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

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.

In-depth characterization of a novel live-attenuated Mayaro virus vaccine candidate using an immunocompetent mouse model of Mayaro disease

“…Meanwhile, they are considered the gold standard models to evaluate virus replication and therapeutical strategies (drugs or vaccines) due their elevated susceptibility to infection. Those data are in accordance with a previous studies by Weise et al 25 , and Webb et al 26 . The vaccine proved to be safe, inducing good immunological responses with low viral loads and no local swelling.…”

“…As for other arboviruses, such as Zika and Dengue 42,43 , resistance of adult mice to alphavirus infection is especially due to innate immune components such as type I interferons, which quickly provide an antiviral state of non-infected cells 28,29,41 . Accordingly, infection of type I interferon receptor-deficient mice (A129 −/− ) with CHIKV 29 , as well as infection of adult A129 −/− or recombination activation gene-1 deficient mice (RAG −/− ) with MAYV 26,41 provides a model that reproduces many of the clinical manifestations of human MF disease. Recently, MAYV infection of 3-4-week-old mice resulted in non-lethal models that emulated several clinical signs of MF in immunocompetent young-adult mice, such as footpad swelling, viremia and hepatic injury, although the arthritogenic effects of the virus were not investigated 26,44 .…”

“…Accordingly, infection of type I interferon receptor-deficient mice (A129 −/− ) with CHIKV 29 , as well as infection of adult A129 −/− or recombination activation gene-1 deficient mice (RAG −/− ) with MAYV 26,41 provides a model that reproduces many of the clinical manifestations of human MF disease. Recently, MAYV infection of 3-4-week-old mice resulted in non-lethal models that emulated several clinical signs of MF in immunocompetent young-adult mice, such as footpad swelling, viremia and hepatic injury, although the arthritogenic effects of the virus were not investigated 26,44 . Adding to previous studies, in the present work MAYV infection of 5-6-week-old immunocompetent BALB/c mice caused arthritis and hypernociception, major manifestations of the disease in humans.…”

“…There is no specific treatment or available vaccine to treat MAYV infection. Here, we investigated the effects of the live-attenuated MAYV/IRES vaccine 25,26 further by using the immunocompetent mouse model described above. Results showed that while mice infected with the wt MAYV strain presented elevated hypernociception from day 1 until day 21 of virus inoculation (Figs.…”

“…Here, using a wild-type (WT) strain of MAYV, we developed a model of MAYV infection in immunocompetent mice that emulates several aspects of the human disease, including arthritis and hypernociception. In parallel, we evaluated the response profile of a live-attenuated MAYV vaccine candidate (MAYV/IRES) 25,26 by conducting an in-depth characterization of clinical, virological and immunological parameters in comparison to the WT strain. Finally, we investigated the protective role of MAYV/IRES vaccination in both immunocompetent and A129 −/− (interferon type I receptor-defective) mice followed by a challenge with the virulent wt MAYV strain.…”