Anti-idiotypic antibodies reduce efficacy of the attenuated vaccine against highly pathogenic PRRSV challenge

Abstract

Background: The inability of current vaccines to provide effective protection against porcine reproductive and respiratory syndrome virus (PRRSV) infection is not fully understood. One of the reasons might be the presence of anti-idiotypic antibodies (Ab2s) to the envelope glycoprotein GP5 induced by PRRSV infection since our previous studies demonstrated the presence of auto-Ab2s (aAb2s) in pigs infected with PRRSV. To test this hypothesis, PRRSV negative piglets were injected with a monoclonal Ab2 (Mab2-5G2) and aAb2s that are specific for anti-GP5 antibody, vaccinated with the attenuated PRRSV vaccine CH-1R and then challenged with the highly pathogenic PRRSV HuN4 strain. The animals were evaluated for clinical signs, pathological changes of the thymus and lungs, viremia, levels of serum antibodies and cytokines.

Results: The piglets injected with Mab2-5G2 or aAb2, and who received the attenuated PRRSV vaccine CH-1R before challenge, produced high levels of anti-N antibodies, IL-2 and IL-4, but low levels of neutralizing antibodies. After PRRSV HuN4 challenge, the animals showed obvious clinical signs, including lung lesions, severe thymus atrophy and decreased production of IL-4 and higher level of viremia.

Conclusion: When anti-GP5 Ab2s are present, the use of attenuated PRRSV vaccine CH-1R against HP-PRRSV infection is not recommended. It can result in poor health status with pneumonia and thymus atrophy.

Figure 1

Rectal temperature (°C) changes in piglets after HP-PRRSV infection. Group 1 to 4 piglets were given Mab2-5G2, aAb2s, 7H12 and normal swine IgG on 0 DPI, respectively, vaccinated on 14 and 28 DPI and challenged with HP-PRRSV on 0 DPC. Group 5 piglets were challenged with HP-PRRSV only and Group 6 piglets received PBS. Each point represents the mean (±S.D) generated from all piglets in each group on each DPC.

Figure 2

Gross pathology of thymus on 28 DPC. Thymus of a piglet from Group 1 (A), Group 2 (B) and Group 5 (E) showed serious atrophy. Thymus of a piglet from Group 3 (C) and Group 4 (D) showed slight atrophy and thymus of an age-matched control piglet from Group 6 (F) was normal.

Figure 3

Pathological examinations of the thymus and lung on 28 DPC. Thymus of a piglet from Group 1 (A), Group 2 (B), and Group 5 (E) showed blurred boundaries between the thymus cortex and medulla. Thymus of a piglet from Group 3 (C), Group 4 (D) and Group 6 (F) showed no microscopic lesions (magnification × 50). Lungs of a piglet from Group 1 (G), Group 2 (H) and Group 5 (K) showed interstitial pneumonia lesions, lungs of a piglet from Group 3 (I) and Group 4 (J) showed mild interstitial pneumonia, and a Group 6 piglet (L) was normal (magnification × 200).

Figure 4

Serum levels of cytokines. Serum concentrations of IFN-γ (A), IL-2 (B), IL-4 (C) and IL-10 (D) were measured using the commercial ELISA kits (Market Inc, USA). Each point represents the mean value (±S.D) generated from six groups of piglets on different DPIs or DPCs.

Figure 5

Levels of serum antibodies. Anti-N antibodies were detected using the HerdCheck® PRRS ELISA kit with the cutoff value of S/P ratio of 0.4 (A) and anti-GP2/GP5 antibodies were detected using the LIVTESTSUISPRRS A/S® kit with the relative index (expressed as a percentage) greater than 20 as positive (B). Each point represents the mean (±S.D.) generated from six groups of piglets on different DPIs or DPCs.