A pair of studies today probing the complex antibody reactions between Zika and dengue infection have both bad news and good news: that earlier dengue infection can worsen Zika infections, but a certain antibody against dengue can also neutralize Zika virus, raising the possibility of a vaccine target.
In other developments, more Zika-related birth defects were reported in the United States, along with a steep rise in the number of Puerto Ricans infected by the virus.
Drawbacks, benefits of dengue-Zika similarities
The two studies were done by the same team of researchers from Imperial College London, the Pasteur Institute, and Madihol University in Bangkok. Also, both were supported by the Wellcome Trust, the Medical Research Council, and other groups.
The team published the study on cross-reactions and enhanced Zika infection in Nature Immunology, while the report on the antibody with the potential to neutralize both viruses appeared in Nature.
The authors noted that the lab findings in the first study are in the early stages, but in a nutshell, their work suggests that previous dengue exposure enhances Zika infection. Theirs is the second study to hint that prior dengue infection might be a cofactor in Zika infection. In late April, a team from Florida Gulf Coast University found that dengue monoclonal antibodies cross-react, don't neutralize, and enhance Zika infection.
In the new study, researchers also used antibodies collected from people who had been infected with Zika virus. When the group added the antibodies to cell culture, along with Zika virus, they found that the dengue antibodies recognize and bind to Zika, but they can also worsen Zika infection through a process called antibody-dependent enhancement (ADE). Identified earlier in dengue studies, ADE is thought to trigger more serious infections following a first dengue infection.
Juthathip Mongkolsapaya, PhD, from Imperial College London, said in a press release that the next step is to investigate if ADE helps Zika virus cross the placenta. She said the team also found a group of antibodies (EDE1) that can bind to certain dengue virus sites and block Zika virus from entering immune cells.
In the second study, the researchers confirmed that EDE1 antibodies bind efficiently to Zika virus and can neutralize infection, as they do for dengue virus. Using x-ray crystallography, they determined that the binding site on the viral envelope is the same for both viruses, which they said could one day lead to a universal vaccine that protects against both of them.
In their experiments, the investigators tested two antibodies that were already known to neutralize dengue virus. One of them was even more effective at blocking Zika virus, suggesting a high level of closeness between the two viruses that surprised the team.
Jeremy Farrar, MD, PhD, director of the Wellcome Trust, said in the Imperial College press release that the viruses come from the same flavivirus family and share many genetic, transmission pattern, and immune response characteristics.
"These new studies suggest that prior infection with dengue doesn't offer any protection against Zika, and may in fact predispose people to a more severe infection," he said. "We can't say yet whether this interaction is playing a role in the current outbreak, but if confirmed it's likely to have important implications for the control and global spread of Zika, and for the development of any vaccine for the virus."
Farrar said there are still more questions than answers about Zika virus, including why explosive transmission hasn't been seen in Southeast Asia and Africa, where the virus has caused disease for several years. "This is what the international research effort needs to work out, and quickly.
US Zika birth defect totals rise
In outbreak news two more birth defects have been reported in US pregnant women infected with Zika virus, raising the total to eight as of Jun 16, the US Centers for Disease Control and Prevention (CDC) said today in a regular update. One was related to a live birth and the other in a pregnancy loss situation.
The CDC also reported the first birth outcome information in pregnant women infected with Zika virus who live in US territories. So far one pregnancy loss with birth defects had been reported as of Jun 16, which may reflect a case reported by Puerto Rico on May 13. Microcephaly was detected on ultrasound, and it wasn't clear if the woman miscarried or had an abortion.
Information on birth outcomes is from two different CDC Zika pregnancy registries: one that includes US states and the District of Columbia, and one based in Puerto Rico.
The pregnancy registries also show rising numbers of pregnant women infected with Zika virus. So far 265 have been reported from US states as of Jun 16, an increase of 31 from the previous week, and 216 have been reported in US territories, up 27 from the last report.
Puerto Rico Zika spike; more GBS, sexual transmission
The CDC also reported a steep rise in the number of Zika infections in US territories where the virus is circulating, with a steady rise in the number of US residents who have traveled to affected areas.
Zika-affected US territories reported 418 more cases since the CDC's report last week, boosting the total to 1,854, most of them in Puerto Rico. For comparison, the total rose by 135 the previous week. The CDC last week warned of a rapid Zika rise in Puerto Rico, based on what it is seeing with blood center test results. The territories also reported one more Guillain-Barre syndrome (GBS) case, putting that total at seven.
Meanwhile, the CDC reported 63 more infections in travelers as of Jun 22, increasing that total to 819. One more GBS case was received, with four now reported.
The number of sexually transmitted Zika cases stayed the same, at 11 as of Jun 22, but the Ohio Department of Health (ODH) yesterday reported its first case, involving a 61-year-old woman from Lucas County whose husband had traveled to a country with active Zika transmission. The ODH said local officials are increasing mosquito assessment and control in the areas to reduce the risk of local mosquitoes becoming infected.
Funding, outbreak spread
- Early this morning the US House of Representatives approved a $1.1 billion bill to fund the Zika virus response, but Democratic senators have threatened to sink the measure when it comes up for a Senate vote, because the bill includes $750 million in budget cuts to other health programs, USA Today reported. The vote came during an unrelated sit-in by House Democrats to protest lack of a House vote on gun control bills. The House is now adjourned until after the 4th of July holiday.
- Anguilla, a British territory in the Caribbean, is the latest location to report local Zika virus transmission, the World Health Organization (WHO) said today in its weekly situation report. It also noted that Guadeloupe has reported one more patient with a severe neurologic condition, raising its total to four. The number of countries reporting microcephaly, sexual transmission, and GBS remained the same as last week. The WHO said its risk assessment hasn't changed and that overall Zika activity isn't declining, though cases have fallen in some countries and in some parts of countries.
- The US Department of Health and Human Services (HHS) today awarded $742,000 to three health centers in American Samoa and the US Virgin Islands to help battle Zika virus. The two US territories are reporting local spread of the virus. HHS said in a statement that the money is meant to help expand preventive and primary care services, outreach, patient education, and screening. The health systems have 12 delivery sites that served nearly 26,000 patients in 2014, including 6,000 child-bearing-age women.
See also:
Jun 23 Nature Immunol abstract
Jun 23 Imperial College London press release
Jun 23 Nature abstract
Jun 23 Pasteur Institute press release
Jun 22 CDC update on birth outcomes in pregnant women infected with Zika virus
Jun 22 CDC update on Zika infections in pregnant women
Jun 22 CDC update on Zika virus in the US
Jun 22 ODH news release
