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PERtussIS COrrelates of Protection Europe - Sofia ref.: 115910

Periodic Reporting for period 5 - PERISCOPE (PERtussIS COrrelates of Protection Europe - Sofia ref.: 115910)

Reporting period: 2020-01-01 to 2021-02-28

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 fifth year accomplished the following key objectives:
A Controlled Human Challenge Model (HCM) of B. pertussis has been successfully established at the NIHR Wellcome Trust Clinical Research Facility in Southampton, UK by the Consortium. In phase A of the program, serological analysis showed that volunteers who show nasal colonisation with B. pertussis bacteria, also exhibit an increase in circulating antibodies against pertussis PT antigen, which is not detected in the volunteers who were not colonised. An early IgA and IgG mucosal antibody recall response was only detected in individuals who controlled bacterial colonisation, not in those who were not colonised. Analysis of blood cell populations also showed a systemic pertussis-specific T-cell immune response after bacterial colonisation and mobilisation of the B cell compartment in response to infection. A new clinical study (Phase B) was launched in 2019 to confirm and expand on Phase A observations. During the past year, the Phase B study was severely affected by the COVID pandemic and recruitment was temporarily stopped. After successful reactivation, enrolment has restarted, albeit at a slower pace, as COVID containment measures are still in place in the UK.
The BERT study (Booster pertussis vaccine study), conducted under the sponsorship of RIVM (NL), the Oxford Vaccine Group (UK) and Turku University Hospital (Finland), has completed all follow ups in 2020. 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 have been 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 February 2019. The aim of this study is to investigate differences in the humoral and cellular response to whole-cell or acellular pertussis vaccination in infants born to mothers who are randomized to receiving or not pertussis vaccine during pregnancy. The trial was severely disrupted by the COVID-pandemic with recruitment pauses on two occasions. Despite these challenges, new recruitment is about to be completed and follow up is ongoing as planned. A second recruitment site was opened in mid-January 2020.
The 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. Enrolment was ready to commence in March 2020 but was interrupted by the COVID pandemic. Recruitment was relaunched in March 2021 and is proceeding well since then.
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 born to mothers who did not receive pertussis vaccination during pregnancy. Despite the pandemic, the MIFI study has overall progressed as planned during the past year.
Notable achievements in earlier years were expanded in year 5 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 vaccines prime CD4 TRM cells that sustain protective immunity against nasal colonization with Bp. Additional experiments to explore biomarkers in this model are ongoing.
Further substantial progress was made in the development and qualification of the 14 novel immunological assays deployed to study the response to infection and vaccination in clinical and preclinical studies. Systems immunology tools have also been deployed (CyTOF mass cytometry and single-cell RNAseq) to analyse biological samples collected from the human challenge colonisation study (HCM)-, and the vaccination studies.
PERISCOPE has established a multidisciplinary bioinformatics analysis platform and a biobank for sample storage from pre-clinical and clinical studies. Data standardization by CDISC has been set up. The tranSMART data base is up and running and now contains RNAseq and antibody data from the HCM and the BERT study.
In year 5 of PERISCOPE 2 newsletters were published, 6 scientific manuscripts on research outcomes were published. PERISCOPE partners participated in 6 conferences with presentations and poster contributions.
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. Despite the impossibility of having in-person meetings, a variety of online discussion forums and meetings have been held in year 5 of PERISCOPE where areas for future work were identified, new interfaces created and collaborative links strengthened among the partners. 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.