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

Abstract

The long-term survival of the koala is under serious threat from multiple factors, including infectious disease agents such as Chlamydia and koala retrovirus (KoRV). KoRV is present in both exogenous and endogenous forms, depending on the geographical location of the population. In the northern half of Australia, it is present as an endogenous infection in all koalas, making a case for an urgent need to develop a therapeutic vaccine that might prevent KoRV-associated pathologies in these koalas. To this end, we determined the therapeutic effects of vaccinating koalas harbouring endogenous KoRV with a recombinant KoRV Env protein combined with a Tri-adjuvant. We found that vaccination led to a significant increase in circulating anti-KoRV IgG levels, as well as increase in neutralising antibodies. Our study also showed that post-vaccination antibodies were able to recognize epitopes on the Env protein that were unrecognised pre-vaccination, as well as resulting in an increase in the recognition of the previously recognised epitopes. The vaccine also induced antibodies that were cross-reactive against multiple KoRV-subtypes. Finally, we found a complete clearance of KoRV-A in plasma from koalas that had detectable levels of KoRV-A pre-vaccination. Similarly, there was a significant reduction in the expression of KoRV-B viral RNA levels post-vaccination. Collectively, this study showed that koalas harbouring endogenous KoRV can benefit from prophylactic vaccination against KoRV using a recombinant KoRV-A Env protein and that the mechanism of this protection might be through the boosting of natural anti-KoRV antibodies and expanding the breadth of the recognised epitopes.

Concerns regarding vaccination as a management strategy against koala retrovirus

“…As well as the recombinant E. coli expressed Env protein ELISA, Olagoke, et al [1][2][3] also use a peptide specific ELISA. The authors report various peptide displayed fluorescence intensities above background, however it is not clear from the reported methods exactly how background was calculated.…”

Toll-Like Receptor Expression Profiles in Koala (Phascolarctos cinereus) Peripheral Blood Mononuclear Cells Infected with Multiple KoRV Subtypes

“…It is now widely believed that PRRs of the innate immune system, particularly TLRs, are involved in modulating and shaping humoral and cellular immune responses [ 41 ]. At present, no licensed KoRV vaccine is available; however, researchers are working on KoRV vaccine development [ 21 , 42 , 43 , 44 , 45 , 46 ]. A proper understanding of koala’s immune response against KoRV is a key step in therapeutic and prophylactic interventions for better conservation and management strategies to protect koalas.…”

“…In a recent study, a recombinant envelope protein-based KoRV vaccine was found to elicit anti-KoRV IgG and decreased viral loads in vaccinated koalas [ 43 ]. In a subsequent study by the same group, a recombinant KoRV Env protein vaccine combined with a Tri-adjuvant was found to significantly increase circulating neutralizing anti-KoRV IgG antibodies, with cross-reactivity against multiple KoRV-subtypes [ 45 ]. However, Fiebig et al, in a previous study with a limited number of koala populations, observed a lack of antibody response against KoRV infection [ 37 ].…”

Koalas vaccinated against Koala retrovirus respond by producing increased levels of interferon-gamma

“…IFN-γ has also been linked to B-cell differentiation into IgG production [ 9 ]. The increase in IFN-γ detected in this work may offer insight into the sustained anti-KoRV IgG production and reduction in viral load reported in koalas following vaccination [ 7 ]. A possible mechanism for the observed increase in IFN-γ levels post-vaccination may be the inclusion of Poly[di(sodium carboxylatoethylphenoxy)phosphazene] (PCEP) as an adjuvant component in the KoRV vaccine.…”

“…KoRV has also been linked to increased susceptibility to diseases in koalas [ 6 ]. We recently described antibody production and reduction in viral load following vaccination in koalas harbouring endogenous KoRV [ 7 ]. Briefly, koalas were vaccinated with a recombinant KoRV Env protein along with a Tri-adjuvant of poly I:C, polyphosphazine and host defence peptide 1002.…”