Research group develops new methodology to diagnose Zika

An antibody that bonds specifically to Zika virus has been identified. Research findings were presented at the São Paulo School of Advanced Science in Arbovirology.

By Karina Toledo, in São José do Rio Preto  |  Agência FAPESP – Researchers at the University of São Paulo’s Medical School (FM-USP) in Brazil and Miami University in the United States have identified an antibody in patients’ blood that binds very specifically to Zika virus, enabling researchers to develop a test for the serological diagnosis of Zika virus infections.

The results of trials to validate the new methodology will be published soon in PLOS Neglected Tropical Diseases. Preliminary findings were presented by Esper Kallás, a professor at FM-USP, during the São Paulo School of Advanced Science in Arbovirology. Supported by FAPESP, the event was held in early June in São José do Rio Preto, São Paulo State.

“The antibodies usually found in Zika patients cross-react with dengue virus. The serological tests available to date may therefore be unable to identify patients who have really been infected by Zika in the past,” Kallás told Agência FAPESP.

The strategy used by the group at FM-USP and collaborators was to analyze blood from patients with a confirmed diagnosis of Zika infection in search of blood cells called plasmablasts, using molecular tests capable of detecting infection only during the acute phase, shortly after viral RNA circulates in the organism.

“We sequenced each of these blood cells to identify the immunoglobulin molecules they produced,” Kallás said. “One of the antibodies we found, and which we called P1F12, binds only to Zika virus and doesn’t cross-react with dengue virus.”

If the serological test does prove capable of identifying people previously infected by Zika virus, it would have several applications. For example, it would be useful to help assess the risk faced by pregnant women who need to travel to an area in which the disease is prevalent. “If they know for sure they’ve had Zika in the past, they can travel with some peace of mind. Otherwise they should take more precautions,” Kallás said.

It could also be used by public health authorities to estimate the percentage of people in a given population who have never been infected and thus are susceptible to the virus, helping to prevent fresh outbreaks and to organize healthcare services. 

The methodology could contribute to future research geared towards the development and validation of vaccines against dengue and against Zika. “For this kind of research, it’s important to know whether participants have had either disease or both, as this can influence the result,” Kallás said. “A serological test that distinguishes between the two would help save a lot of resources.”

According to Kallás, the antibody P1F12 was not found to be highly effective in neutralizing Zika virus, but his presentation mentioned ongoing studies by other groups to identify antibodies that can be used to treat and prevent the disease. 

“It would be interesting, for example, for a pregnant woman who discovers the virus early in the pregnancy,” he said. “Administering neutralizing antibodies could prevent the transmission of Zika virus to the baby.”

Challenges for the Zika research network

On the first day of the São Paulo School of Advanced Science in Arbovirology, Paolo Zanotto, a professor at the University of São Paulo’s Biomedical Science Institute (ICB-USP), said that one of the main challenges for Zika-related research was the development of a really effective serological test.

Zanotto coordinates the Zika Virus Research Network in São Paulo (Rede Zika), supported by FAPESP. “When the network began, four priorities had been set internationally: diagnosis, vaccines, understanding the relationship between Zika and microcephaly, and organizing cohorts of infected pregnant women for long-term monitoring of the effects on their babies,” he said.

“We’ve already shown that the virus can cause congenital alterations in animals. The same models have been used to establish proof-of-concept for promising candidate vaccines. We’ve shown that these potential vaccines immunize rodents and monkeys, and we have evidence that they can work in humans. Also, patient cohorts have been established in São José do Rio Preto, Ribeirão Preto, Campinas, Jundiaí, and several other places in Brazil. The priority on which more still needs to be done is serological diagnosis.”

The studies performed so far have shown that microcephaly is not the only manifestation of congenital infection by Zika.

“There’s a gradient of manifestations ranging from severe anencephaly to minor alterations that are almost imperceptible, and cognitive alterations may occur without morphological abnormalities,” Zanotto said. “A complete description of the disease will be possible only when we’ve followed these cohorts long enough for all manifestations to have appeared in sufficient quantities to give us a statistical basis.”

Internationalization

Organized by researchers at the São José do Rio Preto Medical School (FAMERP) in São Paulo State, Brazil, and University of Texas Medical Branch in the United States, the São Paulo School of Advanced Science in Arbovirology was attended by some of the world’s leading researchers in arbovirology.

Approximately 100 graduate students and postdoctoral researchers from Brazil and abroad were selected to take part in the event, which consisted of practical activities and fieldwork, as well as presentations.

During the opening session, FAPESP CEO Carlos Américo Pacheco highlighted the importance that his organization places on funding this type of initiative.

“Over the past decade, we have sought a more international approach with the aim of improving the quality of the research done in São Paulo,” he said. “We have invited people from abroad to spend some time in Brazil and sent students overseas. This is strategic. And with the same goal in mind, we have funded several São Paulo Schools of Advanced Science in recent years.”

According to Walter Colli, a member of FAPESP’s Life Sciences Adjunct Panel, this was the 50th São Paulo School of Advanced Science. “These Schools are opportunities to bring researchers together to exchange ideas and train,” he said. “They’re one of the best ideas we’ve ever had.”