Antibody response against koala retrovirus (KoRV) in koalas harboring KoRV-A in the presence or absence of KoRV-B

Abstract

Koala retrovirus (KoRV) is in the process of endogenization into the koala ( Phascolarctos cinereus ) genome and is currently spreading through the Australian koala population. Understanding how the koala’s immune system responds to KoRV infection is critical for developing an efficacious vaccine to protect koalas. To this end, we analyzed the antibody response of 235 wild koalas, sampled longitudinally over a four-year period, that harbored KoRV-A, and with or without KoRV-B. We found that the majority of the sampled koalas were able to make anti-KoRV antibodies, and that there was a linear increase in anti-KoRV IgG levels in koalas up to approximately seven years of age and then a gradual decrease thereafter. Koalas infected with both KoRV-A and KoRV-B were found to have slightly higher anti-KoRV IgG titers than koalas with KoRV-A alone and there was an inverse relationship between anti-KoRV IgG levels and circulating KoRV viral load. Finally, we identified distinct epitopes on the KoRV envelope protein that were recognized by antibodies. Together, these findings provide insight into the koala’s immune response to KoRV and may be useful in the development of a therapeutic KoRV vaccine.

Therapeutic vaccination of koalas harbouring endogenous koala retrovirus (KoRV) improves antibody responses and reduces circulating viral load

“…Ten captive northern koalas (endogenously infected with KoRV-A) were vaccinated subcutaneously with two doses of the vaccine. Prior to vaccination, we detected anti-KoRV IgG titres that were similar to levels previously reported in wild koalas harbouring endogenous KoRV 14 . Following vaccination, all animals had significant increases in total anti-KoRV IgG levels, ranging from a 2–37 fold increase by week 8 (Fig.…”

“…Recent studies suggest that KoRV-A sits at an intersection between a fully endogenized retrovirus and an exogenous retrovirus through its ability to produce infectious particles in the koala 19 . KoRV-A-directed immune response in natural infection has also been previously established, thus confirming the possibility for vaccine development 14 . Similar to observations from our current study, ongoing studies in humans have shown that HERV-K-directed immune responses can serve as a basis for vaccine development against HERV-K-associated cancers 20 , 21 .…”

“…We recently showed that naturally infected koalas harbouring endogenous KoRV make anti-KoRV antibodies 14 . In the current study, we evaluated whether a recombinant KoRV Env protein vaccine was able to induce anti-KoRV antibodies in koalas harbouring endogenous KoRV.…”

“…We previously showed that koalas harbouring endogenous KoRV are not tolerant to the KoRV but rather make antibodies against distinct regions on the KoRV Env protein 14 . This highlighted the possibility of developing a therapeutic vaccine to boost natural immunity.…”

Koala retrovirus epidemiology, transmission mode, pathogenesis, and host immune response in koalas (Phascolarctos cinereus): a review

“…In a study with 16 koalas, Fiebig et al observed that koalas did not produce antibodies against KoRV-A [55], but in a recent study using 235 koalas, Quigley et al analyzed the antibody response and found that most koalas produced anti-KoRV antibodies [56]. This finding is very important for developing a therapeutic KoRV vaccine.…”