Targeted Alteration of Antibody-Based Immunodominance Enhances the Heterosubtypic Immunity of an Experimental PCV2 Vaccine.

Agm Rakibuzzaman,Oleksandr Kolyvushko,Sheela Ramamoorthy,Pablo Piñeyro,Angela Pillatzki,Gagandeep Singh,Estelle Leclerc,Peter Nara

doi:10.3390/vaccines8030506

Agm Rakibuzzaman, Oleksandr Kolyvushko + Show 6 more

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https://doi.org/10.3390/vaccines8030506

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Abstract

Despite the availability of commercial vaccines which can effectively prevent clinical signs, porcine circovirus type 2 (PCV2) continues to remain an economically important swine virus, as strain drift, followed by displacement of new subtypes, occurs periodically. We had previously determined that the early antibody responses to the PCV2 capsid protein in infected pigs map to immunodominant but non-protective, linear B cell epitopes. In this study, two of the previously identified immunodominant epitopes were mutated in the backbone of a PCV2b infectious clone, to rationally restructure the immunogenic capsid protein. The rescued virus was used to immunize 3-week-old weanling piglets, followed by challenge with a virulent heterologous PCV2d strain. As expected, immunodominant antibody responses to the targeted epitopes were abrogated in vaccinated pigs, while a broadening of the virus neutralization responses was detected. Vaccinated pigs were completely protected against challenge viral replication, had reduced microscopic lesions in lymphoid organs and gained significantly more body weight when compared to unvaccinated pigs. Thus, the experimental PCV2 vaccine developed was highly effective against challenge, and, if adopted commercially, can potentially slow down or eliminate new strain creation.

Highlights

Porcine circovirus type 2 (PCV2) is a small, single-stranded DNA virus which belongs to the circoviridae family
Using sequential anti-sera collected from infected pigs, and a panel of overlapping peptides spanning the PCV2 capsid protein, we identified three new linear immunodominant—but non-protective—regions of the PCV2 capsid protein [7]
In this study we explored the hypothesis that alteration of the immunodominance properties of the PCV2 capsid protein will enhance rational vaccine design and result in significant protection against challenge

Summary

Introduction

Porcine circovirus type 2 (PCV2) is a small, single-stranded DNA virus which belongs to the circoviridae family. It is an economically important swine virus which causes post-weaning multi-systemic wasting syndrome (PMWS) and lymphadenopathy in weanling piglets, along with a range of clinical signs including jaundice, nephropathy, reproductive and respiratory disorders, collectively known as porcine circovirus associated diseases or PCVAD [1]. Several commercial vaccines against PCV2 are available and commonly deployed in the field. They are very effective in preventing clinical signs of PCV2 and in reducing economic losses associated with PCV2 infection.

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