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BIONÆR-Bionæringsprogram

ICRAD Novel Strategies to enhance vaccine immunity in neonatal livestock.

Alternative title: Neonatal livestock vaccines.

Awarded: NOK 3.2 mill.

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 by far to prevent, manage and even eradicate diseases. Most vaccines provide protection by inducing antibodies, which can be transferred to the offspring through the placenta or through colostrum early after birth. Such maternally derived antibodies (MDA) play a critical role in protecting new-born livestock against infectious diseases during their early life. However, MDA can also dampen immune responses of neonates to vaccination by neutralizing the vaccine before the animals induce an immune response. Thus, as MDA wanes immunised animals remain vulnerable to pathogen challenge. In this project, we will test a DNA vaccine strategy designed to enhance immune responses in neonatal animals with MDA. We will focus on porcine reproductive and respiratory syndrome virus (PRRSV) in pigs. PRRSV is considered the most economically important disease affecting the global pig industry with estimated losses in Europe exceeding ?1.5 billion p.a. MDA interfere with neonatal vaccination against PPRSV leading to high vulnerability at the time of weaning or feedlot/fattening where MDA are low and active immunity is not yet in place. We have generated vaccines where PRRSV antigens are specifically delivered to dendritic cell (DC) as a method to enhance immunogenicity. We will then test if a targeted vaccine prime followed by a modified live vaccine (MLV) boost strategy enhances cell mediated and antibody responses and increase vaccine efficacy in MDA+ piglets. Complementary, in vitro experiments will be conducted using the same DC targeted vaccines to better understand how they counteract the negative effect of MDA on the immune responses.

Infectious diseases of livestock continue to cause a major financial impact globally, threatening food security and public health. Disease control measures comprise a combination of biosecurity with both preventative and therapeutic treatments. However, vaccination remains the most cost-effective tool by far 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, including the neutralisation of live attenuated vaccines and the inhibition of neonatal B cell responses. Thus, as MDA wanes immunised animals remain vulnerable to pathogen challenge. In this project, we will test a DNA vaccine strategy designed to enhance immune responses in neonatal animals with MDA. We will focus on porcine reproductive and respiratory syndrome virus (PRRSV) in pigs, for which the applicants have developed preliminary tools to counteract different mechanisms of MDA interference. PRRSV is considered the most economically important disease affecting the global pig industry with estimated losses in Europe exceeding €1.5 billion p.a. MDA interfere with neonatal vaccination against PPRSV leading to high vulnerability at the time of weaning or feedlot/fattening where MDA are low and active immunity is not yet in place. We will generate DNA vaccines where PRRSV antigens are fused to XCL1 or anti-MHC-II scFv, as dendritic cell (DC) targeting moieties that we have shown enhance immunogenicity. We will then test if a targeted DNA prime/modified live vaccine (MLV) boost vaccine strategy enhances cell mediated and antibody responses and increase vaccine efficacy in MDA+ piglets. Complementary in vitro experiments will be conducted using DC targeted antigens to understand how they counteract the MDA-negative effect on B-cell responses.

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BIONÆR-Bionæringsprogram