Vaccines, Vol. 8, Pages 209: Arthritogenic Alphavirus Vaccines: Serogrouping Versus Cross-Protection in Mouse Models

Vaccines, Vol. 8, Pages 209: Arthritogenic Alphavirus Vaccines: Serogrouping Versus Cross-Protection in Mouse Models:

Vaccines, Vol. 8, Pages 209: Arthritogenic Alphavirus Vaccines: Serogrouping Versus Cross-Protection in Mouse Models

Vaccines doi: 10.3390/vaccines8020209

Authors:
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


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.