Passive Immunisation against RHDV2 Induces Protection against Disease but Not Infection

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.

Immunological Cross-Protection between Different Rabbit Hemorrhagic Disease Viruses—Implications for Rabbit Biocontrol and Vaccine Development

“…GI.2 can cause disease in younger rabbits from four weeks of age, and the pathogenicity of Australian GI.2 variants is close to 100% in susceptible animals [ 20 ]. However, young rabbits with GI.2 maternally derived immunity are resistant to disease with GI.2 [ 21 , 35 ]. Experimental work using passively immunised kittens, to mimic the presence of maternal antibodies, demonstrated a robust antibody response after virus challenge [ 21 ].…”

“…Initially, a dose of 50 RID 50 was selected as the challenge dose for rabbits with experimentally or naturally acquired immunity. This was based on an estimate of the amount of RHDV a rabbit may be exposed to during a control program [ 21 ]. However, to assess whether responses were dose dependent, in other experiments, this was increased to 150 RID 50 (low dose in Figure 1 C) or 1500 RID 50 (high dose in Figure 1 C).…”

Rabbit Haemorrhagic Disease Virus 2 (RHDV2; GI.2) in Ireland Focusing on Wild Irish Hares (Lepus timidus hibernicus): An Overview of the First Outbreaks and Contextual Review

“…Mean mortality rates of 70–90% for RHDV1 and 5–70% for RHDV2 have been reported [ 33 ]. At least some of the variation in the reported mortality rates for RHDV2 may be related to host age and infectious dose [ 29 ]. However, recent experimental work suggests that the case fatality rate can reach 100% in rabbits [ 20 , 32 ].…”

“…There are few detailed pathology studies specifically on RHDV2 [ 13 , 20 , 27 , 28 , 29 ], but in many aspects, disease progression resembles that induced by RHDV1 (in rabbits; [ 13 ]) and EBHSV (in hares; [ 8 , 11 , 27 , 30 ]. Infected animals develop fever (pyrexia), and antemortem clinical signs can also include anorexia, collapse, lethargy, seizures, icterus, bleeding from the mouth, dyspnoea, hypothermia, bradycardia, or poor blood clotting [ 28 ].…”

“…For example, Mahar et al [ 57 ] reported at least six viable recombination events in a two-year period since the discovery of RHDV2 in mid-2015 in Australia [ 57 , 60 ]. However, recent experimental work from Australia suggests that in rabbits, the presence of maternal antibodies, from surviving exposed does to their kits, could provide protection from disease [ 29 ]. From the Australian perspective, this could impact RHDV2 as a biocontrol agent, but could have more beneficial interpretation elsewhere, where a reduction in disease-induced mortalities would be welcomed.…”