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A safe DIVA vaccine for African Swine Fever control and eradication

Periodic Reporting for period 1 - VACDIVA (A safe DIVA vaccine for African Swine Fever control and eradication)

Reporting period: 2019-10-01 to 2021-03-31

African Swine Fever (ASF) is one of the most important viral diseases affecting swine, with a serious socio-economic impact. It is present in more than 13 countries in Europe (10 in the EU), 28 sub-Saharan African countries, and 2 Asian countries, China and Mongolia. No vaccine is available and recent incursions in Europe and Asia are jeopardizing the pig industry worldwide. Control of ASF is based on early diagnosis and the implementation of strict sanitary measures. However, measures taken by affected countries have not been sufficient to stop spread.

The objective of VACDIVA is to solve the ASF problem in Europe and affected countries through innovation efforts. VACDIVA will provide:
(1) Three safe and effective pilot vaccines for wild boar and domestic pigs ready for registration;
(2) validated companion DIVA tests and
(3) cost-benefit and effective surveillance and control-vaccination strategies, with field trials in Lithuania and Kenia. Two world leader companies in vaccine production and ASF diagnostic kits will provide production of the new vaccines and DIVA tests. Epidemiological modelling of worldwide scenarios will be offered in a portfolio of services to help animal health authorities control and eradicate the disease. This project will provide policy makers valuable decision support tools to better prevent and control ASF.
VACDIVA counts with the expertise of two world ASF Reference Laboratories (OIE and FAO), the EU reference laboratory (EURL), six EU national Reference Laboratories (of 6 out of the 10 countries currently affected by ASF) and four prestigious ASF research institutions. Participation of Russian, Chinese and African laboratories will provide useful support, increasing acceptance of the vaccines. Active involvement of pig producers, agricultural associations and International agencies like FAO will enlarge the impact of communication, dissemination and training activities.
The work progress during this first period can be summarized as follows:
The candidate Lv17/WB/Rie1 is a naturally attenuated and non-haemodsorbing genotype II African swine fever virus (ASFV), isolated from a hunted wild boar in Latvia in 2017. The preliminary results with this prototype in DP provided the effective dose and route of immunization, with 100% protection against the virulent challenge without clinical signs, cross protection and duration of the immunity. In WB conferred 92% protection against heterologous challenge with a virulent genotype II ASFV isolate. This candidate presents the first report of a promising vaccine against ASF in wild boar by oral administration. Now the project is developing different types of oral baits suitable to wild boar administration systems.
The second vaccine prototype, NH/P68, is a naturally attenuated and non-haemodsorbing genotype I ASFV, isolated from an infected domestic pig in Portugal in 1968. This candidate showed to confer protection against ASF genotypes II and I. This prototype has already been adapted to grow in an established cell line (accepted by EMA regulation for vaccine production) and then evaluated in DP for the efficacy and cross protection capacity. The optimal doses and administration route confers 100% protection in DP against a heterologous ASF virulent genotype II isolate with a significant reduction of side effects if compared to the NH/P68 prototype. In WB it is currently under evaluation, with ongoing work to optimize the doses of immunization and the cross protection against different ASF circulating isolates.
The third prototype, ASF/ARRIAH/CV-1, is an attenuated strain obtained by cell culture passage in Vladimir Laboratory. In contrast to the previous ones, the in vivo protection has not been tested yet.
Two proteins from the first prototype have been described for DIVA test as well as one for the second prototype. DIVA tests will allow to differentiate vaccinated from infected animals. The project has also produced different deletion mutants from the first prototype that are ready for the in vivo evaluation in DP. The partners involved are working to obtain other mutants from the second prototype
The project is also addressing vaccine manufacturing. Since pig blood cells are not an option, some few candidates for cell lines are being already selected.
The ultimate goal of this project is to generate safer and efficacious vaccines with DIVA properties and to develop a control and eradication strategy for the vaccination in different ASF scenarios.
African swine fever (ASF) remains today the biggest threat of the global swine industry, causing serious sanitary and economic consequences. Nowadays, the disease is present in more than 50 countries on four continents (Africa, Europe, Asia and Oceania) and more than 77% of the world swine population is living in affected areas (mainly in Europe and Asia). Control is based on early diagnosis and the implementation of strict sanitary measures that have not been sufficient until now to stop the disease. ASF is spreading widely worldwide. There are no commercial vaccines or effective treatments available.
During this period VACDIVA has achieved the following advances:
-The full genome sequences (FGS) of the three vaccine candidates, namely Lv17/WB/Rie1, NH/P68, and ASF/ARRIAH/CV-1, have been determined and analysed in comparison with related virulent isolates, which has allowed to identify specific genome features.
- Several Lv17/WB/Rie1 mutants have been generated, plaque purified and sequenced.
- Several combinations of single point mutations of NH/P68 LAV candidate have shown a convenient level of reduction in the corresponding protein activity, thus being a promising alternative for mutant generation.
- After 50 consecutive passages of ASF/ARRIAH/CV-1 LAV, the mortality rate is still 10% in pig.
- The most accepted bait for the oral delivery of the vaccine has been assessed, also the bait physical stability was studied at different temperatures, humidity and in vitro. As well as the use of the bait in field conditions in hunting areas and farms in Spain.
- In wild boar, the optimal dose of LV17/WP/Rie1 candidate has been defined and cross-protective efficacy and safety has been evaluated, yielding a 100% protective efficacy against Armenia07 challenge.
-The best dosis and route for vaccination with Lv17/WB/Rie1 LAV candidate has been identified for domestic pigs with a protection of 100%.
- In vivo studies in domestic pigs with NH/P68 LAV adapted to a cell line (accepted by EMA regulation for vaccine production) have demonstrated a significant reduction of side effects and 100% protection against genotype II virulent virus.
- A few established cell lines (accepted by EMA) have been identified for large-scale production of live ASFV; growth of ASFV is currently being optimized.
- Live ASFV can be lyophilized without significant titre losses, which could mean that the future ASF vaccine will be in a freeze-dried form.
- Expression of 2 potential target candidates for serological DIVA tests have been identified.
- Vaccination scenarios in the EU were defined based on ASF notifications as well as domestic pig and wild boar population information and several parameters such as habitat, environment, etc).
- The wild boar movement database has been finalized
- Questionnaires on domestic pigs and wild boar developed (launched in March)