Exposure to Chikungunya may offer partial cross-protection against Mayaro virus


A study conducted at the University of São Paulo (USP) in Brazil suggests that people previously infected with the Chikungunya virus may develop partial immunity to the Mayaro virus. The finding, presented in Journal of Virology, is based on experiments involving mice and patient blood serum. According to the authors, this type of cross-protection could be one of the reasons for the absence of a major outbreak of Mayaro fever in Brazil. The study was supported by FAPESP.

In the experiments, the mice were infected first with Chikungunya and a month later with Mayaro. The same procedure was performed in reverse order on another group of mice. The inflammatory response to the second infection was milder in both groups.

“We observed a significant reduction in secondary disease. Our analyzes have shown that cross-protection alleviates disease severity in several ways: by reducing viral load, by alleviating tissue damage, and by partially inhibiting inflammatory mediators that cause damage to cells, “said Marcílio Fumagalli, doctoral student with a FAPESP scholarship at the Virology Research Center, part of the Ribeirão Preto Faculty of Medicine (FMRP-USP). “When we tested neutralizing antibodies against one virus against another, we found a weak protective response to both.”

Although mice initially infected with Chikungunya had low levels of neutralizing antibodies in their bloodstream, these levels increased rapidly after secondary infection with Mayaro, inducing cross-protection against the latter.

The researchers analyzed the neutralization by the antibodies but also identified other factors in the immune system of the mice that could influence this cross-protection. “An infected individual is sensitized and begins to produce antibodies, as well as other defense mechanisms,” Fumagalli said. “The body develops ‘immune memory’ and can respond more quickly to reinfection.”

The levels of antibodies produced after each infection were measured. “Production of memory cells [B and T lymphocytes] takes time, but the mice infected for the first time with Chikungunya already had it, so during a secondary infection with Mayaro, the immune response was faster, including an increase in the levels of neutralizing antibodies, ”explained Fumagalli. “The immune response to pathogens is both innate [macrophages, neutrophils, natural killer cells] and adaptive [B and T lymphocytes], as well as involving soluble mediators such as antibodies and cytokines. “

In the study, we observed the important role played by antibodies, one of the factors involved in cross-protection. We also concluded that other elements need to be involved. “

Luiz Tadeu Figueiredo, Principal Investigator, Virology Research Center and Study Leader

In the analysis, the group removed B cells (which produce antibodies) from infected mice and measured the level of cross-protection. “The analysis showed that other immune response factors are involved in this cross-protection, such as lymphocyte subpopulations or innate immune response mechanisms,” Figueiredo said. “Antibodies are important, but they’re not the only ones that produce cross-protection. There’s something else we haven’t identified yet.”

The researchers also analyzed the blood serum of patients infected with Chikungunya. This experiment demonstrated that the antibodies produced in response to infection with Chikungunya also lead to cross-protection against Mayaro.

Two viruses, different antibodies

The Mayaro virus and the Chikungunya virus both belong to the Togaviridae family. The symptoms of the diseases they cause in humans are similar, but their structures are slightly different. “Each disease requires the production of different types of antibodies, although some recognize the same proteins. In other words, Mayaro and Chikungunya trigger the production of different antibodies, but some of these antibodies are effective against both diseases.” , Fumagalli said.

Chikungunya is transmitted by the bite of female mosquitoes of the species Aedes aegypti and A. albopictus. The main symptoms in most cases are high fever, headache, joint and muscle pain, nausea, fatigue, and rash. Joint pain can remain sharp for several years.

Mayaro is transmitted by a sylvan vector, the mosquito Hemagogus spp. The main symptoms are the sudden onset of fever, rash, dizziness, chills, headache and muscle pain. Severe cases also involve joint pain, which may or may not be accompanied by edema. No vaccine exists for either disease.

Cross protection is unusual but not unknown to immunologists. The case of dengue, for example, which is a flavivirus, is more complex. “First of all, there are four serotypes of the same species. The immune response to each is different. Antibodies to one can protect against another, but some antibodies can make the disease worse,” Figueiredo said.

Urban adaptation

Confirmation of cross-protection between Mayaro and Chikungunya also explains why the old disease does not circulate widely in Brazilian cities despite the appearance of outbreaks in recent years and warnings issued by health authorities. “The discovery raises the hypothesis that cross-immunity may be an evolutionary barrier against the adaptation of the Mayaro virus to the urban environment,” Figueiredo said. “Both pathogens are endemic to Brazil but only Chikungunya has adapted enough to circulate in cities. Mayaro is predominantly sylvan.”

Fumagalli pointed out that factors other than cross-protection can block transmission of Mayaro. “To infect humans, the virus would have to adapt efficiently in order to be transmitted to urban mosquitoes, but in fact it is mainly transmitted between monkeys and other wild mosquitoes,” he said.

Another key factor in the differences between the two diseases is viremia. Mayaro produces a low viral load in humans for a short time after infection, which further reduces the susceptibility of urban mosquitoes. “In other animals, like monkeys, the viral load is significantly higher, which may also explain this evolutionary barrier that prevents Mayaro from circulating in urban environments,” Fumagalli said. “Our study suggests that prior immunity may be an obstacle to the circulation of Mayaro in humans, since subjects infected with Chikungunya are partially protected, which could help control further outbreaks.”


São Paulo Research Foundation (FAPESP)

Journal reference:

Fumagalli, MJ, et al. (2021) Exposure to Chikungunya virus partially protects against Mayaro virus infection in mice. Journal of Virology. doi.org/10.1128/JVI.01122-21.

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