New Method Distinguishes Between True Infections and Cross-Reactive Antibodies in Mosquito-Borne Viruses

An international research team has developed a new antibody-based method to differentiate between genuine past infections and cross-reactive antibody responses caused by closely related mosquito-borne viruses. The method, which combines laboratory assays with mathematical modeling, was applied to over 4,000 blood samples. Researchers involved in the study state the technique is crucial for accurately mapping virus spread and improving disease control efforts.

Understanding which viruses more often cause cross-reactive antibodies is important for interpreting blood test results. – Victor Yman, Karolinska Institutet and Institut Pasteur

Research Overview and Methodology

The research was conducted by scientists from Institut Pasteur in France, Karolinska Institutet in Sweden, and other international partners. The study analyzed 4,000 blood samples collected from Peru, Senegal, French Guiana, and New Caledonia.

The core methodology involved two key components:

• Multiplex Serological Assay: Researchers measured antibodies against 28 viral proteins from nine different mosquito-borne viruses, including dengue, Zika, chikungunya, and Mayaro.
• Integrated Analysis: Laboratory test results were combined with mathematical models to identify antibody patterns indicative of a true infection. A complementary technique was used to remove cross-reactive antibodies from samples, allowing researchers to confirm whether an antibody reaction was specific to the virus being tested.

Key Findings

The application of this method yielded specific insights into antibody cross-reactivity:

• The analysis revealed that some individuals who initially appeared to have been infected with both chikungunya and Mayaro viruses had, in fact, only been infected with Mayaro. These individuals developed cross-reactive antibodies that resembled those typically induced by a chikungunya infection.
• According to the study, the chikungunya virus more frequently induces these cross-reactive antibodies than the Mayaro virus.

Victor Yman, an infectious disease physician and researcher at Karolinska Institutet and Institut Pasteur, noted that combining experimental methods with mathematical models allows for a better estimation of the extent of virus transmission in an area over time.

Context and Significance

The research is situated within the context of mosquito-borne viral diseases, which are described as a growing global public health threat. The geographical distribution of disease-spreading Aedes mosquitoes is widening as temperatures rise, increasing the risk of outbreaks in new regions, including parts of Europe.

Researchers involved in the study emphasize the practical importance of the new method. Victor Yman stated that this type of accurate mapping is crucial for preventing outbreaks and for the effective control and containment of these diseases. The study notes that more reliable methods are needed to understand how infections move through populations to prevent and quickly halt the spread of viruses.

Publication and Funding

The study, titled "Investigating antibody cross-reactivity and transmission dynamics of alphaviruses and flaviviruses using a multiplex serological assay," was published in the journal Nature Communications on April 15, 2026. The publication's DOI is 10.1038/s41467-026-71451-7.

The research was funded by the Swedish Society for Medical Research, the EU Horizon 2020 programme, the European Research Council, and several international research foundations. The researchers have reported no conflicts of interest.