Phase A observations.
Inclusions in the BERT clinical study (Booster pertussis vaccine study, conducted under the sponsorship of RIVM (NL), the Oxford Vaccine Group (UK) and Turku University Hospital (Finland)) were completed in 2019 and one-year follow-up is being conducted . BERT aims to investigate the effects of aP booster vaccination on the magnitude, quality and persistence of immunological memory against pertussis in children, young adults and elderly with different pertussis epidemiological and priming backgrounds. A large number of biological samples hasbeen analysed using laboratory tests developed by partners. These analyses will allow assessment of biomarkers that can be used to detect early signs of the waning of immunological memory to pertussis. The GaPs study (Gambia Pertussis Study), sponsored by LSHTM, started in January 2019. The aim of this study is to investigate the functional humoral and cellular responses to pertussis vaccination in infants born to mothers who are randomized to receiving or not pertussis vaccine during pregnancy. The trial involves the recruitment of 600 mother/infant pairs. In 2019, more than 104 pregnant women were randomised, 64 children were delivered and 31 infants received their first vaccinations. A second site for inclusion was opened in 2019 and inclusions are running according to the predicted timing. No safety issues have been observed. A large number of biological samples has been transported to the Biobank and initial analyses of T-cell responses and functional antibody tests have been done.
A protocol for the AWARE study, conducted by the Oxford Vaccine Group was approved in 2019 by the MHRA and Medical Ethical Committee in the UK. This is a randomized, open-label controlled study comparing the immune response of infants born to aP vaccinated mothers, to vaccination with either aP- or wP-vaccines. The protocol for the PITA study to analyse pertussis transmission among household contacts of infected children was also approved in 2019 by the Medical Ethical Committees in the Netherlands and Finland.
The Pertussis Maternal Immunization Study in Finland (MIFI) is an open-label study in which the immune responses of infants of aP vaccinated mothers will be compared with those of infants of mothers who did not receive pertussis vaccination during pregnancy. The protocol has been approved by the METC and inclusions started in December 2019.
Notable achievements in earlier years were expanded in year 4 of PERISCOPE, namely:
Work performed in a preclinical murine model (TCD, Ireland) has successfully contributed to new insights into the pathogenesis of pertussis infection. For example, immunization with whole cell but not with acellular pertussis
In addition to the public health objectives of PERISCOPE, the project is being successful in revitalizing and connecting the Pertussis research community in Europe and beyond. This network of stakeholders will continue to contribute to the development of novel vaccines and immunization methodologies beyond the life of the project. A variety of discussion forums and meetings have been held in year 4 of PERISCOPE where areas for future work were identified, new interfaces created and collaborative links strengthened. This has already had a positive impact on the Pertussis community. The active collaboration of industrial and academic partners within the consortium has provided a platform for learning from each other on different approaches and working practices.
The consortium is actively disseminating results of the development of a novel Human Model of infection, with findings already available to the scientific community at large. Data obtained by PERISCOPE partners in preclinical models of infection that confirm the value of a predictive preclinical model of pertussis infection developed by FDA researchers (USA) and expand on their observations, are also being actively disseminated.
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