Memory T cell proliferative responses and IFN-γ productivity sustain long-lasting efficacy of a Cap-based PCV2 vaccine upon PCV2 natural infection and associated disease

Abstract

Porcine circovirus type 2 (PCV2) vaccination represents an important measure to cope with PCV2 infection; however, data regarding the modulation of the immune cell compartment are still limited, especially under field conditions. This study is aimed at investigating the features of the cellular immune response in conventional piglets induced by vaccination using a capsid (Cap) protein-based PCV2 vaccine compared to unvaccinated animals when exposed to PCV2 natural infection. Immune reactivity was evaluated by quantifying peripheral cell subsets involved in the anti-viral response and characterizing the interferon-gamma (IFN-γ) secreting cell (SC) responsiveness both in vivo and upon in vitro whole PCV2 recall. The vaccination triggered an early and intense IFN-γ secreting cell response and induced the activation of peripheral lymphocytes. The early increase of IFN-γ SC frequencies resulted in a remarkable and transient tendency to increased IFN-γ productivity in vaccinated pigs. In vaccinated animals, soon before the onset of infection occurred 15-16 weeks post-vaccination, the recalled PCV2-specific immune response was characterized by moderate PCV2-specific IFN-γ secreting cell frequencies and augmented productivity together with reactive CD4+CD8+ memory T cells. Conversely, upon infection, unvaccinated animals showed very high frequencies of IFN-γ secreting cells and a tendency to lower productivity, which paralleled with effector CD4–CD8+ cytotoxic cell responsiveness. The study shows that PCV2 vaccination induces a long-lasting immunity sustained by memory T cells and IFN-γ secreting cells that potentially played a role in preventing the onset of infection; the extent and duration of this reactivity can be an important feature for evaluating the protective immunity induced by vaccination.

Influence of repeated porcine circovirus type 2 vaccination on sows’ immune response

“…Conversely, the increased numbers of IFN-γ SCs as well as the reduced CV in the blood at T3 and T4 could be influenced by an undetected infection with PCV-2 during gestation. As demonstrated in previous studies (Martelli and others 2011, 2013, Ferrari and others 2014) in vaccinated animals, soon before the onset of infection the recalled PCV-2-specific immune response is characterised by moderate PCV-2-specific IFN-γ SC frequencies and augmented productivity together with reactive CD4+CD8+ cells (memory T cells). So, after vaccination the number of IFN-γ SCs usually has an increase within two weeks, but, subsequently, it can run with an erratic trend in the blood, frequently at a lower level than the primary activation.…”

Comparison of cytokine profiles in peripheral blood mononuclear cells between piglets born from Porcine circovirus 2 vaccinated and non-vaccinated sows

“…where significantly higher levels of IFN-γ-SCs were observed in piglets from vaccinated sows with regard to the ones from unvaccinated sows after colostrum ingestion. The assessment of IFN-γ-SCs is commonly used to measure the cell-mediated immunity response, mainly for the following reasons: 1) the levels of PCV2 specific IFN-γ-SCs increase after infection and vaccination (Fort et al, 2009;Koinig et al, 2015); in fact, PCV2 vaccination induces a long-lasting immunity sustained by memory T cells and IFNγ secreting cells that might participate in the prevention of PCV2 infection (Ferrari et al, 2014); 2) IFN-γ-SCs are inversely correlated with PCV2 viral loads in serum (Seo et al, 2012a;Seo et al, 2012b); and 3) these T cells are specific for both PCV2 Cap and Rep proteins (Fort et al, 2010). However, to the authors' knowledge, information about general cytokine profiles in piglets after colostrum ingestion is missing in the peerreviewed literature.…”

Porcine circovirus 2 immunology and viral evolution

“…Most notably, B and CD3 + CD4 + CD8+ memory/activated Th lymphocytes are depleted and this depletion is related to the development of PCV2-SD [45]. Both vaccination and infection elicit memory/activated Th cells [44, 46]. These cells are activated, antigen specific T cells and memory cells.…”

“…These cells are activated, antigen specific T cells and memory cells. Antigen specific memory T cells persist long term post-infection/vaccination and are able to expand rapidly after recall antigen recognition, thus being able to prevent PCV2 infection quickly [46]. More specifically, it has been suggested that PCV2 specific IFN-γ/TNF-α co-producing CD4 + cells, which are produced upon vaccination/infection, play a central role in controlling and clearing PCV2 infection [44].…”