On June 2, 2016, in Recife, Brazil—the heart of the Zika outbreak—mothers ride the bus with their children, both born with microcephaly, or an abnormally small head. The birth defect is linked to the Zika virus. Image credit: Mario Tama/Getty Images

Zika virus exploded across the world earlier this year, causing a large outbreak of disease in Brazil and spreading to almost 50 countries and territories. While the typical Zika infection is mild, recent reports have strengthened the link between virus infection during pregnancy and the development of microcephaly, a rare neurological condition which leads to a small head and brain in the developing fetus. Zika also has been linked to the development of Guillan-Barre syndrome [PDF], a neurological disorder that can lead to weakness or paralysis.

New research from investigators at Harvard Medical School and collaborators at the University of Sao Paulo, Walter Reed Army Institute of Research, and Ragon Institute has suggested that we’re one step closer to a vaccine to protect vulnerable individuals against Zika virus. The researchers published their findings this week in the journal Nature.

Scientists tested two types of Zika vaccines in mice: a DNA vaccine and an inactivated, whole-virus vaccine. In DNA vaccination, the host's cell takes up the foreign DNA, and the cell then makes the proteins encoded by the DNA included in the vaccine. With an inactivated virus, the host responds directly to the injected proteins that the killed virus produced.

Lead author Dan Barouch, of Harvard Medical School's Center for Virology and Vaccine Research, explained in a press-only teleconference on July 27, “These two vaccine candidates both provided complete protection against Zika virus challenge in mice. To the best of our knowledge, this is the first report of Zika virus vaccine protection in an animal model.”

Importantly, the mice were protected against Zika after a single immunization without any need for a booster. To date, these vaccines have not been tested in pregnant mice, but Barouch notes these studies are ongoing.

The researchers caution that “care should be taken extrapolating from this mouse study to potential human efficacy.” Ben Neuman, a virologist at the University of Reading who was not involved with the study, agrees. He tells mental_floss that “while DNA vaccines work really well in mice, they tend to be a bit hit or miss in other animals, and DNA vaccines have not been particularly effective in people to this point.” No DNA vaccines are currently approved for human use in the U.S.; one is approved for horses against West Nile virus. To date, only one human DNA vaccine has been approved, for Japanese encephalitis virus in Australia.

While this study represents a step forward in the hunt for a Zika vaccine, moving a Zika vaccine from concept to clinic is a difficult prospect. While DNA vaccines may be a long shot, the prospects are also murky for other types of vaccines that have been used for humans, such as attenuated vaccines (live but weakened forms of the virus), which weren’t tested in this study. To create an inactivated vaccine for Zika, enough of the virus would need to be grown in cell cultures to be able to provide a high dose of vaccine to recipients. For a live vaccine, we would have to be careful to be sure that it wouldn’t cause any of the possible developmental or neurological effects that we see with wild-type Zika virus, including microcephaly or Guillain-Barré syndrome.

Another concern for a Zika vaccine is the potential to make other diseases, caused by related viruses, more serious. Zika is a Flavivirus and related to other viruses in this genus, including West Nile, yellow fever, Japanese encephalitis, and dengue. A second infection with dengue can actually be worse than the first, due to a phenomenon called antibody-dependent enhancement of infection. There is concern that there is potential for a Zika vaccine to induce this response.

“Antibodies are sticky molecules that float around in the blood, and many cells are covered with molecules that can catch passing antibodies," Neuman explains. "A virus like Zika may miss its chance to infect a host cell that it is poorly adapted to recognize. But if it is covered in antibodies, the virus has a better chance to infect because the antibody acts as a bridge—the cell holds onto the antibody, which sticks to the virus. This is why dengue virus is usually more severe the second or third time you catch it—the virus gets an infectious boost from antibodies left over from earlier infections. It would be wise to have a better idea of how antibodies will affect Zika virus before we start vaccinating lots of people.”

This unwelcome outcome could happen in reverse as well: The recently released dengue vaccine may make infection with Zika virus more serious, as recent laboratory models have suggested.

We’ll soon have a better idea of antibody production due to Zika vaccines in human trials. Co-author Col. Nelson Michael, of the Walter Reed Army Institute of Research, confirms to mental_floss via email that trials of the inactivated vaccine tested in this research will be moving into Phase I human trials in October—so these vaccines may soon become a reality.