4 Adaptive immune response against PRRS virus

Humoral response against PRRS virus:

Circulating antibodies against PRRS virus can be detected in some pigs as soon as 5-9 days post-infection (PI). Usually, all animals seroconvert by the second-third week PI.

During the primary response, IgM are predominant and can be detected until 42 days PI.

By the second week, IgG appear and peak around three to six weeks and persist for months. Although nsp7 and GP3, GP5 and M could be involved in the development of antibodies, most of them are directed against N protein and nsp1 and 2.

This rapid humoral response is devoid of neutralising capacity.

It is important to note that most diagnostic tests detect antibodies against N protein; as we have seen, these antibodies appear early and persist for months, but are non-neutralizing and do not correlate with protection.

Indeed, it has been demonstrated in vitro and in vivo that non-neutralising antibodies enhance viral replication in alveolar macrophages, a phenomenon known as antibody-dependent enhancement (ADE) -in which antibodies act as a Trojan horse for PRRS virus, facilitating the internalisation of the viral particles into macrophages- .

However, the real importance in PRRS virus pathogenesis of such a phenomenon is unclear since ADE detection has not been successfully achieved by among laboratories.

Neutralising antibodies (NAs) can be detected around one month or even later, rarely being detected before that. Nevertheless, titres of NAs against PRRS virus are usually low (below 1:32) or almost nil.

Several viral targets for NAs have been reported, among them GP2a, GP3, GP4, GP5 and M protein.

In the past, it was widely accepted that GP5 contained the main neutralisation epitope; however, recent studies have questioned this assumption. Knocking out CD163 in pigs is sufficient to render animals non-susceptible to PRRSV, demonstrating that this receptor is necessary for viral infection and replication; thus, it is reasonable to expect that regions in GP2, GP3 and GP4 –that interact with CD163– would be the principal candidates to contain the main neutralisation epitopes.

Titres of neutralising antibodies vary according to PRRS virus isolates, and even some strains do not induce NA at all. Also, titres vary among pigs inoculated with the same strain.

Cell-mediated immunity against PRRS virus:

It has been demonstrated that cell-mediated immunity against PRRS virus is unusual, low and delayed.

Firstly, proliferative responses against PRRS virus appear late, at 4 weeks PI.

Secondly, PRRS virus-specific cytotoxic T lymphocytes are very weak and slow to develop. Indeed, some authors have shown that when cytotoxic T lymphocytes appear, they do not display cytotoxic activity, probably due to a defect in the recognition of infected cells, some blocking of the cytotoxic mechanisms, or because the cytotoxic T lymphocytes detected are not virus-specific.

Thirdly, several studies using IFN-γ ELISPOT for measuring cell-mediated immunity have shown that PRRS virus-specific IFN-γ-secreting cells (IFN-γ-SC) develop after 2-3 weeks PI. Later, the development is erratic for several weeks, thereafter increasing slowly.

Compared to other common pig viruses, PRRS virus-specific IFN-γ-SC frequencies after infection or vaccination are 3-4 times lower.

Cell-mediated immunity also varies according to PRRS virus isolates. Several viral targets for cell-mediated immunity have been demonstrated; among them, nsp1, nsp2, nsp5, nsp7, nsp9, nsp11, GP3, GP4, GP5, M and N.

The genetic background of the host may also influence both NA production and cell-mediated immunity.