Vaccination against the Koala Retrovirus (KoRV): Problems and Strategies.

Joachim Denner

doi:10.3390/ani11123555

Abstract

Simple SummaryThe koala population is declining in northern Australia, and a major reason for this is the infection of the immunosuppressive koala retrovirus (KoRV), which is endogenous in many animals. This endogenous virus and its exogenous forms may induce lymphomas and immunodeficiency associated with opportunistic infections, including chlamydia infections. To generate a vaccine, we produced the recombinant surface and transmembrane envelope proteins of the KoRV and immunized goats, rats and mice. In all cases, we obtained antibodies which were able to neutralize the KoRV and recognize defined epitopes in the envelope proteins. However, we and others observed that koalas carrying the endogenous KoRV are tolerant, e.g., are unable to induce an immune response to the virus. Nevertheless, we propose that KoRV-negative animals will produce an antiviral immune response and will be protected when immunized with such a vaccine. This immunization will also reduce the number and severity of opportunistic infections because there is no KoRV-induced immunosuppression.The koala retrovirus (KoRV) is spreading in the koala population from the north to the south of Australia and is also in the process of endogenization into the koala genome. Virus infection is associated with tumorigenesis and immunodeficiency and is contributing to the decline of the animal population. Antibody production is an excellent marker of retrovirus infection; however, animals carrying endogenous KoRV are tolerant. Therefore, the therapeutic immunization of animals carrying endogenous KoRV seems to be ineffective. Using the recombinant transmembrane (TM) envelope protein of the KoRV, we immunized goats, rats and mice, obtaining in all cases neutralizing antibodies which recognize epitopes in the fusion peptide proximal region (FPPR), and in the membrane-proximal external region (MPER). Immunizing several animal species with the corresponding TM envelope protein of the closely related porcine endogenous retrovirus (PERV), as well as the feline leukemia virus (FeLV), we also induced neutralizing antibodies with similar epitopes. Immunizing with the TM envelope protein in addition to the surface envelope proteins of all three viruses resulted in higher titers of neutralizing antibodies. Immunizing KoRV-negative koalas with our vaccine (which is composed of both envelope proteins) may protect these animals from infection, and these may be the starting points of a virus-free population.

Highlights

For Western blot analyses, lysates from purified viruses or recombinant envelope proteins were used, and we showed that the sera did not neutralize koala retrovirus (KoRV) [48]
Our study [48] and the study conducted by Joyce et al [56] both indicate that koalas which have the endogenous KoRV in their genome do not produce antibodies against the virus because they are tolerant
This suggests that additional immunization will be unable to produce binding and neutralizing antibodies able to reduce the virus load of these animals. This is supported by the finding that therapeutic vaccination was inefficient in clinically healthy cats persistently infected with feline leukemia virus (FeLV) [57]

Summary

Introduction

MuLV, FeLV and GaLV induce leukemia and immunodeficiency in the infected hosts. HIV-1 infections in humans are more often associated with Pneumocystis jirovecii, Candida albicans, and Toxoplasma gondii infections. It is unclear why chlamydia infections are the most common among KoRV-positive animals. Most retroviruses, including HIV-1, FeLV and MuLV, are immunosuppressive viruses, and the immunosuppressive activity of KoRV was demonstrated by opportunistic infections, and by alterations of the cytokine release in the infected animals. It is important to note that in the case of FeLV, more cats die from opportunistic infections based on the virus-induced immunosuppression than from leukemia [2,27,28]. Whereas in the case of the related PERV its origin from retroviral sequences in lesser Egyptian jerboas, rock hyraxes and murid species is well characterized [30], the origin of the KoRV is still unclear; it is possibly a transspecies transmission from rodents or bats [31,32]

Immunization Experiments with KoRV Envelope Proteins

C Epitopes

B Antige

Screening of KoRV-Positive Animals for Neutralizing Antibodies

Immunization Experiments In Vivo

Conclusions and Outlook