Effects of Chikungunya virus immunity on Mayaro virus disease and epidemic potential

Emily M Webb,Scott C Weaver,Sherry L Haller,Christine V F Carrington,Huanle Luo,Sasha R Azar,Rose M Langsjoen,Shannan L Rossi,Kenneth Plante,Tian Wang,Anushka T Ramjag,Candace E Cuthbert,Albert J Auguste,Graham Simmons

doi:10.1038/s41598-019-56551-3

Abstract

Mayaro virus (MAYV) causes an acute febrile illness similar to that produced by chikungunya virus (CHIKV), an evolutionary relative in the Semliki Forest virus complex of alphaviruses. MAYV emergence is typically sporadic, but recent isolations and outbreaks indicate that the virus remains a public health concern. Given the close phylogenetic and antigenic relationship between CHIKV and MAYV, and widespread distribution of CHIKV, we hypothesized that prior CHIKV immunity may affect MAYV pathogenesis and/or influence its emergence potential. We pre-exposed immunocompetent C57BL/6 and immunocompromised A129 or IFNAR mice to wild-type CHIKV, two CHIKV vaccines, or a live-attenuated MAYV vaccine, and challenged with MAYV. We observed strong cross-protection against MAYV for mice pre-exposed to wild-type CHIKV, and moderately but significantly reduced cross-protection from CHIKV-vaccinated animals. Immunity to other alphavirus or flavivirus controls provided no protection against MAYV disease or viremia. Mechanistic studies suggested that neutralizing antibodies alone can mediate this protection, with T-cells having no significant effect on diminishing disease. Finally, human sera obtained from naturally acquired CHIKV infection cross-neutralized MAYV at high titers in vitro. Altogether, our data suggest that CHIKV infection can confer cross-protective effects against MAYV, and the resultant reduction in viremia may limit the emergence potential of MAYV.

Highlights

Chikungunya virus (CHIKV) is a close alphavirus relative of Mayaro virus (MAYV) and a fellow member of the Semliki Forest complex
Mice vaccinated with MAYV/IRES developed high (>640) MAYV-neutralizing antibody titers and mice vaccinated with TC-83 presented with typical Venezuelan equine encephalitis virus (VEEV)-neutralizing antibody titers (≤320)
Our studies in immunocompetent C57/B6J mice show that immunity derived from wild-type CHIKV (CHIKV-99659) infection diminished MAYV disease and completely prevented MAYV viremia

Summary

Introduction

Chikungunya virus (CHIKV) is a close alphavirus relative of MAYV and a fellow member of the Semliki Forest complex. CHIKV infection results in a similar disease presentation, characterized by persistent, debilitating arthralgia, and has a comparable sylvatic transmission cycle to that of MAYV, but in sub-Saharan Africa It has a long history of emergence into a peridomestic, human-amplified cycle and of invading Asia, the Indian Ocean Basin[31], and recently the Americas in 201332. A live-attenuated CHIKV vaccine candidate (e.g. CHIKV/ IRES) elicits a strong cross-neutralizing antibody response to o’nyong-nyong virus (ONNV), a close relative of CHIKV, and provides complete protection from ONNV but not Ross river virus disease in mouse models[34]. Fox et al screened a panel of anti-CHIKV mouse monoclonal antibodies (mAbs) for cross-neutralizing potential against other alphaviruses (i.e. ONNV, MAYV, Semliki Forest virus, and Ross River virus), and demonstrated that a single anti-CHIKV mouse mAb completely protects mice from MAYV disease and mortality[36]. These data suggest a certain threshold of CHIKV immunity is needed to protect against MAYV disease, such that the chimeric or live-attenuated CHIKV vaccines are unlikely to control a MAYV outbreak, while naturally acquired CHIKV immunity (wild-type CHIKV infection) may be adequate to provide protection and reduce viremias sufficiently to impede outbreaks

Methods

Results

Conclusion