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Characterizing the Cellular Immune Response to Parainfluenza Virus 3.

ABSTRACT: Parainfluenza virus type 3 (PIV3) infections are a major cause of morbidity and mortality in immunocompromised individuals, with no approved therapies. Our group has demonstrated the safety and efficacy of adoptively transferred virus-specific T cells for the prevention and treatment of a broad range of viral infections including BK virus, cytomegalovirus, adenovirus, human herpesvirus 6, and Epstein-Barr virus. However, this approach is restricted to well-characterized viruses with known immunogenic/protective T-cell target antigens, precluding extension to PIV3. We now characterize the cellular immune response to all 7 PIV3-encoded antigens in 17 healthy donors and define a hierarchy of immunogenicity based on the frequency of responding donors and the magnitude of specific cells. We show that reactive populations of both CD4+ and CD8+ T cells are capable of producing Th1-polarized effector cytokines and killing PIV3-expressing targets. Furthermore, we confirm the clinical relevance of these cells by demonstrating a direct correlation between the presence of PIV3-specific T cells and viral control in allogeneic hematopoietic stem cell transplant recipients. Taken together, our findings support the clinical use of PIV3-specific T cells produced with our Good Manufacturing Practice-compliant manufacturing process, in immunocompromised patients with uncontrolled infections.

SUBMITTER: Aguayo-Hiraldo PI

PROVIDER: S-EPMC5853958 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Bovine parainfluenza type 3 (BPIV3) and bovine respiratory syncytial virus (BRSV) may cause bovine respiratory disease (BRD) in very young calves, and therefore vaccination should induce protection at the youngest age and as quickly as possible. This can be achieved by intranasal vaccination with a vaccine containing live attenuated BRSV and BPIV3 virus strains. The objective of this study was to measure gene expression levels by means of RT-qPCR of proteins involved in the innate and adaptive immune response in the nasopharyngeal mucosae after administration of the above-mentioned vaccine and after challenge with BPIV3. Gene expression profiles were different between (i) vaccinated, (ii) nonvaccinated-challenged, and (iii) vaccinated-challenged animals. In nonvaccinated-challenged animals, expression of genes involved in development of disease symptoms and pathology were increased, however, this was not the case after vaccination. Moreover, gene expression patterns of vaccinated animals reflected induction of the antiviral and innate immune pathways as well as an initial Th1 (cytotoxic) cellular response. After challenge with BPIV3, the vaccinated animals were protected against nasal shedding of the challenge virus and clinical symptoms, and in parallel the expression levels of the investigated genes had returned to values that were found before vaccination. In conclusion, in comparison to the virulent wild-type field isolates, the two virus strains in the vaccine have lost their capacity to evade the immune response, resulting in the induction of an antiviral state followed by a very early activation of innate immune and antiviral responses as well as induction of specific cellular immune pathways, resulting in protection. The exact changes in the genomes of these vaccine strains leading to attenuation have not been identified. These data represent the real-life situation and can serve as a basis for further detailed research. This is the first report describing the effects on immune gene expression profiles in the nasal mucosae induced by intranasal vaccination with a bivalent, live BRSV-BPI3V vaccine formulation in comparison to wild-type infection with a virulent BPI3V strain.

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Characterizing the Cellular Immune Response to Parainfluenza Virus 3.

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