Passive Immunisation against RHDV2 Induces Protection against Disease but Not Infection

Robyn N Hall,Tiffany W O’Connor,Andrew J Read,Melissa Piper,Tegan King,Tanja Strive,Sylvia Vrankovic

doi:10.3390/vaccines9101197

Abstract

Rabbit haemorrhagic disease virus 2 (RHDV2) is a lagovirus in the family Caliciviridae. The closely related Rabbit haemorrhagic disease virus (RHDV, termed RHDV1 throughout this manuscript for clarity) has been used extensively as a biocontrol agent in Australia since the mid-1990s to manage wild rabbit populations, a major economic and environmental pest species. Releasing RHDV1 into populations with a high proportion of rabbits less than 8–10 weeks of age leads to non-lethal infection in many of these young animals, with subsequent seroconversion and long-term immunity against reinfection. In contrast, RHDV2 causes lethal disease even in young rabbits, potentially offering substantial benefits for rabbit management programs over RHDV1. However, it is not clear how acquired resistance from maternal antibodies may influence immunity after RHDV2 infection. In this study, we assessed serological responses after RHDV2 challenge in young rabbits of three different ages (5-, 7-, or 9-weeks-old) that were passively immunised with either high- (titre of 2560 by RHDV IgG ELISA; 2.41 mg/mL total protein) or low- (titre of 160–640 by RHDV IgG ELISA; 1.41 mg/mL total protein) dose RHDV2 IgG to simulate maternal antibodies. All rabbits treated with a high dose and 75% of those treated with a low dose of RHDV2 IgG survived virus challenge. Surviving animals developed robust lagovirus-specific IgA, IgM, and IgG responses within 10 days post infection. These findings demonstrate that the protection against RHDV2 conferred by passive immunisation is not sterilising. Correspondingly, this suggests that the presence of maternal antibodies in wild rabbit populations may impede the effectiveness of RHDV2 as a biocontrol.

Highlights

Two lagoviruses are known to be pathogenic in European rabbits (Oryctolagus cuniculus)—RHDV1 and Rabbit haemorrhagic disease virus 2 (RHDV2) [1]
RHDV2 IgG was purified from hyperimmune rabbit serum using fast protein liquid chromatography (FPLC), dialysed against PBS, and filter sterilised
We hypothesised that passive immunisation against RHDV2, representative of maternal antibodies, would prevent both disease and infection after virus challenge

Summary

Introduction

Two lagoviruses are known to be pathogenic in European rabbits (Oryctolagus cuniculus)—RHDV1 (genotype GI.1) and RHDV2 (genotype GI.2) [1]. While young animals may become infected, intrinsic age-dependent resistance to lethal disease with these variants leads to many surviving and acquiring life-long immunity against reinfection [14,15]. The mechanism underlying this innate resistance to RHDV1 in young rabbits is not fully understood, but it is known to be independent of maternal antibody status [16], can be abrogated by immunosuppression [17], and correlates with constitutively heightened innate immune responses, those associated with major histocompatibility class II molecules, natural killer cells, macrophages, and cholangiocytes [18,19]

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