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July 3, 2016: Antibodies to Dengue May Alter Course of Zika Virus Infection

Antibodies vs dengue neutralize Zika virus, but also enhance Zika infection in lab

This Zika Virus update from Emory Health Sciences.

“Scientists at Emory Vaccine Center, in collaboration with investigators from Thailand, have found that people infected with dengue virus develop antibodies that cross-react with Zika virus.

“Some of these antibodies have the potential to neutralize Zika virus — possibly providing immune protection. At the same time, in laboratory experiments, antibodies against dengue could enhance Zika virus infection of human cells.

“Zika virus is similar genetically to dengue virus and part of the same flavivirus family. They are both transmitted by Aedes mosquitos. Dengue is endemic in several countries currently experiencing Zika outbreak, leading to proposals that pre-existing dengue immunity is influencing the severity of the Zika epidemic.

“’There are really two sides of the coin here: both cross-neutralization and antibody-dependent enhancement,’ says Jens Wrammert, PhD, assistant professor of pediatrics (infectious diseases) at Emory University School of Medicine and Emory Vaccine Center. ‘We find antibody-mediated enhancement of infection with cells in the laboratory, but we have yet to clarify what effects these antibodies have on the outcome of infection in humans.’

“’Zika immune responses and disease severity may be different in dengue-endemic areas, or among dengue-experienced vs dengue-naïve groups. These factors must be taken into account when doing Zika vaccine or other clinical studies.’

There are four strains of dengue virus, and infection with one strain does not lead to long-lasting immunity against the other three. In fact, secondary infection with a different strain can increase the risk of developing a more severe illness, called dengue hemorrhagic fever.

“This is thought to happen through “antibody-dependent enhancement”: pre-existing antibodies to the first strain, unable to stop the secondary infection, instead bind to immune cells and help the new strain infect them.

“Emory scientists found that a similar phenomenon occurs with Zika. Antibodies obtained from nine dengue-infected patients at Siriraj Hospital in Bangkok — both during acute infection and after recovery — could help Zika virus (a strain isolated in 2015 from Puerto Rico) infect immune cells in cell culture.

“’It will be important to know whether anti-dengue antibodies facilitate Zika virus penetrating the placental barrier and allowing access to the developing fetus,’ says co-author Mehul Suthar, PhD, assistant professor of pediatrics (infectious disease) at Emory University School of Medicine and Emory Vaccine Center.

“All the serum samples tested were able to cross-react with Zika, both by binding and by neutralization. Nearly half the dengue-reactive monoclonal antibodies isolated bound to samples of Zika proteins. A bright spot for the future is that the team has identified potent Zika neutralizing antibodies.

“’Determining what part of the virus the various neutralizing antibodies target could help with design of vaccines or antibody-based therapies,’ Wrammert says.

Source: Science Daily

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