Periodic Reporting for period 1 - CHIKVAX_CHIM (Late-stage clinical development of Chikungunya vaccines in endemic countries (CHIKV) and Controlled Human Infection Models for SARS-CoV2 and other beta coronaviruses (CHIM).)
Reporting period: 2023-06-01 to 2024-11-30
This project focuses on two disease areas each with respective objectives and pathways to impact.
The first disease of focus is Chikungunya, a viral disease caused by the Chikungunya virus belonging to the Togavirus viral family. Chikungunya is most commonly transmitted by female Aedes aegypti and Aedes albopictus mosquitoes and is typically characterised by fever and severe joint pain, which is often debilitating and can last for weeks, months or even years, severely impacting quality of life. WHO has identified Chikungunya as a major public health concern due to its high morbidity and has stated that further research and development is needed to mitigate the risk it poses. Chikungunya was first identified in Tanzania in 1952 and since 2004 major epidemics have been reported in Africa and Asia, and local transmission is also now being reported in Europe, the USA and the Caribbean. In 2024, approximately 480,000 Chikungunya cases have been reported, with over 190 deaths. Over 400,000 cases were detected in Brazil alone in 2024. Today, over a billion people live in areas where Chikungunya is endemic and climate change could further amplify the threat posed.
Through previous support from the European Union’s Horizon Europe programme, one vaccine candidate in active development —developed by French pharmaceutical company Valneva—has become the first in the world to be approved by Stringent Regulatory Authorities (by the US FDA, Health Canada and European EMA). Valneva is now pursuing licensure for their vaccine in Brazil with CEPI’s support.
This project aims to build on this and:
• Generate additional data to potentially support extending use of Valneva's Chikungunya vaccine in Chikungunya-endemic countries such as Brazil. The research could also support the evidence based for use of the vaccine in vulnerable populations at risk of being infected with this debilitating mosquito-borne disease including children, adolescents and pregnant women.
• Enable technology transfer of the vaccine drug product to an additional vaccine manufacturer to accelerate and expand access to Valneva's Chikungunya vaccine in Asian low- and middle- income countries that are vulnerable to chikungunya outbreaks.
• Further advance other vaccine candidate(s) that are near or have achieved regulatory licensure into phase IV clinical trials in endemic countries.
The second disease area of focus looks at coronaviruses. The multiple successful COVID-19 vaccines that were so rapidly developed and widely deployed during the coronavirus pandemic were lifesavers. They prevented COVID-19 from killing millions more people and marked a remarkable scientific advance in the pace at which the world was able to respond to an outbreak of a novel viral disease. But although the vaccines that were developed against SARS-CoV2 were effective in preventing moderate and severe disease, none of the current licensed COVID-19 vaccines have shown significant effect in preventing people from becoming infected. It is therefore important to understand the underlying mechanisms of mucosal immune responses protecting the upper airways from infection and transmission, and to identify immune markers associated with protection against infection and human-to-human transmission. Enhancing this body of knowledge would significantly support the development of novel mucosal vaccines targeting the prevention of infection and/or human-to-human transmission.
Since breaking the chains of respiratory viral human-to-human transmission is critical to stopping outbreaks of epidemics before they expand into pandemics, the project will use so-called "human challenge" studies to discover how best to evaluate, monitor and design novel mucosal vaccines that could provide a particular type of immunity — mucosal immunity — that can stop viruses from infecting the body in the first place. Challenge trials can be used to assess vaccine candidates and vaccine technology by infecting healthy volunteers with a coronavirus in a controlled environment, followed by close monitoring of safety, viral infection, and immunogenicity. This approach helps to gain a deeper understanding of whether, and how, an experimental mucosal vaccine works. The objective of the project is to build a network of partners that will establish a toolbox for a human-challenge-model platform to test novel mucosal vaccine candidates against betacoronaviruses (the sub-family of coronaviruses that includes the SARS-CoV2 virus) the MERS coronavirus that causes Middle East Respiratory Syndrome, and also seasonal coronaviruses.
The first disease of focus is Chikungunya, a viral disease caused by the Chikungunya virus belonging to the Togavirus viral family. Chikungunya is most commonly transmitted by female Aedes aegypti and Aedes albopictus mosquitoes and is typically characterised by fever and severe joint pain, which is often debilitating and can last for weeks, months or even years, severely impacting quality of life. WHO has identified Chikungunya as a major public health concern due to its high morbidity and has stated that further research and development is needed to mitigate the risk it poses. Chikungunya was first identified in Tanzania in 1952 and since 2004 major epidemics have been reported in Africa and Asia, and local transmission is also now being reported in Europe, the USA and the Caribbean. In 2024, approximately 480,000 Chikungunya cases have been reported, with over 190 deaths. Over 400,000 cases were detected in Brazil alone in 2024. Today, over a billion people live in areas where Chikungunya is endemic and climate change could further amplify the threat posed.
Through previous support from the European Union’s Horizon Europe programme, one vaccine candidate in active development —developed by French pharmaceutical company Valneva—has become the first in the world to be approved by Stringent Regulatory Authorities (by the US FDA, Health Canada and European EMA). Valneva is now pursuing licensure for their vaccine in Brazil with CEPI’s support.
This project aims to build on this and:
• Generate additional data to potentially support extending use of Valneva's Chikungunya vaccine in Chikungunya-endemic countries such as Brazil. The research could also support the evidence based for use of the vaccine in vulnerable populations at risk of being infected with this debilitating mosquito-borne disease including children, adolescents and pregnant women.
• Enable technology transfer of the vaccine drug product to an additional vaccine manufacturer to accelerate and expand access to Valneva's Chikungunya vaccine in Asian low- and middle- income countries that are vulnerable to chikungunya outbreaks.
• Further advance other vaccine candidate(s) that are near or have achieved regulatory licensure into phase IV clinical trials in endemic countries.
The second disease area of focus looks at coronaviruses. The multiple successful COVID-19 vaccines that were so rapidly developed and widely deployed during the coronavirus pandemic were lifesavers. They prevented COVID-19 from killing millions more people and marked a remarkable scientific advance in the pace at which the world was able to respond to an outbreak of a novel viral disease. But although the vaccines that were developed against SARS-CoV2 were effective in preventing moderate and severe disease, none of the current licensed COVID-19 vaccines have shown significant effect in preventing people from becoming infected. It is therefore important to understand the underlying mechanisms of mucosal immune responses protecting the upper airways from infection and transmission, and to identify immune markers associated with protection against infection and human-to-human transmission. Enhancing this body of knowledge would significantly support the development of novel mucosal vaccines targeting the prevention of infection and/or human-to-human transmission.
Since breaking the chains of respiratory viral human-to-human transmission is critical to stopping outbreaks of epidemics before they expand into pandemics, the project will use so-called "human challenge" studies to discover how best to evaluate, monitor and design novel mucosal vaccines that could provide a particular type of immunity — mucosal immunity — that can stop viruses from infecting the body in the first place. Challenge trials can be used to assess vaccine candidates and vaccine technology by infecting healthy volunteers with a coronavirus in a controlled environment, followed by close monitoring of safety, viral infection, and immunogenicity. This approach helps to gain a deeper understanding of whether, and how, an experimental mucosal vaccine works. The objective of the project is to build a network of partners that will establish a toolbox for a human-challenge-model platform to test novel mucosal vaccine candidates against betacoronaviruses (the sub-family of coronaviruses that includes the SARS-CoV2 virus) the MERS coronavirus that causes Middle East Respiratory Syndrome, and also seasonal coronaviruses.
Activities and key achievements in the first 18 months include:
For CHIM:
- Imperial College London Contract Signature
- Regulatory approvals for CHI Study #1
- First Subject First Visit CHI (University Oxford (Study 1)
- Selection of Vaccine Candidate confirmed.
For CHIK:
- Ongoing review of the marketing authorisation application for IXCHIQ by the Brazilian Health Regulatory Agency (ANVISA)
- Preparations for Phase 4 effectiveness studies following encouraging Phase 3 data
- License agreement signed with SII to conduct a technology transfer of the current drug product manufacturing process, enabling access in Asia
For CHIM:
- Imperial College London Contract Signature
- Regulatory approvals for CHI Study #1
- First Subject First Visit CHI (University Oxford (Study 1)
- Selection of Vaccine Candidate confirmed.
For CHIK:
- Ongoing review of the marketing authorisation application for IXCHIQ by the Brazilian Health Regulatory Agency (ANVISA)
- Preparations for Phase 4 effectiveness studies following encouraging Phase 3 data
- License agreement signed with SII to conduct a technology transfer of the current drug product manufacturing process, enabling access in Asia
There expected impacts of the work under CHIK are as follows:
o Scientific: this project will contribute to specific scientific advances by developing an animal primate model for CHIKV vaccines and to establish a correlate of protection/efficacy using human antibody transfer and established a neutralizing antibody titer of protection; this work will validate several vaccine platforms effective in producing protection of infection; and utilization of an antibody standard will harmonize data results across numerous studies.
o Economic/technological: an effective CHIKV vaccine will reduce DALYs loss from CHIKV infection which will reduce the economic burden of outbreaks on low-resource countries; technology transfer and local manufacturing will decrease vaccine costs and bring new business process and products to the market increasing efficiency, and quality standards.
o Societal: an effective CHIKV vaccine will significantly reduce DALYs lost from this disease and decrease morbidity and mortality to vulnerable subpopulations; in addition, proactively educating and assisting countries to develop CHIKV vaccine program will improve policy, decision making and raise consumer awareness.
There are several expected impacts of the work under CHIM:
· Scientific: 1) Defined procedures to conduct CHIM using betacoronaviruses in non-naïve population; 2) Demonstration of reduced risk of infections/transmission following vaccination and; 3) Determined mucosal immune markers associated with reduced risk of infection/transmission.
· Economic: 1) Impact on the general human population regarding the viral spread of coronaviruses; 2) Accelerated testing of transmission-blocking vaccines and implementation of these vaccines will impact the viral spread and thereby reducing the risk of emergence of novel variants.
· Societal: 1) Reducing the spread of a virus will reduce the risk of novel variants and have a positive impact on the population at risk. In vulnerable populations, for example, vaccines might be less effective against severe disease, so it is important to greatly minimise the spread within the general population and thereby protect individuals at risk.
o Scientific: this project will contribute to specific scientific advances by developing an animal primate model for CHIKV vaccines and to establish a correlate of protection/efficacy using human antibody transfer and established a neutralizing antibody titer of protection; this work will validate several vaccine platforms effective in producing protection of infection; and utilization of an antibody standard will harmonize data results across numerous studies.
o Economic/technological: an effective CHIKV vaccine will reduce DALYs loss from CHIKV infection which will reduce the economic burden of outbreaks on low-resource countries; technology transfer and local manufacturing will decrease vaccine costs and bring new business process and products to the market increasing efficiency, and quality standards.
o Societal: an effective CHIKV vaccine will significantly reduce DALYs lost from this disease and decrease morbidity and mortality to vulnerable subpopulations; in addition, proactively educating and assisting countries to develop CHIKV vaccine program will improve policy, decision making and raise consumer awareness.
There are several expected impacts of the work under CHIM:
· Scientific: 1) Defined procedures to conduct CHIM using betacoronaviruses in non-naïve population; 2) Demonstration of reduced risk of infections/transmission following vaccination and; 3) Determined mucosal immune markers associated with reduced risk of infection/transmission.
· Economic: 1) Impact on the general human population regarding the viral spread of coronaviruses; 2) Accelerated testing of transmission-blocking vaccines and implementation of these vaccines will impact the viral spread and thereby reducing the risk of emergence of novel variants.
· Societal: 1) Reducing the spread of a virus will reduce the risk of novel variants and have a positive impact on the population at risk. In vulnerable populations, for example, vaccines might be less effective against severe disease, so it is important to greatly minimise the spread within the general population and thereby protect individuals at risk.