Arthritogenic Alphavirus Vaccines: Serogrouping Versus Cross-Protection in Mouse Models
Wilson Nguyen,
Eri Nakayama,
Kexin Yan,
Bing Tang,
Thuy T. Le,
Liang Liu,
Tamara H. Cooper,
John D. Hayball,
Helen M. Faddy,
David Warrilow,
Richard J. N. Allcock,
Jody Hobson-Peters,
Roy A. Hall,
Daniel J. Rawle,
Viviana P. Lutzky,
Paul Young,
Nidia M. Oliveira,
Gunter Hartel,
Paul M. Howley,
Natalie A. Prow,
Andreas Suhrbier
Affiliations
Wilson Nguyen
Inflammation Biology Group, QIMR Berghofer Medical Research Institute, Brisbane 4029, Australia
Eri Nakayama
Inflammation Biology Group, QIMR Berghofer Medical Research Institute, Brisbane 4029, Australia
Kexin Yan
Inflammation Biology Group, QIMR Berghofer Medical Research Institute, Brisbane 4029, Australia
Bing Tang
Inflammation Biology Group, QIMR Berghofer Medical Research Institute, Brisbane 4029, Australia
Thuy T. Le
Inflammation Biology Group, QIMR Berghofer Medical Research Institute, Brisbane 4029, Australia
Liang Liu
Experimental Therapeutics Laboratory, School of Pharmacy & Medical Sciences, University of South Australia Cancer Research Institute, SA 5000, Australia
Tamara H. Cooper
Experimental Therapeutics Laboratory, School of Pharmacy & Medical Sciences, University of South Australia Cancer Research Institute, SA 5000, Australia
John D. Hayball
Experimental Therapeutics Laboratory, School of Pharmacy & Medical Sciences, University of South Australia Cancer Research Institute, SA 5000, Australia
Helen M. Faddy
Research and Development Laboratory, Australian Red Cross Lifeblood, Kelvin Grove, Qld 4059, Australia
David Warrilow
Public Health Virology Laboratory, Queensland Health Forensic and Scientific Services, PO Box 594, Archerfield, Qld 4108, Australia
Richard J. N. Allcock
School of Biomedical Sciences, University of Western Australia, Crawley 6009, Australia
Jody Hobson-Peters
School of Chemistry and Molecular Biosciences, University of Queensland, St Lucia, Qld 4072, Australia
Roy A. Hall
School of Chemistry and Molecular Biosciences, University of Queensland, St Lucia, Qld 4072, Australia
Daniel J. Rawle
Inflammation Biology Group, QIMR Berghofer Medical Research Institute, Brisbane 4029, Australia
Viviana P. Lutzky
Inflammation Biology Group, QIMR Berghofer Medical Research Institute, Brisbane 4029, Australia
Paul Young
School of Chemistry and Molecular Biosciences, University of Queensland, St Lucia, Qld 4072, Australia
Nidia M. Oliveira
Deptartment of Microbiology, University of Western Australia, Perth, WA 6009, Australia
Gunter Hartel
Statistics Unit, QIMR Berghofer Medical Research Institute, Brisbane, Qld 4029, Australia
Paul M. Howley
Sementis Ltd., Berwick, VIC 3806, Australia
Natalie A. Prow
Inflammation Biology Group, QIMR Berghofer Medical Research Institute, Brisbane 4029, Australia
Andreas Suhrbier
Inflammation Biology Group, QIMR Berghofer Medical Research Institute, Brisbane 4029, Australia
Chikungunya virus (CHIKV), Ross River virus (RRV), o’nyong nyong virus (ONNV), Mayaro virus (MAYV) and Getah virus (GETV) represent arthritogenic alphaviruses belonging to the Semliki Forest virus antigenic complex. Antibodies raised against one of these viruses can cross-react with other serogroup members, suggesting that, for instance, a CHIKV vaccine (deemed commercially viable) might provide cross-protection against antigenically related alphaviruses. Herein we use human alphavirus isolates (including a new human RRV isolate) and wild-type mice to explore whether infection with one virus leads to cross-protection against viremia after challenge with other members of the antigenic complex. Persistently infected Rag1-/- mice were also used to assess the cross-protective capacity of convalescent CHIKV serum. We also assessed the ability of a recombinant poxvirus-based CHIKV vaccine and a commercially available formalin-fixed, whole-virus GETV vaccine to induce cross-protective responses. Although cross-protection and/or cross-reactivity were clearly evident, they were not universal and were often suboptimal. Even for the more closely related viruses (e.g., CHIKV and ONNV, or RRV and GETV), vaccine-mediated neutralization and/or protection against the intended homologous target was significantly more effective than cross-neutralization and/or cross-protection against the heterologous virus. Effective vaccine-mediated cross-protection would thus likely require a higher dose and/or more vaccinations, which is likely to be unattractive to regulators and vaccine manufacturers.
