Induction of Neutralizing Antibody Response Against Koala Retrovirus (KoRV) and Reduction in Viral Load in Koalas Following Vaccination with Recombinant KoRV Envelope Protein

Overview

Journal NPJ Vaccines

Date 2018 Aug 8

PMID 30083396

Citations 15

Authors

O Olagoke

D Miller

F Hemmatzadeh

T Stephenson

J Fabijan

P Hutt

S Finch

N Speight

P Timms

Affiliations

Soon will be listed here.

Abstract

Koala retrovirus (KoRV) infects the majority of Australia's koalas () and has been linked to several life-threatening diseases such as lymphoma and leukemia, as well as and thus poses a threat to the continued survival of this species. While quarantine and antiretroviral drug treatment are possible control measures, they are impractical, leaving vaccination as the only realistic option. In this study, we examined the effect of a recombinant envelope protein-based anti-KoRV vaccine in two groups of South Australian koalas: KoRV infected or KoRV free. We report a successful vaccination response in the koalas with no vaccine-associated side effects. The vaccine induced a significant humoral immune response as well as the production of neutralizing antibodies in both groups of koalas. We also identified B-cell epitopes that were differentially recognized in KoRV-infected versus KoRV-free koalas following vaccination. Importantly, we also showed that vaccination had a therapeutic effect on koalas infected exogenously with KoRV by reducing their circulating viral load. Together, this study highlights the possibility of successfully developing a vaccine against KoRV infection in koalas.

Citing Articles

Reduction of and Koala Retrovirus subtype B expression in wild koalas vaccinated with novel peptide and peptide/recombinant protein formulations.

Quigley B, Timms P, Nyari S, McKay P, Hanger J, Phillips S Vaccine X. 2023; 14:100329.

PMID: 37577264 PMC: 10422670. DOI: 10.1016/j.jvacx.2023.100329.

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

Denner J Animals (Basel). 2021; 11(12).

PMID: 34944329 PMC: 8697897. DOI: 10.3390/ani11123555.

Koala retrovirus genetic diversity and transmission dynamics within captive koala populations.

Joyce B, Blyton M, Johnston S, Young P, Chappell K Proc Natl Acad Sci U S A. 2021; 118(38).

PMID: 34493581 PMC: 8463891. DOI: 10.1073/pnas.2024021118.

Molecular Diagnosis of Koala Retrovirus (KoRV) in South Australian Koalas ().

Stephenson T, Speight N, Low W, Woolford L, Tearle R, Hemmatzadeh F Animals (Basel). 2021; 11(5).

PMID: 34065572 PMC: 8161083. DOI: 10.3390/ani11051477.

Toll-Like Receptor and Cytokine Responses to Infection with Endogenous and Exogenous Koala Retrovirus, and Vaccination as a Control Strategy.

Kayesh M, Hashem M, Tsukiyama-Kohara K Curr Issues Mol Biol. 2021; 43(1):52-64.

PMID: 33946297 PMC: 8928999. DOI: 10.3390/cimb43010005.

References

Simmons G, Young P, Hanger J, Jones K, Clarke D, McKee J . Prevalence of koala retrovirus in geographically diverse populations in Australia. Aust Vet J. 2012; 90(10):404-9. DOI: 10.1111/j.1751-0813.2012.00964.x. View

Kita Y, Hashimoto S, Nakajima T, Nakatani H, Nishimatsu S, Nishida Y . Novel therapeutic vaccines [(HSP65 + IL-12)DNA-, granulysin- and Ksp37-vaccine] against tuberculosis and synergistic effects in the combination with chemotherapy. Hum Vaccin Immunother. 2012; 9(3):526-33. PMC: 3891708. DOI: 10.4161/hv.23230. View

Ishida Y, McCallister C, Nikolaidis N, Tsangaras K, Helgen K, Greenwood A . Sequence variation of koala retrovirus transmembrane protein p15E among koalas from different geographic regions. Virology. 2014; 475:28-36. PMC: 4378583. DOI: 10.1016/j.virol.2014.10.036. View

Connolly J, Canfield P, Hemsley S, Spencer A . Lymphoid neoplasia in the koala. Aust Vet J. 1999; 76(12):819-25. DOI: 10.1111/j.1751-0813.1998.tb12337.x. View

Wong J, Bhat R, Hockman D, Logan M, Chen C, Levin A . Recombinant hepatitis C virus envelope glycoprotein vaccine elicits antibodies targeting multiple epitopes on the envelope glycoproteins associated with broad cross-neutralization. J Virol. 2014; 88(24):14278-88. PMC: 4249152. DOI: 10.1128/JVI.01911-14. View

Essex M, Sliski A, Hardy Jr W, Cotter S . Immune response to leukemia virus and tumor-associated antigens in cats. Cancer Res. 1976; 36(2 pt 2):640-5. View

Puls R, Emery S . Therapeutic vaccination against HIV: current progress and future possibilities. Clin Sci (Lond). 2005; 110(1):59-71. DOI: 10.1042/CS20050157. View

Fiebig U, Keller M, Moller A, Timms P, Denner J . Lack of antiviral antibody response in koalas infected with koala retroviruses (KoRV). Virus Res. 2015; 198:30-4. DOI: 10.1016/j.virusres.2015.01.002. View

Chappell K, Brealey J, Amarilla A, Watterson D, Hulse L, Palmieri C . Phylogenetic Diversity of Koala Retrovirus within a Wild Koala Population. J Virol. 2016; 91(3). PMC: 5244342. DOI: 10.1128/JVI.01820-16. View

10.

Waugh C, Hanger J, Loader J, King A, Hobbs M, Johnson R . Infection with koala retrovirus subgroup B (KoRV-B), but not KoRV-A, is associated with chlamydial disease in free-ranging koalas (Phascolarctos cinereus). Sci Rep. 2017; 7(1):134. PMC: 5427818. DOI: 10.1038/s41598-017-00137-4. View

11.

Brody B, Hunter E, Kluge J, Lasarow R, Gardner M, Marx P . Protection of macaques against infection with simian type D retrovirus (SRV-1) by immunization with recombinant vaccinia virus expressing the envelope glycoproteins of either SRV-1 or Mason-Pfizer monkey virus (SRV-3). J Virol. 1992; 66(6):3950-4. PMC: 241188. DOI: 10.1128/JVI.66.6.3950-3954.1992. View

12.

Diehl L, ONeil L, Hoover E . Plasma viral RNA load predicts disease progression in accelerated feline immunodeficiency virus infection. J Virol. 1996; 70(4):2503-7. PMC: 190095. DOI: 10.1128/JVI.70.4.2503-2507.1996. View

13.

Tarlinton R, Meers J, Young P . Retroviral invasion of the koala genome. Nature. 2006; 442(7098):79-81. DOI: 10.1038/nature04841. View

14.

Waugh C, Khan S, Carver S, Hanger J, Loader J, Polkinghorne A . A Prototype Recombinant-Protein Based Chlamydia pecorum Vaccine Results in Reduced Chlamydial Burden and Less Clinical Disease in Free-Ranging Koalas (Phascolarctos cinereus). PLoS One. 2016; 11(1):e0146934. PMC: 4710501. DOI: 10.1371/journal.pone.0146934. View

15.

Lombardi S, Garzelli C, Pistello M, Massi C, Matteucci D, Baldinotti F . A neutralizing antibody-inducing peptide of the V3 domain of feline immunodeficiency virus envelope glycoprotein does not induce protective immunity. J Virol. 1994; 68(12):8374-9. PMC: 237306. DOI: 10.1128/JVI.68.12.8374-8379.1994. View

16.

Blaser N, Wettstein C, Estill J, Vizcaya L, Wandeler G, Egger M . Impact of viral load and the duration of primary infection on HIV transmission: systematic review and meta-analysis. AIDS. 2014; 28(7):1021-9. PMC: 4058443. DOI: 10.1097/QAD.0000000000000135. View

17.

Groschel M, Prabowo S, Cardona P, Stanford J, van der Werf T . Therapeutic vaccines for tuberculosis--a systematic review. Vaccine. 2014; 32(26):3162-8. DOI: 10.1016/j.vaccine.2014.03.047. View

18.

Shimode S, Nakagawa S, Yoshikawa R, Shojima T, Miyazawa T . Heterogeneity of koala retrovirus isolates. FEBS Lett. 2013; 588(1):41-6. DOI: 10.1016/j.febslet.2013.10.046. View

19.

Khan M, Dhanwani R, Rao P, Parida M . Subunit vaccine formulations based on recombinant envelope proteins of Chikungunya virus elicit balanced Th1/Th2 response and virus-neutralizing antibodies in mice. Virus Res. 2012; 167(2):236-46. DOI: 10.1016/j.virusres.2012.05.004. View

20.

Hobbs M, King A, Salinas R, Chen Z, Tsangaras K, Greenwood A . Long-read genome sequence assembly provides insight into ongoing retroviral invasion of the koala germline. Sci Rep. 2017; 7(1):15838. PMC: 5696478. DOI: 10.1038/s41598-017-16171-1. View