Taking steps toward making a Zika virus vaccine

Part 2

The history of the Zika virus goes back to 1947, when British scientists cultured it from a sick rhesus monkey that had been deliberately exposed to mosquitoes in the Zika forest of Uganda. The virus spread eastward to Asia and recently to islands in the Pacific — Yap in Micronesia, the French territory of New Caldonia and other islands — before arriving in northwestern Brazil, where its association with human microcephaly was established.  

Zika virus has eight or nine genes, while humans have 20,000 or so. We know a lot about Zika genes, and what they do, because Zika is a flavivirus (flavus means yellow in Latin). It has at least 70 known relatives, some of which, like yellow fever, West Nile, and the dengue fever viruses, are well-studied. These viruses have similar genes and there are effective vaccines for many of them. Does this give us hope to find a clear path to a Zika vaccine?

Many researchers are trying. In the Aug. 25 issue of Nature (a British journal read by most scientists), an article by Dan Barouch and multiple colleagues, “Vaccine protection against Zika virus from Brazil,” reported on an experiment where one gene of Zika virus DNA was inserted into a circle of DNA called a plasmid. The gene in question, the env gene, provides the instructions to make an envelope protein that sticks out of the membrane coat of the virus. 

The idea was to inject the plasmid DNA into the muscle cells of mice, and have the muscle cells make the Zika envelope protein, inducing an immune response and protecting the host.

Experience with other so-called DNA vaccines suggests that the protein made by the injected DNA should provoke the mouse’s immune system. This it did — in dramatic fashion — and the mice produced anti-Zika antibodies. So far so good, but do these antibodies protect the mice? 

Yes, actually. Mice making no Zika components were injected with Zika virus and they got sick, produced millions of viruses per milliliter of blood, but did not die. The mice with the antibodies injected with Zika, however, were totally immune; the virus never had a chance. 

These researchers (there are 26 authors from five institutions) did more. They showed that purified, killed Zika virus injected into mice also provided protection. This is a standard way of making a vaccine. Finally, a purified antibody transferred from vaccinated into unvaccinated mice protected them from Zika virus infection, by so-called passive immunity. 

I also found an impressive paper by a group from Washington University in St. Louis, published in the journal Cell in August. They have made and studied monoclonal antibodies that neutralize the Zika virus and could be used to provide passive immunity. Monoclonal antibodies can be produced in large amounts, so this is hopeful as well, as they could be used to prevent infection in pregnant women.

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Mice, of course, are not humans and results from mice do not always hold in people. Lab mice are essentially identical twins; humans are infinitely diverse. So, are human trials starting? One has begun, and it uses the same or similar plasmid as the mouse experiments. You can look it up: go to www.ClinicalTrials.gov and search for Zika and vaccine.  (All clinical trials have to be registered.) 

In order to take part in this clinical trial, you would have to go to Emory University in Atlanta, the University of Maryland in Baltimore or the National Institutes of Health in Bethesda and be ready to make 18 follow-up visits, so I suspect these medical centers will provide most of the volunteers. 

Zika virus causes mild disease if you are not pregnant, so the Institutional Review Boards at these places have probably approved trials that inject humans with Zika virus, assuming informed consent by the volunteers. If this were Ebola, this approach would and could not happen.

Vaccines and clinical trials cost money, as do mosquito abatement programs, but a $1.1 billion funding bill is stalled in the U.S. Congress right now. The Senate passed it, but the House version took money away from Ebola research, Planned Parenthood and Obamacare implementation. Senate Democrats refused to go along, calling it extortion. 

There the matter stands, as it failed another vote since Congress has returned. Dr. Anthony Fauci at the National Institute of Arthritis and Infectious Diseases has shifted money from Ebola vaccines to Zika, but Ebola will be back.  

Director Tom Frieden at the Centers for Disease Control is also doing what he and his scientists and physicians can, but if Aedes aegypti spreads north next spring, or the virus shifts to the cold-resistant Aedes albopictus, the infections could shift north and will be a potential disaster for many families, as it is now for families in Puerto Rico, other islands in the Caribbean and South America.

Richard Kessin is professor emeritus of pathology and cell biology at Columbia University Medical Center. He lives in Norfolk and can be reached at rhk2@columbia.edu. See Donald G. McNeil Jr.’s book, “Zika: The Emerging Epidemic,” for a history of the virus and its effects.