Periodic Reporting for period 3 - INCENTIVE (Indo-European Consortium for Next Generation Influenza Vaccine Innovation)
Reporting period: 2023-08-01 to 2025-01-31
The highly integrated INCENTIVE consortium is a partnership between Indian and European/US groups that addresses the global health and economic challenge posed by influenza infections, to reduce the worldwide burden resulting from outbreaks. INCENTIVE’s strategic goals are to provide seminal knowledge on the underlying mechanisms of poor responsiveness to influenza vaccines in vulnerable individuals and advance the development of two next generation universal influenza vaccines. This is achieved by pursing the following specific objectives:
1) address the current knowledge gap by performing comprehensive immunome profiling of responders and non-responders to licensed influenza vaccines in infants, children and elderly in parallel phase IV trials in Europe and India to identify the underlying mechanisms of vaccine responsiveness in different vulnerable populations and ethnical groups; 2) advance the development of two next generation universal vaccines, including an antigen presenting cell-targeted nucleic acid vaccine up to proof-of-concept for vaccine efficacy in non-human primates, and a computationally-derived second generation mucosal COBRA (Computationally-Optimized Broadly-Reactive Antigens) vaccine up to clinical development, comprising a phase I trial in Europe, a phase II trial in India and efficacy studies using an influenza controlled human challenge model; 3) identify predictive biomarkers of responsiveness to vaccination to develop new diagnostics; 4) implement comprehensive technology transfer and harmonization activities for immunological analysis and data integration; and 5) perform a health systems and investment analysis, and discrete choice experiments to assess the suitability of the developed technologies for low- and middle-income countries and to identify potential downstream constraints that might affect uptake by health care systems.
1) address the current knowledge gap by performing comprehensive immunome profiling of responders and non-responders to licensed influenza vaccines in infants, children and elderly in parallel phase IV trials in Europe and India to identify the underlying mechanisms of vaccine responsiveness in different vulnerable populations and ethnical groups; 2) advance the development of two next generation universal vaccines, including an antigen presenting cell-targeted nucleic acid vaccine up to proof-of-concept for vaccine efficacy in non-human primates, and a computationally-derived second generation mucosal COBRA (Computationally-Optimized Broadly-Reactive Antigens) vaccine up to clinical development, comprising a phase I trial in Europe, a phase II trial in India and efficacy studies using an influenza controlled human challenge model; 3) identify predictive biomarkers of responsiveness to vaccination to develop new diagnostics; 4) implement comprehensive technology transfer and harmonization activities for immunological analysis and data integration; and 5) perform a health systems and investment analysis, and discrete choice experiments to assess the suitability of the developed technologies for low- and middle-income countries and to identify potential downstream constraints that might affect uptake by health care systems.
The INCENTIVE management and coordination framework continues to be operational (WP1). Two vaccine strategies (COBRA vaccine adjuvanted with c-di-AMP and APC-MIX DNA Vaccine) have advanced in pre-clinical evaluation. Immunogenicity and challenge studies in small animals (COBRA vaccine adjuvanted with c-di-AMP in mice and ferrets, and APC-MIX in mice) have shown robust immune responses and efficacy. Immunogenicity and challenge studies in non-human primates (NHP) are under way. Vaccine immunogens to be used for vaccination of NHPs have been prepared. The first study to estalish the infection model in NHPs has been successfully completed (WP3). With respect to the adjuvant, stability tests were continued and storage temperatures calculated (WP2).
Phase IV clinical trials with a commercially available influenza vaccine (QIV) include three age groups: 1) elderly ≥ 60 years (QIV-1); 2) children 3-11 years (QIV-2); and 3) infants 6-8 months (QIV-3). The trials have been completed in Europe. In India, QIV-1 and QIV-2 have been completed, and QIV- 3 is ongoing (WP4).
In depth immunological analysis of the Phase IV QIV trial samples is ongoing revealing important quantitative and qualitative differences in immune responses to influenza vaccination between different age groups (WP5).
The “data warehouse” in Europe and India has been established. It is implemented as FAIR Data Points (FDPs) distributed across the sites generating the data. All the FDPs have been deployed in Europe/India and data is being currently uploaded (WP6).
Harmonization of the clinical trials and procedures have been successfully managed. Support for the implementation of immunological readouts, such as serology, T- and B-cell responses between the European and Indian partners has continued (WP7).
For the study for eliciting preferences towards influenza vaccines and vaccination amongst the phase IV QIV trial participants in India, a Discrete Choice Experiment (DCE) was performed with the QIV-1 cohort. Data analysis for this continues to advance. The health facility assessment survey across 51 public health facilities in Sonipat and Visakhapatnam districts in India have been completed. DCE among 1600 participants in these districts have also been completed. Additionally, the Influenza-like illness (ILI) surveillance application prototype and dashboard have been developed, piloted and adapted during this period by the Indian partners. Moreover, the scoping review protocol was developed and validated by the European partners (WP8).
Phase IV clinical trials with a commercially available influenza vaccine (QIV) include three age groups: 1) elderly ≥ 60 years (QIV-1); 2) children 3-11 years (QIV-2); and 3) infants 6-8 months (QIV-3). The trials have been completed in Europe. In India, QIV-1 and QIV-2 have been completed, and QIV- 3 is ongoing (WP4).
In depth immunological analysis of the Phase IV QIV trial samples is ongoing revealing important quantitative and qualitative differences in immune responses to influenza vaccination between different age groups (WP5).
The “data warehouse” in Europe and India has been established. It is implemented as FAIR Data Points (FDPs) distributed across the sites generating the data. All the FDPs have been deployed in Europe/India and data is being currently uploaded (WP6).
Harmonization of the clinical trials and procedures have been successfully managed. Support for the implementation of immunological readouts, such as serology, T- and B-cell responses between the European and Indian partners has continued (WP7).
For the study for eliciting preferences towards influenza vaccines and vaccination amongst the phase IV QIV trial participants in India, a Discrete Choice Experiment (DCE) was performed with the QIV-1 cohort. Data analysis for this continues to advance. The health facility assessment survey across 51 public health facilities in Sonipat and Visakhapatnam districts in India have been completed. DCE among 1600 participants in these districts have also been completed. Additionally, the Influenza-like illness (ILI) surveillance application prototype and dashboard have been developed, piloted and adapted during this period by the Indian partners. Moreover, the scoping review protocol was developed and validated by the European partners (WP8).
INCENTIVE will develop a novel next generation universal vaccines that will provide a considerable broader protection against both co-circulating seasonal influenza strains over multiple seasons, as well as against pre-pandemic strains from subtypes that do not currently circulate in the human population. The safety, immunogenicity and efficacy studies for COBRA vaccine (in combination with the adjuvant c-di-AMP) and APC-MIX in Non-Human Primates (NHPs) will provide the proof-of-concept for further development of these experimental vaccines for the protection against seasonal and pandemic influenza. INCENTIVE will also perform phase IV clinical studies in vulnerable populations in Europe and India, and the comprehensive immune monitoring and profiling data obtained will contribute towards the identification of biomarkers and correlates of protection, which can facilitate the development of diagnostics for stratification and follow-up of vaccines, as well as the establishment of tailored vaccination strategies for poor responders. In summary, the development of knowledge and technologies for innovative next generation vaccines against influenza across European and Indian sites will have a significant impact on morbidity and mortality, human suffering and disability, and associated care costs. It will impact the quality of life of families, communities and nations. The development of cost- and time-efficient GMP manufacturing of vaccine components in India, and the inclusion of influenza vaccination in national programs will also facilitate effective implementation and quicker uptake by health systems with limited resources.