Zika-Miscarriages And Possible New Antibodies For Vaccines

Zika is now being critically associated with miscarriages after a report of a 31-year-old woman suffering from the infection in Netherlands came to light yesterday. She was 10-weeks pregnant and ostensibly contracted Zika infection during her trip to Brazil. The symptoms of infection resolved on day six after the onset. Ultrasound examination performed on day 14, showed no fetal heartbeat. Currently, there is no vaccine against Zika virus although scientists funded by Inovio Pharmaceutical Inc may be on the verge of developing a vaccine (monoclonal antibodies), as we speak.

The woman first started experiencing symptoms after returning from a trip to Suriname near the borders of northern Brazil. During her trip she did not take any precautions against Zika virus like usage of insect repellents or malaria chemoprophylaxis.

At day 21, after an amniocentesis, amniotic fluid along with fetal and placental tissue showed positive signs of Zika virus. Serum samples and urine obtained from the patient also showed presence of the virus. Serum specimen showed positive results till the 21st day and urine showed the presence of virus till the 12th day, after the onset of symptoms. Serum specimen stayed positive till the day 28.

This is not the first time that this connection has been made. Previously a MMWR report published by the Centers of Disease Control and Prevention (CDC) found that in America, of the total of the six women diagnosed with Zika infection in their first trimester, two experienced spontaneous pregnancy loss (miscarriage).

However, currently the scientist community is questioning whether Zika is the actual cause of these miscarriages or not. Because of all the pregnancies, 10-20% end up in a spontaneous miscarriage in normal circumstances.

Possible Implications Of This Association

CDC director Tom Frieden during a tele-briefing in February 2016 expressed his views on the same lines and said that the fact the virus is present in the women suffering from miscarriages does not necessarily mean that the Zika virus is actually causing them.

Most experts like Frieden are waiting on more data and research before they make a definite conclusion. This new case from Netherlands is thus an important one. Two significant observations were made by the scientists working on the 31-year-old woman who suffered the fetal loss.

First, the Zika virus could be found in the fetal tissue. This is somewhat in line with other findings made last month, which saw that the newborn and infants can have active Zika virus infection at the time of the birth.

This can potentially increase disease burden and subsequent load on the resources. Right now estimated lifetime care for a child born with Zika infected brain can cost up to $10 million, according to the White House, and the burden on the country’s financial resources could be staggering.

Secondly, the case was consistent with previous findings of Driggers and Colleagues which saw that maternal viremia was prolonged in such cases. In viremia, the virus enters the blood stream of an individual and can travel throughout the body, much like bactericemia.

In an open correspondence to the editor of the New England Journal of Medicine, Annemiek A van der Eijk (MD, PhD) from the Erasmus Medical Center, Rotterdam, the Netherlands, where the case transpired, writes, “The observation of prolonged viremia until day 21 in the patient… provides further data for consideration in the ongoing development of testing algorithms in pregnant women.”

Currently the testing procedures are based on the assumption that Zika virus viremia can only be detected for 7 days. The finding is especially important considering a prolonged Zika virus viremia could indicate possible modifications for diagnosis protocols.

Are We On Verge Of Zika Vaccines?

On the frontier of better diagnostic tests for Zika virus and infection, new antibodies were indicated by the scientists at Washington University School of Medicine in St Louis that can do the job.

The Zika virus infection spreads through Aedes Aegyptii and is usually asymptomatic (mild) in adults. Symptoms can include slight fever, headache, joint and muscle pain along with possible conjunctivitis.

Though there are rarely any deaths caused by the viral infection in adults, the infants born to mothers with Zika infection can suffer from possible neurological defects like hearing loss, feeding and visual issues, seizures and cognitive deficits like microcephaly.

The new antibody discovery could lead to not only a timely identification of cases but also to better preventive measures like vaccines and superior therapies for people with active infections.

Six different monoclonal antibodies, including 4 that were Zika virus specific (ZV48, ZV54, ZV64, and ZV67), were developed in mice. All of those were than tested and found to have a neutralizing effect to varying degrees towards Zika viral strains of different origins.

What makes this finding even more momentous is that the scientists this time pinpointed the location where antibodies interact with Zika virus, the DIII-lateral ridge. This will help the experts design a more specific and targeted vaccine in the future.

Daved Fremont, PhD, a professor of pathology and immunology and a senior researcher on the project, in a press release suggested that the possible identified site of the viral envelope protein alone (when administered) may be able to elicit a protective response of a vaccine.

Vaccines can be developed in different ways. The kind (subunit vaccines) Dr Fermont recommended is usually more secure with lesser chances of adverse events. Still the scientists suggest precautions for administrating such vaccines in pregnant women because pregnancy can suppress a woman’s immune system. Even weak vaccines can make her sick.

Michael Diamond (MD, PhD), another senior scientist, explained that to see whether such vaccines are sufficient and safe for immunizing pregnant women, other animal models would need to be explored. He suggested primates for the job rather than the mice they used in this research.

No vaccine for protection against Zika exits right now. Just last month Inovio Pharmaceutical Inc received approval from US Food and Drug Administration (FDA) to go ahead with phase 1 of their new Zika vaccine (GLS-5700) trial. This marks the first occasion where a Zika vaccine will be tested in human subjects.

The Inovio vaccine is a different kind. It uses synthetic fragments of viral DNA that are injected into the human skin. This in turn promotes T cells to generate antibodies and initiate a protective response.

Race towards a vaccine is becoming essential as the incidence of Zika virus infections in pregnant women is increasing along with new reports of microcephaly. As of yet, 12 cases of microcephaly in an infant born to pregnant infected mothers in America have been reported.

All of the cases resulted after the sexual transmission of virus from one partner who was travelling in Zika endemic areas to another. CDC also reported the first incidence of a woman transferring the Zika infection to a male partner just this month in New York.

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