In early studies on mice, a research team has found a Zika virus antibody that when given to pregnant animals protected their fetuses, and also protected adult mice from the disease, according to the Center for Infectious Disease Research and Policy.Research has found a #ZikaVirus antibody that protects pregnant animals and their fetuses Click To Tweet
The findings raise hope for a potential treatment to prevent maternal-fetal transmission of the virus to prevent microcephaly and other devastating birth defects until a vaccine is available and also may help guide vaccine development. The team, based at Washington University School of Medicine (St. Louis MO) and Vanderbilt University (Nashville TN), reported their findings last week in an early online issue of Nature.
Michael Diamond, MD, MPH, one of the study’s senior authors and professor of medicine at Washington University, said in a news release from the school that this is the first antiviral that has been shown to work in pregnancy to protect developing fetuses from Zika virus.
“This is proof of principle that Zika virus during pregnancy is treatable, and we already have a human antibody that treats it, at least in mice.” Diamond said.
In their search for an antibody candidate, the team isolated immune B cells from the blood of three infected people who had recovered, then generated 29 Zika antibodies from the cells. One of the antibodies–called ZIKV-117–neutralized all five Zika strains, including African, Asian, and American lineages.
To test the impact on active infection in adult mice, they gave infected male mice a single ZIKV-117 dose; those that got the antibody were more likely to survive, even 5 days after they were infected. The mice received a lethal dose to see how well the antibody works in the most dire conditions.
“We stacked the deck against ourselves by using a highly pathogenic strain of Zika, and even in that case, the antibody protected the mice,” Diamond said.
Next, to gauge if ZIKV-117 afforded any protection during pregnancy, researchers gave it to pregnant mice one day before or one day after they were experimentally infected with the virus. Compared with mice that didn’t get the antibody, the treatment greatly reduced virus levels in pregnant mice and their fetuses as well as in the placentas.
The team found that the placentas from the treated pregnant mice were normal and healthy, but those in untreated mice showed destruction of the placental structure, a type of damage that could impair fetal growth or cause miscarriage.
Indira Mysorekar, PhD, study coauthor and associate professor of obstetrics and gynecology at Washington University, said the group didn’t see any damage to fetal blood vessels, thinning of the placenta, or any growth restriction in the mouse fetuses.
“The anti-Zika antibodies are able to keep the fetus safe from harm by blocking the virus from crossing the placenta,” Mysorekar said.
Though work is under way on several different Zika vaccine candidates, some experts are worried about the possibility that Zika virus vaccination would worsen symptoms in those infected with the virus later, a pattern seen in dengue-infected people when the second infection involves a different strain of virus than the first. The phenomenon, called antibody-dependent enhancement (ADE) has been seen in early lab studies involving Zika virus.
To see if they could eliminate the possibility of ADE related to ZIKV-117, the authors modified the antibody so that it could not participate in the ADE process. Their experiments showed that the modified version was as effective at protecting the placenta and fetus as the unmodified type.
Part of the research team is working on developing the antibody as a possible treatment by scaling up production of ZIKV-117 and designing human studies. Another part of the group is exploring whether the antibodies could be used to clear persistent Zika infection. Both are continuing work to better define how ZIKV-117 binds to the virus and inhibits infection.
Separately, the first human trial of a the Zika vaccine candidate developed by the Walter Reed Army Institute of Research (WRAIR) (pdf) with support from the National Institutes of Health has launched, the National Institute of Allergy and Infectious Diseases announced.
The vaccine, called Zika purified inactivate virus (ZIPV), is being tested in five early-stage clinical trials, with the studies under way at the WRAIR clinical trial center in Silver Spring, MD. The vaccine is based on a system WRAIR successfully used in 2009 to develop a vaccine for Japanese encephalitis, another member of the flavivirus family.
The Biomedical Advanced Research and Development Authority (BARDA) is funding advanced development of the vaccine through a 6-year contract with Sanofi Pasteur (Paris).
Almost completely overlooked last week by the jarring presidential election results and its immediate aftermath was this incredibly positive news of discovery of an antibody that might protect a human fetus from Zika.
The treatment uses an antibody (protein) shown to be effective in preventing all known strains of the virus from replicating–in mice. This is incredibly significant as such treatment can be used to staunch the virus’s impact after someone already has been infected.
The fundamental difference between the antibody treatment and vaccine is that the latter uses bits of either live or inactivated virus or bacteria to stimulate an immune response that combats at infection by either pathogen. This is great but developing new vaccines can take decades! The antibody treatment described above, on the other hand, could be available next year.
There is currently no Zika vaccine; in the US, the FDA is trying to fight the disease using genetically modified mosquitoes.
The discovery of the ZIKV-117 antibody is a breakthrough with immense, world-wide implications. But here’s what I found interesting after reading perhaps 20 different articles about it. Vanderbilt is in the process of licensing the antibody to privately held Ridgeback Biotherapeutics, an entity about which there is almost no information whatsoever. That sentence was the full exptent of the coverage of the company. None of the new stories I read mentioned this apparent fact. Only Reuters went on to say, “Ridgeback has begun ramping up production of the antibodies in a facility designed to meet FDA manufacturing specifications.” And that was that.
Wouldn’t it be fantastic to acquire a piece of Ridgeback Biotherapeutics at this early juncture? But who or what is Ridgeback?
Incorporated in Delaware a little more than nine months ago as a Limited Liability Company, Ridgeback Biotherapeutics has an address in Miami Beach but a New York City telephone number. Its website contains exactly 4 pages, with fewer than 350 total words, combined.
The homepage says the following:
“Ridgeback Biotherapeutics is a privately held company which focuses on developing therapies and diagnostic tests for pediatric orphan and infectious diseases. We fund research and develop technologies in diseases that are typically below the radar of conventional large biotechnology and pharmaceutical companies. We focus on diseases that need champions. It is our goal and the goal of our collaborators to advance treatments and diagnostics that make a difference.”
The “Therapeutics” page says:
“We focus on pediatric orphan and infectious diseases that have limited available treatment options or none at all. Millions of people worldwide suffer every year from known and emerging infectious diseases that have few therapeutics options–primarily because these patients are in the developing world. At the other end of the spectrum, small populations of children suffer from a little known or possibly undefined disease with few stakeholders interested or capable of investment. These are the diseases that we care about. We are interested in partnering and sponsoring research with academic centers and inventors who share our same goals and values.”
The “Diagnostics” page says:
“Laboratory based diagnostic tests are a vital part of disease diagnosis. However, in most parts of the world, access is expensive or unavailable. We support research, develop and invest in technologies which bring diagnostic tools outside of the conventional lab setting.”
The “About Us” page is about one person, Ridgeback’s CEO. The text reads:
“Wendy Holman is the CEO and co-founder of Ridgeback Biotherapeutics a biotechnology company focused on pediatric and orphan infectious diseases. Prior to joining Ridgeback, Ms. Holman worked at US-based ZBI Equities, a multi-billion dollar public equity investment fund and its parent company, Ziff Brothers Investments. Between 1999 and 2014 she held various positions including healthcare sector head and director of research at ZBI Equities, and Principal at Ziff Brothers Investments. Wendy graduated from the University of Pennsylvania’s Wharton school.”
That’s it. That’s all.
As far as Ms. Holman’s personal background is concerned, life has been good to her and husband Wayne, at least from what the real estate pages of the local Miami newspapers have said about them. In the past three years, the two hedge funders have plunked down over $47 million to purchase two mansions in the swank Star Island neighborhood of Miami Beach.
So this is what I have learned so far, and it isn’t much. Not to suggest that the Holmans are hiding something, but it seems like care has been taken to divulge as little as possible in the public record and on the Internet. There’s just not enough minimal information about Ridgeback Biotherapeutics one would expect to encounter in a breaking story of such high news value.
Oh, and my email request to the company for additional information was rejected due to “invalid recipient.” Hmmm.
And there has been absolutely nothing reported in the media about what the connection is between Ms. Holman and either Washington University or Vanderbilt. That’s quite odd as Ridgeback has licensed the development rights to the ZIKV-117 antibody, a seemingly big deal because of the enormous financial opportunities of a Zika “cure.” I would love to have been a fly on the wall when Ms. Holmes, the hedge funder, was negotiating the licensing deal with two medical schools.Steve's Take: The investment opportunity on #ZikaVirus antibody seems only available to insiders Click To Tweet
In any event, if you’re not an insider, there doesn’t seem to be a way to get in on the ground floor of this investment opportunity at the moment. That, of course, could change quickly.
I promise to keep you posted.