An experimental Zika vaccine lowered levels of virus in pregnant monkeys and improved fetal outcomes in a rhesus macaque model of congenital Zika virus infection, according to a new study in Science Translational Medicine.
The research was conducted by scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and their collaborators from the University of California, Davis; Duke University, Durham, North Carolina; and the University of California, Los Angeles. NIAID scientists developed the experimental vaccine and currently are evaluating it in a Phase 2 human clinical trial. The vaccine uses a small circular piece of DNA, or plasmid, containing genes that encode Zika virus surface proteins to induce an immune response.
Zika virus is primarily transmitted to humans by Aedes mosquitoes; it also can be transmitted through sex. The virus can cause serious birth defects in babies born to mothers who become infected during pregnancy. Ideally, the authors note, a Zika vaccine would be given to adolescents and adults of childbearing age before pregnancy to prevent congenital Zika syndrome.
Large outbreaks of Zika virus in the Americas in 2015 and 2016 led to thousands of cases of congenital Zika syndrome, prompting NIAID scientists to quickly develop and begin clinical trials of the NIAID DNA Zika vaccine. While clinical trials can yield data on safety and how the vaccine performs in recipients, due to the diminished incidence of Zika, conducting a clinical trial that would determine the vaccine’s ability to prevent adverse fetal outcomes has been logistically difficult. Therefore, researchers developed a macaque model of congenital Zika syndrome to provide another way to evaluate the experimental vaccine.
Their study compared outcomes in 12 unvaccinated pregnant macaques and 13 macaques vaccinated before pregnancy. All macaques were exposed to Zika virus a total of three times during the first and second trimesters. Vaccinated animals had a significant reduction in the amount of Zika virus in the blood and in the length of time virus was detectable compared to unvaccinated animals. The vaccinated group was significantly less likely to transmit Zika virus to the fetus, whereas persistent Zika virus infection in unvaccinated macaques was associated with fetal infection. No cases of early fetal loss occurred in the vaccinated group, which also had no evidence of damage to either the placenta or the fetal brain.
The study suggests that sterilizing immunity — an immune response that prevents infection entirely, with no detectable virus — may not be required for significant protection against congenital Zika syndrome, according to the authors. They note that the ability of a vaccine to prevent persistent Zika virus infection may be an important consideration for future clinical research. Meanwhile, the animal model can be used to learn more about Zika virus transmission from mother to fetus and possible intervention strategies.
For many of us, pesky mosquitoes are part of life outdoors during the summer months. While some people consistently find themselves covered in bites after an evening outside, others may rarely get bitten. This puzzling phenomenon—why mosquitoes choose to bite some people over others—is actually an important area of research for infectious disease experts.
Mosquito bites can be more than just an itchy nuisance in certain parts of the world. Mosquitoes can carry parasites, viruses, and worms, and spread deadly infections. In select parts of the United States, mosquitoes have transmitted viruses such as chikungunya, dengue, West Nile, and Zika. Mosquitoes found in other parts of the world can spread filariasis and malaria—a disease that caused 435,000 deaths worldwide in 2017.
One element all mosquitoes have in common is their complex sense of smell. Mosquitoes must seek out blood meals (a mosquito “bite” to humans) to reproduce and water sources to lay eggs; however, they have poor vision and instead use scent to find their next meal.
Mosquitoes have exquisitely sensitive small hairs (known as sensillae) on their antennae and mouth parts. These hairs have scent receptors that help the mosquitoes distinguish among and select hosts. However, the scents that attract mosquitoes, and why they choose to bite some people over others, is still not well understood. Various NIAID-supported scientists hope to learn more through basic and translational research projects on mosquito olfaction (the sense of smell), host-seeking behavior, and host identification.
Researchers have long known that mosquitoes are attracted to the human scent of sweat, which includes the odor of lactic acid. The mechanisms behind this attraction remained a mystery, until recently. A NIAID-funded team of investigators have identified a unique odor receptor, known as Ionotropic Receptor 8a (IR8a), that is used by the Aedes aegypti mosquito to detect lactic acid. Led by Dr. Matthew DeGennaro of Florida International University, the research team mutated various receptors of Aedes aegypti, a mosquito that transmits diseases such as dengue and Zika, to study the effects on olfaction. When they mutated IR8a, which is located on the antennae, researchers discovered that the mosquitoes were incapable of sensing lactic acid and other acidic smells in human odor. The findings, published in Current Biology,(link is external) could lead to the development of new and improved mosquito attractants and repellents. If researchers know how mosquitoes find people, they can develop novel ways to target those mechanisms.
NIAID also is applying concepts from basic research on mosquito olfaction to support the development and testing of novel tools for mosquito control. These include traps that use attractants to lure mosquitoes searching for a meal or a site to lay eggs. Scientists also are working to develop repellents, including improved, environmentally friendly products for personal and spatial protection. Investigators hope that mosquito olfaction research will lead to new ways to prevent mosquitoes from finding and biting people, and, ultimately, reduce the transmission of mosquito-borne diseases.
Reference: JI Raji et al.Aedes aegypti mosquitoes detect acidic volatiles found in human odor using the IR8a pathway. Current Biology DOI: 10.1016/j.cub.2019.02.045 (2019)
Infections that can affect the health of the pregnant woman, the pregnancy, and the baby after delivery include (but are not limited to):
Bacterial vaginosis (pronounced vaj-in-NOH-sis) is the most common vaginal infection in women of reproductive age. It increases the risk of contracting sexually transmitted infections (STIs) and may play a role in preterm labor. The condition results from a change in the balance of bacteria that normally live in the vagina. Having unprotected sex and douching can increase the risk of bacterial vaginosis. The Centers for Disease Control and Prevention (CDC) recommends that pregnant women get tested for bacterial vaginosis if they have symptoms and get treated if necessary.
Chlamydia infection during pregnancy is associated with an increased risk of preterm birth and its complications. If the infection is present and untreated at the time of delivery, it can lead to eye infections or pneumonia in the infant. In most hospitals, infants’ eyes are routinely treated with an antibiotic ointment shortly after birth. The ointment can prevent blindness from exposure to chlamydia bacteria during delivery in case the pregnant woman had an undetected infection.
Cytomegalovirus (CMV) (pronounced sahy-toh-meg-uh-loh-VAHY-ruhs) is a common virus present in many body fluids that can be spread through close personal contact, such as kissing or sharing eating utensils, as well as sexual contact. The virus usually does not cause health problems, but once it is in a person’s body, it stays there for life and can reactivate at different times. A pregnant woman may not even know she has the infection, and she may pass the virus on to her fetus, causing congenital CMV infection. Most infants with congenital CMV infection never show signs or have health problems. However, some infants have health problems such as hearing or vision loss, seizures, or intellectual disabilities that are apparent at birth or that develop later during infancy or childhood. Currently, routine screening for CMV during pregnancy is not recommended. Researchers are working on treatments for CMV and vaccines to try to prevent new infections during pregnancy and to reduce the risk of transmission to the infant. Congenital CMV infection can be diagnosed by testing a newborn baby’s saliva, urine, or blood. Treatment with antiviral drugs may decrease the risk of health problems and hearing loss in some infected infants.
Fifth disease is caused by human parvovirus (pronounced PAHR-voh-vahy-ruhs) type B19. The virus causes a common childhood disease that spreads easily from person to person. Children who get it usually have a fever and a red rash on their cheeks. Parvovirus B19 usually does not cause problems for pregnant women or the fetus, but in rare cases, the woman might have a miscarriage or the fetus could develop anemia. There is no vaccine or treatment for fifth disease. You can reduce your chance of being infected with parvovirus B19 or infecting others by avoiding contact with people who have parvovirus B19 and by thoroughly and regularly washing your hands. Sometimes health care providers recommend testing pregnant women to see if they are immune to the virus already.
Untreated gonorrhea infection in pregnancy has been linked to miscarriage, preterm birth and low birth weight, premature rupture of the membranes surrounding the fetus in the uterus, and infection of the fluid that surrounds the fetus during pregnancy. Gonorrhea can also infect an infant during delivery as it passes through the birth canal. If untreated, infants can develop eye infections and blindness. In most hospitals, infants’ eyes are routinely treated with an antibiotic ointment shortly after birth to prevent eye problems from exposure to gonorrhea during delivery, in case the pregnant woman had an undetected infection. Treating gonorrhea as soon as it is detected in pregnant women reduces the risk of transmission.
Group B streptococcus (GBS) can cause serious health problems in infants. But giving antibiotics during labor can prevent the spread of GBS, so it’s important to get tested for the infection during pregnancy. Learn more about GBS and pregnancy.
Pregnant women who get infected with genital herpes late in pregnancy have a high risk of infecting their fetus. The risk of infection is particularly high during delivery. Herpes infections in newborns are serious and potentially life-threatening. Infection with the herpes virus during pregnancy or at the time of delivery can lead to brain damage, blindness, and damage to other organs. Rarely, herpes infection during pregnancy can lead to serious complications in the mother, including severe liver damage and possibly death.
If a pregnant woman has had genital herpes in the past, there are medications that she can take to reduce the chance that she will have an outbreak, which also reduces the risk to her fetus.If a woman has active herpes sores when she goes into labor, the infant can be delivered by cesarean section to reduce the chance that the infant will come in contact with the virus.
If a woman is infected with hepatitis B virus (HBV) during pregnancy, the virus could infect her fetus. The likelihood of transmission depends on when during pregnancy the mother was infected. If the mother gets the infection later in her pregnancy, the risk that the virus will infect her fetus is quite high. If the infection occurs early in pregnancy, the risk of the virus infecting the fetus is much lower. For more information about Hep B during pregnancy, visit the Centers for Disease Control and Prevention (CDC) website. In infants, HBV can be serious and can lead to chronic liver disease or liver cancer later in life. In addition, infected newborns have a very high risk of becoming carriers of HBV and can spread the infection to others.
In some cases, if a woman is exposed to HBV during pregnancy, she may be treated with a special antibody to reduce the likelihood that she will get the infection.All healthy infants should be vaccinated against HBV to give them lifelong protection.Infants born to women with evidence of ongoing HBV infection (HBV surface antigen positive) should also receive hepatitis B hyperimmune globulin as soon as possible after birth. Hepatitis C virus (HCV). CDC offers more information about HCV.
HIV/AIDS. HIV can be passed from mother to infant during pregnancy before birth, at the time of delivery, or after birth during breastfeeding.
Listeria or listeriosis (pronounced li-steer-ee-OH-sis) is a serious infection usually caused by eating food contaminated with a particular type of bacteria. Infection during pregnancy can lead to pregnancy loss, stillbirth, preterm birth, or life-threatening infection of the newborn. Listeriosis is most often associated with eating soft cheeses and raw milk, but recent outbreaks have been associated with fresh and frozen produce. Prevention recommendations include checking food labels to avoid eating unpasteurized cheese (made from raw milk) and other actions. Learn more about preventing listeria during pregnancy.
Getting rubella (sometimes called German measles) during pregnancy can cause problems with the pregnancy as well as birth defects in the infant. Health care providers recommend that women get vaccinated against rubella before they get pregnant. Learn more about rubella and pregnancy.
Syphilis may pass from an infected mother to her fetus during pregnancy. The infection has been linked to preterm birth, stillbirth, and, in some cases, death shortly after birth. Untreated infants who survive tend to develop problems in many organs, including the brain, eyes, ears, heart, skin, teeth, and bones. All pregnant women should be screened for syphilis during their first prenatal visit. Women considered to be high risk should be screened again in the third trimester.1
Toxoplasmosis (pronounced tok-soh-plaz-MOH-sis) is a disease caused by a parasite that can be present in cat feces or used cat litter. Cats get the parasite from eating small animals or birds. In humans, the disease is usually mild, but if the parasite passes from a pregnant woman to the developing fetus, it can cause intellectual disabilities, blindness, or other problems. Women who are trying to become pregnant or are pregnant can take steps to prevent exposure to the parasite, such as having someone else clean or change the cat litter box and wearing rubber gloves to handle cat litter or while gardening.
Zikais caused by a virus spread mainly by the bite of a certain type of mosquito, but it is also spread through sexual contact. Although its symptoms are usually mild, Zika infection during pregnancy can cause pregnancy loss and other pregnancy complications, as well as birth defects and other problems for the infant.
Vaccine developed by NIH scientists shows promise in Phase 1 testing.
Results from two Phase 1 clinical trials show an experimental Zika vaccine developed by government scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, is safe and induces an immune response in healthy adults. The findings will be published on Dec. 4 in TheLancet. NIAID is currently leading an international effort to evaluate the investigational vaccine in a Phase 2/2b safety and efficacy trial.
“Following early reports that Zika infection during pregnancy can lead to birth defects, NIAID scientists rapidly created one of the first investigational Zika vaccines using a DNA-based platform and began initial studies in healthy adults less than one year later,” said NIAID Director Anthony S. Fauci, M.D. “NIAID has begun Phase 2 testing of this candidate to determine if it can prevent Zika virus infection, and the promising Phase 1 data published today support its continued development.”
Investigators from NIAID’s Vaccine Research Center (VRC) and Laboratory of Viral Diseases, part of the Division of Intramural Research, developed the investigational vaccine, which includes a small, circular piece of DNA called a plasmid. Scientists inserted genes into the plasmid that encode two proteins found on the surface of the Zika virus. After the vaccine is injected into muscle, the body produces proteins that assemble into particles that mimic the Zika virus and trigger the body to mount an immune response.
NIAID developed two different plasmids for clinical testing: VRC5288 and VRC5283. The plasmids are nearly identical, but they differ in specific regions of the genes that might affect protein expression and therefore immunogenicity. In August 2016, NIAID initiated Phase 1 trials of the VRC5288 plasmid in 80 healthy volunteers aged 18 to 35 years at three sites: the NIH Clinical Center in Bethesda, Maryland; the Center for Vaccine Development at the University of Maryland School of Medicine’s Institute for Global Health in Baltimore; and Emory University in Atlanta. Participants received a 4-milligram dose via a needle and syringe injection in the arm muscle. Participants received either two or three doses of the vaccine at varying time intervals, all at least four weeks apart.
In December 2016, NIAID initiated a separate trial testing the VRC5283 plasmid. This study took place at the NIH Clinical Center and enrolled 45 healthy volunteers aged 18 to 50 years. All participants received either two or three 4-milligram doses of the vaccine at varying time intervals. Trial investigators also tested different delivery regimens to see which was the most immunogenic. Some participants received the vaccine via a needle and syringe, while others received the vaccine from a needle-free injector that pushes fluid into the arm muscle. Additionally, some participants had the total vaccine dose divided with one shot administered in each arm.
Vaccinations were safe and well-tolerated in both trials, although some participants experienced mild to moderate reactions such as tenderness, swelling and redness at the injection site.
Scientists analyzed blood samples obtained from participants four weeks after their final vaccinations. They found that 60 to 89 percent of participants generated a neutralizing antibody response to VRC5288, whereas 77 to 100 percent of participants generated a neutralizing antibody response to VRC5283. The participants who received the VRC5283 plasmid vaccine via the needle-free injector all generated a neutralizing antibody response and had the highest levels of neutralizing antibodies. In addition, participants who received the vaccine in a split-dose administered to both arms had more robust immune responses than those receiving the full dose in one arm.
NIAID investigators concluded that VRC5283 showed the most promise and advanced it into an international efficacy trial in March 2017. The trial aims to enroll at least 2,490 healthy participants aged 15 to 35 years in areas of confirmed or potential active mosquito-transmitted Zika infection in the continental United States and Puerto Rico, Central and South America. The study is further evaluating the investigational vaccine’s safety and ability to stimulate an immune response, and will attempt to determine if it can prevent disease caused by Zika infection. For more information about the Phase 1 and Phase 2 trials, visit ClinicalTrials.gov using identifiers NCT02840487(link is external), NCT02996461 and NCT03110770.
NIAID conducts and supports research — at NIH, throughout the United States, and worldwide — to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.
About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.