21-ICRAD - Novel strategies to enhance vaccine immunity in neonatal livestock (NEOVACC)

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Infectious diseases of livestock continue to cause a major financial impact globally, threatening food security and public health. Vaccination remains the most cost-effective tool to prevent, manage and even eradicate diseases. Maternally derived antibodies (MDA) play a critical role in protecting neonatal livestock against infectious diseases during their early life. However, MDA can dampen immune responses of neonates to vaccination through a number of distinct mechanisms. Thus, as MDA wanes immunised animals remain vulnerable to pathogen challenge. In this project, we will test vaccine strategies designed to enhance immune responses in neonatal animals with MDA. Our state-of-the-art approaches to this challenge span improved immunogen design, antigen delivery configuration and immunopotentiators. We will focus on two major endemic viral diseases: bovine respiratory syncytial virus (BRSV) in cattle and porcine reproductive and respiratory syndrome virus (PRRSV) in pigs, for which the consortium has developed preliminary tools and knowledge of strategies to counteract different mechanisms of MDA interference. The project is structured with three complementary work-packages that aim to: (1) Design BSRV immunogens to exploit differences in antibody repertoires between adult and neonatal cattle; (2) Evaluate a DNA vaccine-based approach against PRRSV designed to counteract MDA interference; and (3) Engineer peptide-based immune checkpoint inhibitors into live PRRSV vaccines to enhance neonatal responses to vaccination. The outputs from this project will directly benefit the development of improved vaccines against these two key diseases but also as a concept since the approaches may be exploited in the context of other pathogens, livestock species and humans.