Prospects of Next-Generation Vaccines for Bluetongue

Abstract

Bluetongue (BT) is a haemorrhagic disease of wild and domestic ruminants with a huge economic worldwide impact on livestock. The disease is caused by BT-virus transmitted by Culicoides biting midges and disease control without vaccination is hardly possible. Vaccination is the most feasible and cost-effective way to minimize economic losses. Marketed BT vaccines are successfully used in different parts of the world. Inactivated BT vaccines are efficacious and safe but relatively expensive, whereas live-attenuated vaccines are efficacious and cheap but are unsafe because of under-attenuation, onward spread, reversion to virulence, and reassortment events. Both manufactured BT vaccines do not enable differentiating infected from vaccinated animals (DIVA) and protection is limited to the respective serotype. The ideal BT vaccine is a licensed, affordable, completely safe DIVA vaccine, that induces quick, lifelong, broad protection in all susceptible ruminant species. Promising vaccine candidates show improvement for one or more of these main vaccine standards. BTV protein vaccines and viral vector vaccines have DIVA potential depending on the selected BTV antigens, but are less effective and likely more costly per protected animal than current vaccines. Several vaccine platforms based on replicating BTV are applied for many serotypes by exchange of serotype dominant outer shell proteins. These platforms based on one BTV backbone result in attenuation or abortive virus replication and prevent disease by and spread of vaccine virus as well as reversion to virulence. These replicating BT vaccines induce humoral and T-cell mediated immune responses to all viral proteins except to one, which could enable DIVA tests. Most of these replicating vaccines can be produced similarly as currently marketed BT vaccines. All replicating vaccine platforms developed by reverse genetics are classified as genetic modified organisms. This implies extensive and expensive safety trails in target ruminant species, and acceptance by the community could be hindered. Nonetheless, several experimental BT vaccines show very promising improvements and could compete with marketed vaccines regarding their vaccine profile, but none of these next generation BT vaccines have been licensed yet.

Heterologous Combination of ChAdOx1 and MVA Vectors Expressing Protein NS1 as Vaccination Strategy to Induce Durable and Cross-Protective CD8+ T Cell Immunity to Bluetongue Virus

“…Several experimental BTV vaccines are under development in order to improve the marketed vaccines and overcome their disadvantages. Among the different types of vaccines under development, those based on viral vectors expressing one or more BTV proteins and vaccines based on attenuation of BTV by reverse genetics (e.g., disabled infectious single cycle (DISC) and disabled infectious single animal (DISA) vaccines) [ 15 , 69 , 70 ] stand out. These vaccines are effective, safe, make possible a DIVA strategy, but they do not elicit multiserotype protection, even though application of DISC and DISA vaccines for multiple serotypes have been successfully studied in ruminants.…”

“…Additionally, these vaccines target mostly protein VP2, which represents the main inductor of neutralizing antibodies but has a highly variable antigen sequence among serotypes (up to 72.9% aa divergence) [ 12 ]. These conventional vaccines have been useful to control or limit BTV expansion so far, but they are not suitable for cross-protection between serotypes and do not permit the differentiation between infected and vaccinated animals (DIVA strategy) [ 14 , 15 ]. Non-structural proteins have been found to play a key role in several aspects of the infection such as virulence and replication and have therefore been studied as targets for antiviral therapies [ 16 , 17 ].…”

An updated review on bluetongue virus: epidemiology, pathobiology, and advances in diagnosis and control with special reference to India

“… 2018 ). Continuous screening of different serotypes and topotypes of BTV are important for epidemiological monitoring and important for the effective implementation of control and eradication strategies including vaccine matching (van Rijn 2019 ).…”

“… 2014 ; Feenstra and van Rijn 2017 ; Ranjan et al. 2019 ; van Rijn 2019 ). Prophylactic vaccination has contributed to BT control and significantly reduced the economic losses caused by morbidity, mortality, reproductive problems, and reduced milk production (Kutzler and Weiner 2008 ; Pioz et al.…”

“… 2014 ; McVey and MacLachlan 2015 ; Feenstra and van Rijn 2017 ; Mayo et al. 2017 ; van Rijn 2019 ). The pentavalent inactivated adjuvanted vaccine containing BTV-1, -2, -10, -16 and -23 has been used for the control of BT in India (Reddy et al.…”