Study notes promising Zika antibodies; Florida suspects more local cases

Petri mouse
Petri mouse

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The search for Zika-specific antibodies that could one day be used in vaccines, tests, and possibly treatments took another step forward today, with experiments in mice that revealed some that can neutralize three different strains, along with new information on how the antibodies interact with the virus.

In other Zika developments today, the Florida Department of Health (Florida Health) reported two more suspected local Zika virus infections, pushing the number under investigation to four.

Binding behavior of Zika-specific antibodies

Researchers from Washington University School of Medicine and the National Institute of Allergy and Infectious Diseases (NIAID) reported their findings today in Cell. They said their results dovetail with a Jul 14 report in Science from another group that identified Zika-specific antibodies and the same binding site on the envelope protein on the surface of the virus

In today's report, the group infected mice with Zika, then analyzed the antibodies they produced against the virus. They identified six that recognized the E (envelope) protein of the Zika virus. Test-tube experiments showed that four of the antibodies inhibited the Asian strain, and two of those four also neutralized Zika strains from Africa and Brazil.

Using x-ray crystallography to visualize the site where the antibodies bind to the virus, the investigators learned that the two most protective antibodies bound to the same region on the E protein on the surface of the virus.

Clues could pave way for vaccines, tests, treatment

Dave Fremont, PhD, the paper's senior coauthor and professor of pathology and immunology at Washington University School of Medicine, said in a press release from the school that the findings raise the possibility of making a vaccine that could be a safer option when given to pregnant women. "We think that this piece of the viral envelope protein alone would be able to elicit a protective immune response to Zika," he said.

Vaccines made from weakened viruses are contraindicated in pregnant women, whose immune systems are suppressed. Infections from a live-virus vaccine in this group would also raise the possibility of birth defects or of miscarriage.

Looking ahead, the researchers said one of the next steps would be conducting tests on whether a vaccine based on the E protein in pregnant animals could protect developing fetuses. Also, the team wants to humanize the Zika antibodies in mice to help sort out at which stage of pregnancy they would offer the most protective effect.

Michael Diamond, MD, PhD, senior coauthor and professor of medicine at Washington University School of Medicine, said though a mouse model of Zika infection in pregnancy has been developed, the animal isn't ideal, because maternal antibodies don't cross the placenta as efficiently as they do in humans. In the statement he added that pregnancy vaccine trials would probably need to be done in non-human primates.

Another promising finding from the study was how reliably the antibodies distinguished Zika virus from closely related viruses, which the researchers said could come in handy for developing a better Zika virus test.

Diamond said current tests designed to detect the viral genome require high viral levels and can identify only those who were infected within a week of testing. Also, Zika antibodies are known to cross-react with other flaviviruses. A more targeted test, therefore, could identify the amount of Zika-specific antibodies, flagging those who were exposed months or years earlier.

Fremont said in the statement, "You really want to know not just how many people have virus in their blood right now, but also how many people have been infected over time." He added that this is especially important for pregnant women who want to know if they were infected by Zika virus earlier in their pregnancy.

Protection afforded to mice by the Zika-specific antibodies could also be useful for developing a preventive treatment in high-risk patients, though the cost might be prohibitive, especially for the duration of a pregnancy, Diamond said.

Concerning implications for subsequent dengue infections

In another set of experiments, the team found a worrisome finding: that low levels of Zika antibodies helped dengue virus—also a member of the flavirivirus family—infect cells in the lab setting. A phenomenon whereby people infected with dengue virus get sicker the second time they are infected due to low levels of leftover antibodies is called antibody-dependent enhancement (ADE). Experts have raised concerns that ADE could come into play after Zika infection or immunization with a Zika vaccine, which worsen a dengue infection that occurs afterward.

Diamond cautioned against extrapolating from cell experiments in the lab to real people. "Will Zika immunity really exacerbate dengue virus pathogenesis? All we know now is that it's possible in the laboratory."

Florida expands probe of potential local cases

In its daily Zika update, meanwhile, Florida Health said it is expanding its investigation to include the two more possible locally acquired cases, which are from Broward and Miami-Dade counties. The two locations are also the sites of the two suspected local cases reported last week.

Officials said a probe of the new cases began today with door-to-door outreach and sample collection, and they urged residents and visitors to participate in requests for urine samples needed to help gauge the number of people affected.

The pattern with the suspected local cases is consistent with that seen with past mosquito-borne illnesses, such as a 2013 dengue outbreak, Florida Health said.

Also today, officials reported 17 new travel-related cases, raising the total to 328. It noted 4 more Zika illnesses in pregnant women, lifting the state's total to 53.

See also:

Jul 27 Cell abstract

Jul 27 Washington University School of Medicine press release

Jul 27 NIAID press release

Jul 27 Cell Press news release

Jul 14 Science abstract

Jul 27 Florida Health daily Zika update

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