An international team of researchers has developed an innovative strategy for producing new vaccines. They created a genetically modified version of the Chikungunya virus that replicates only once, yet still trains the immune system to defend itself without causing disease. In tests conducted on mice, a single dose of the formulation containing the modified immature virus was sufficient to generate antibodies and protect the rodents against lethal infection.
The study was published in May in the journal NPJ Vaccines and was conducted by scientists from the University of São Paulo (USP) in Brazil and the University of Bonn in Germany. It paves the way for a new vaccine platform. In addition to protecting against chikungunya, the technology developed by the researchers can be adapted to combat other diseases.
"The idea was to create a virus that enters the cell and activates the immune system but is physically incapable of becoming infectious. Thus, the vaccinated individual doesn't experience symptoms nor are they at risk of developing the disease. That's important because it allows for robust protection without the risk of side effects, expanding its use to include immunocompromised individuals and older adults," explains Danillo Lucas Alves Esposito , a researcher at the Ribeirão Preto School of Pharmaceutical Sciences at the University of São Paulo (FCFRP-USP) and author of the study. Esposito is supported by FAPESP through a Young Investigator Grant .
Traditionally, vaccines are produced to train the immune system using attenuated viruses, which are weakened through genetic mutations, or inactivated viruses, which are unable to replicate. "In this study, we sought to combine the efficacy of attenuated-virus vaccines with the safety of inactivated vaccines," Esposito says.
In addition to attenuated and inactivated virus vaccines, more recent platforms include protein subunit, recombinant, conjugate, viral vector, DNA, and RNA vaccines. Rather than using the entire virus, these vaccines use fragments, proteins, or genetic instructions to induce an immune response.
The new platform proposed by the international team uses a unique strategy involving the inoculation of viruses that cannot mature within the host cell. As a result, the viruses do not become infectious but still provide protection against future infections.
"That's important because we currently have an attenuated virus vaccine against chikungunya that was reapproved by the FDA [the U.S. agency that regulates drugs] in 2025, albeit with restrictions, after a period of suspension. It isn't recommended for very young children, older adults, immunocompromised individuals, or those with certain comorbidities because it may cause adverse effects," he says.
Non-virulent, but with an immune response
The researcher explains that almost all viruses undergo a maturation process that is essential for them to become infectious. In the case of arboviruses, such as Chikungunya, Zika, dengue, and yellow fever, this maturation occurs at the end of the replication cycle within the host cell.
"Specifically, in the case of Chikungunya, maturation depends on the removal of a surface protein [E3], which covers the protein [E2] responsible for allowing the virus to enter the cell. When E3 isn't removed, E2 remains hidden, and the virus can't infect the cell," the researcher explains to Agência FAPESP.
In the natural life cycle of the Chikungunya virus, furin, a host enzyme, plays the role of removing the E3 protein and allowing E2 to act as the key to invading the next cell. To develop the vaccine using immature viruses, therefore, the scientists used human cells derived from colon cancer tissue (LoVo), which lack the furin enzyme.
Tips for editing the genome
Esposito explains that the virus must replicate at least once inside the cell to generate an immune response. For this reason, the researchers modified the viral genome by replacing the region recognized by furin with a sequence identified by an enzyme from a plant-infecting virus, the tobacco mosaic virus, which does not affect humans or mosquitoes.
"Thus, the virus is artificially 'activated' before vaccination. However, since this enzyme isn't present in the human body, the virus can't cause new infections," says Esposito.
After this initial, controlled replication, all the resulting viruses are immature and incapable of infecting other cells. "They function solely as antigens, serving as a model for the immune system," Esposito adds.
Another interesting finding from the study was that the immunized animals demonstrated the ability to neutralize the Mayaro virus in addition to being protected against Chikungunya, suggesting broader protective potential. "Since several arboviruses rely on furin to become infectious, the platform can be adapted for Zika, yellow fever, and even variants of SARS-CoV-2, for example" he says.
"It's an interesting platform. Now, in addition to moving forward with clinical trials, we're interested in using this vaccine platform for other arboviruses," he states.
About São Paulo Research Foundation (FAPESP)
The São Paulo Research Foundation (FAPESP) is a public institution with the mission of supporting scientific research in all fields of knowledge by awarding scholarships, fellowships and grants to investigators linked with higher education and research institutions in the State of São Paulo, Brazil. FAPESP is aware that the very best research can only be done by working with the best researchers internationally. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research organizations in other countries known for the quality of their research and has been encouraging scientists funded by its grants to further develop their international collaboration. You can learn more about FAPESP at www.fapesp.br/en and visit FAPESP news agency at www.agencia.fapesp.br/en to keep updated with the latest scientific breakthroughs FAPESP helps achieve through its many programs, awards and research centers. You may also subscribe to FAPESP news agency at http://agencia.fapesp.br/subscribe
