Influenza roadmap:
Vaccines
Roadmap for the development of candidate vaccines for influenza
Download Influenza-vaccine-development-roadmap1
Vaccine
Dependencies
- 2 Naturally attenuated candidates
- 2A Safety
- 2B Delivery route
- 2C Delivery platform
- 2D Efficacy in challenge model
- 3 Rationally attenuated candidates
- 3A Safety
- 3B Delivery route
- 3C Delivery platform
- 3D Efficacy in challenge model
- 4 Inactivated vaccines
- 4A Safety
- 4B Delivery route
- 4C Delivery platform
- 4D Efficacy in challenge model
- 5 DNA/RNA
- 5A Safety
- 5B Delivery route
- 5C Delivery platform
- 5D Efficacy in challenge model
- 6 Subunit vaccines
- 6A Safety
- 6B Delivery route
- 6C Delivery platform
- 6D Efficacy in challenge model
- 7 Vectored vaccines
- 7A Safety
- 7B Delivery route
- 7C Delivery platform
- 7D Efficacy in challenge model
Vaccine
Research Question
- Develop vaccines with DIVA tests that can be rapidly modified and suitable for mass – administration such as spray, feed or
water or in ovo application - Mucosal vs systemic protection vaccine
- Vaccine protection whole year or specific period of time or season
- Develop potent vaccines for less immunogenic influenza subtypes (e.g. H9, H7 )
- Development of protective vaccines to prevent outbreaks of influenza in poultry, horses and swine
Research Gaps and Challenges
- Develop and transfer a process to select and update antigenic epitopes in vaccines based on regional circulating influenza viruses
- Develop and validate DIVA tests for specific vaccine technologies
- Develop and validate multi – species vaccine platforms that are broadly cross-protective: a universal flu vaccine
- Detection systems for vaccine failure
- Understanding the role of vaccines in driving escape mutations, and how to prevent them
- How to evaluate levels of residual virus in vaccinated animals (Vaccination may not result in sterile immunity)?
- Quick development and scale-up of vaccines
- Correlates of protection: what are the minimum levels of HA antigen-specific antibodies (Hi, ELISA/or VN) of each of the different formulations of unconventional vaccines e.g. (vectored/subunit) that could induce complete protection from clinical diseases as well as hidden impacts such as reduction in egg
production or compromised resistance from other respiratory infections? - How to evaluate levels of residual virus in vaccinated animals (i.e. is lack of sterilizing immunity is a concern)
- Develop appropriate vaccine protocols (How many doses of each vaccine H5, H7 or H9 or H6?Single or multivalent vaccine?)
- Is there a practical way to vaccine wild birds
- Vaccination should be acceptable for international trade
- What is the underlying driver for increased breadth of cross protection?
Solution Routes
- Testing of nucleic acid-based, vectored, inactivated or subunit vaccine candidates
- Assessment of novel vaccines according to their ability to prevent infection and transmission for prolonged periods post-immunization
- Vaccine performance under field conditions/studies that validate
laboratory models of vaccination by comparison to field conditions - Novel antigen / vaccine designs in industry
Vaccine platforms that express different multiple antigens(multivalence constructs) - Ability to compare recently developed vaccine constructs head-to-head in sufficiently sized studies to quickly reach conclusions
on usefulness of novel concepts using established criteria (mRNA vaccines, ORF vectored IAV, bivalent LAIV with elastase
dependence strains, computationally, optimized HA antigens in various vectors, chimeric bat NS1-truncated, MLVs, etc.) - Develop alternative to eggs culture for vaccine production – i.e. development of tissue culture system
- Research on the various combinations included in the definition of “heterologous prime/boost”
Dependencies
- Critical to develop an “adequate surveillance program” that can be implemented with any vaccination strategy to meet trade requirements (IABS meeting 2022) (see disease control roadmap)
- Design vaccination strategies that fit species, age, production type and maternal antibody status including priming and boosting with various technologies to optimize protection and duration of immunity (see disease control roadmap)
- Develop serological or other in vitro correlates / tests for assessing vaccine protection
- Development of nucleic acid-based, vectored, inactivated or subunit vaccines
- Diagnostic kits for DIVA compatible vaccines – need to get industrial partners involved
- Quick development of vaccine (also not DIVA) to respond rapidly to disease outbreak management during emergency (pandemic/epidemic emergency)
- Correlates/tests for vaccine protection in avian species and swine
- Knowledge on vaccine effectiveness in different ages
State Of the Art
- Many DIVA compatible vaccines developed without associated diagnostic kits.
- More Difficult DIVA when more than one AIV coinfecting viruses and multiple subtypes of vaccines are used such as H5, H7 and
H9. - The minimum requirement of HI titers in field vaccinated birds, there is a description in OIE terrestrial manual 2012 chapter 3.3.4, C requirements for vaccine 2.3.2. It says, 1/32 to protect from mortality or greater than 1/128 to provide reduction in challenge virus replication and shedding
Projects
What activities are planned or underway?
Protect wildlife from livestock diseases.
Planned Completion date 07/10/2022
Participating Country(s):
Netherlands
Dynamics of sustainability in integrated agriculture : aquaculture systems in the Mekong Delta
Planned Completion date 21/10/2024
Participating Country(s):
Netherlands