CROSS-LINEAGE PROTECTION BETWEEN CHIKV PRIMARY INFECTION AND MAYV SECONDARY EXPOSURE IN MICE

Intro: Mayaro virus (MAYV) is a neotropical, emerging, zoonotic mosquito-borne virus that causes an acute febrile illness similar to that produced by chikungunya virus (CHIKV), a close alphavirus relative. Emergence of MAYV is sporadic and involves spillover infections, but recent outbreaks indicate that it remains a public health concern for urban emergence. With the recent arrival of both ECSA and Asian lineage CHIKV strains in the Americas, it is critical to assess their ability to cross-protect against MAYV infection. We evaluated whether CHIKV- specific immunity derived from the 3 major lineages, ECSA, IOL and Asian/American, cross-protects against MAYV infection with major genotypes L and D. Methods: We used a type I interferon-defective C57BL/6J mouse model intradermally infected with CHIKV and, 3 months later, challenged with MAYV after treatment with an anti-Ifnar1 mAb to induce a virulent phenotype. Several indexes such as weight, signs of disease and footpad swelling were monitored up to 14 days post-infection. Viremia, neutralizing antibodies, cytokine production and T cell responses were evaluated. Findings: CHIKV immunity induced by all three lineages conferred strong and broad cross-protection against MAYV infection, reducing disease severity (weight loss, footpad swelling and clinical manifestations), viremia and proinflammatory chemokine/cytokine levels. The anti-CHIKV antibodies showed the ability cross- neutralize MAYV and mice previously exposed to CHIKV developed a different profile of adaptive immune cells, showing an increase of total CD3+ and CD8+ T cells, combined with a decrease in CD4+ populations. Conclusion: Our data suggest that cross-protection observed between CHIKV and MAYV is not lineage-dependent and is mediated by both humoral and cellular responses. These data indicate that preexisting immunity produced by different CHIKV strains may reduce the impact of secondary infection by MAYV as well as the risk of human-amplified MAYV transmission, which could lead to urban emergence.