Breaking News
February 22, 2019 - AbbVie Announces New Drug Application Accepted for Priority Review by FDA for Upadacitinib for Treatment of Moderate to Severe Rheumatoid Arthritis
February 22, 2019 - Nature versus nurture and addiction
February 22, 2019 - New website connects researchers with data experts, resources | News Center
February 22, 2019 - Today’s Concerns About Drug Prices Echo The Past
February 22, 2019 - CT and Doppler equipment have low accuracy in detecting cerebral vasospasm and ischemia
February 22, 2019 - Study finds out similarity in function between healthy retina cell and tumor cell
February 22, 2019 - CWRU awarded NIH grant to identify effective treatments for intimate partner violence
February 22, 2019 - Oncotype DX Not Cost-Effective for Low-Risk Breast Cancer
February 22, 2019 - Scientists discover new type of immune cells that are essential for forming heart valves
February 22, 2019 - Talk About Déjà Vu: Senators Set To Re-Enact Drug Price Hearing Of 60 Years Ago
February 22, 2019 - Genetic defect linked to pediatric liver disease identified
February 22, 2019 - New cellular atlas could provide a deeper insight into blinding diseases
February 22, 2019 - Growing number of cancer survivors, fewer providers point to challenge in meeting care needs
February 22, 2019 - Innovative compound offers a new therapeutic approach to treat multiple sclerosis
February 22, 2019 - $1.5 million grant to develop opioid treatment program for jail detainees
February 22, 2019 - FDA’s new proposed rule would update regulatory requirements for sunscreen products in the U.S
February 22, 2019 - Most Hip, Knee Replacements Last Decades, Study Finds
February 22, 2019 - Wellness problems prevalent among ob-gyn residents
February 22, 2019 - In the Spotlight: “The world is your oyster in geriatrics”
February 22, 2019 - Successful testing of multi-organ “human-on-a-chip” could replace animals as test subjects
February 22, 2019 - Analysis of cervical precancer shows decline in two strains of HPV
February 22, 2019 - Sugary stent eases suturing of blood vessels
February 22, 2019 - From surgery to psychiatry: A medical student reevaluates his motivations
February 22, 2019 - Is New App From Feds Your Answer To Navigating Medicare Coverage? Yes And No
February 22, 2019 - New pacemakers powered by heartbeats could reduce need for surgery
February 22, 2019 - The United States records highest drug overdose death rates
February 22, 2019 - Phase 1 data reinforce safety profile of new drug for treating Duchenne muscular dystrophy
February 22, 2019 - Vitamin D supplementation less effective in the presence of obesity, shows study
February 22, 2019 - CPRIT awards nearly $20 million to The University of Texas MD Anderson Cancer Center
February 22, 2019 - Sarepta Announces FDA Acceptance of Golodirsen (SRP-4053) New Drug Application for Patients with Duchenne Muscular Dystrophy Amenable to Skipping Exon 53
February 22, 2019 - An institutional effort to reduce the amount of opioids prescribed following lumbar surgery
February 22, 2019 - Family-history-based models perform better than non-family-history based models
February 22, 2019 - Failure to take statins leads to higher mortality rates | News Center
February 22, 2019 - New study explains why some patients report phantom sensations after limb amputation
February 22, 2019 - First motor-controlled heart valves implanted by Mainz University Medical Center
February 22, 2019 - Novel preclinical model mimics persistent interneuron loss seen in preterm infants
February 22, 2019 - Global health burden of glaucoma has increased, study reveals
February 22, 2019 - A holistic approach key to minimize treatment complexity in patients with interstitial lung disease
February 22, 2019 - 1 in 10 middle-aged Chinese adults are at high risk for heart disease, finds study
February 22, 2019 - More than half a million breast cancer patient’s lives saved by improvements in treatment
February 22, 2019 - Study finds no evidence that tougher policies prevent teenage cannabis use
February 22, 2019 - New blood test detects genetic disorders in fetuses
February 22, 2019 - Lower Self-Perception Observed in Children With Amblyopia
February 22, 2019 - Up to 15 percent of children have sleep apnea, yet 90 percent go undiagnosed
February 22, 2019 - Rare pulmonary defect prompts parents’ nationwide search for answers | News Center
February 22, 2019 - Lesbian and bisexual women at greater risk of being overweight, study finds
February 22, 2019 - UQ research may explain why vitamin D is essential for brain health
February 22, 2019 - Heart Attacks Rising Among Younger Women
February 22, 2019 - How your smartphone is affecting your relationship
February 22, 2019 - Orthopaedic surgeon receives prestigious award, $10 million grant | News Center
February 22, 2019 - New sepsis test could save thousands of lives
February 22, 2019 - Cervical cancer could be eradicated by 2100
February 21, 2019 - Sustained smoking cessation can lower risk of seropositive RA
February 21, 2019 - Thousands with chronic UTIs are not receiving the treatment they need
February 21, 2019 - Are teens getting high on social media? The surprising study seeking the pot-Instagram link
February 21, 2019 - Stanford expands biobank services | News Center
February 21, 2019 - Scientists identify link between drinking contexts and early onset intoxication among adolescents
February 21, 2019 - Strong social support may reduce cardiovascular disease risk in postmenopausal women
February 21, 2019 - Rapid expansion of interventions could prevent up to 13 million cases of cervical cancer within 50 years
February 21, 2019 - Motif Bio Receives Complete Response Letter From The FDA
February 21, 2019 - Researchers map previously unknown disease in children
February 21, 2019 - A skeptical look at popular diets: Going gluten-free
February 21, 2019 - Podcast: KHN’s ‘What The Health?’ How Safe Are Your Supplements?
February 21, 2019 - Factors associated with increased risk of developing surgical site infections
February 21, 2019 - Anticipatory signals in eye movements can help measure attentive capacity, learning with greater precision
February 21, 2019 - Study explores daily exposure to indoor air pollutants
February 21, 2019 - Evening exercise does not negatively affect sleep, may also reduce hunger
February 21, 2019 - Artificial intelligence technique can be used to identify alcohol misuse in trauma setting
February 21, 2019 - Overweight, obesity in adolescence associated with increased risk of renal cancer later in life
February 21, 2019 - BGU develops new AI platform for monitoring and predicting ALS progression
February 21, 2019 - Researchers discover a new promising target to improve HIV vaccines
February 21, 2019 - Brief Anesthesia in Infancy Does Not Mar Neurodevelopment
February 21, 2019 - Gaming system helps with autism diagnosis
February 21, 2019 - Heart Disease: Six Things Women Should Know
February 21, 2019 - More States Say Doctors Must Offer Overdose Reversal Drug Along With Opioids
February 21, 2019 - Researchers explore case studies focused on industries that kill more people than employed
February 21, 2019 - Only half of GP practice buildings are fit for purpose
February 21, 2019 - Intense exercise, fasting and hormones can enhance waste-protein removal, study shows
February 21, 2019 - Scientists can monitor brain activity to predict epileptic seizures few minutes in advance
February 21, 2019 - Study quantifies hepatic and intestinal mRNA expression of Ugt isoforms in rats
Maternally acquired Zika immunity can increase dengue disease severity in mouse pups

Maternally acquired Zika immunity can increase dengue disease severity in mouse pups

image_pdfDownload PDFimage_print
Dengue and Zika are transmitted by the same mosquito species and their distribution now overlaps in many tropical regions of the world. Credit: Jenna Hambrick, La Jolla Institute for Immunology

To say that the immune system is complex is an understatement: an immune response protective in one context can turn deadly over time, as evidenced by numerous epidemiological studies on dengue infection, spanning multiple decades and countries worldwide. These studies showed that infants born to mothers who had become immune to dengue virus can develop a severe form of dengue in infancy, at a time when their maternally-acquired antibody levels begin to drop.

Based on these reports, La Jolla Institute for Immunology (LJI) investigator Sujan Shresta, Ph.D., who studies both dengue and Zika viruses, began to explore a related question, namely, whether maternal immunity to Zika virus, which is structurally and genetically similar to dengue, might trigger a severe response to dengue infection in offspring.

Her new study published in the Nov. 14, 2018, edition of Cell Host & Microbe, supports that possibility in a mouse experiment designed to simulate this scenario. This work is timely and has implications for worldwide efforts to develop vaccines to halt Zika and dengue viruses.

“In our new paper we use mice to model an epidemiological scenario going on right now,” says Shresta, an associate professor in LJI’s Center for Infectious Disease. “There are pregnant women who previously were exposed to Zika virus and whose newborns will also encounter dengue in their infancy. Maternally-acquired anti-Zika antibodies in those infants could increase severity of dengue disease.”

Dengue and Zika viruses go hand in hand. Both are mosquito-borne members of same flavivirus family that are endemic to overlapping subtropical and tropical regions. The dire consequences of Zika infection are well-known: women who contract the virus in pregnancy can give birth to babies with catastrophic microencephaly. By contrast, dengue infection grabs fewer headlines, as its flu-like symptoms are usually mild. However, in rare circumstances it gives rise to a hemorrhagic form called Severe Dengue, which can be fatal.

It is this severe form of dengue infection that has emerged in new studies. Shresta’s team first collected mouse pups born to Zika virus-immune mothers at a time when the newborns still had maternally-derived anti-Zika antibodies in their blood. Then when pups were about a month old and their maternally-derived Zika immunity was beginning to wane, the group infected the mouse pups with dengue virus. Those mice developed the severe form of dengue disease and all succumbed. By contrast, mouse pups born to mothers with no prior immunity to Zika virus got sick when infected with dengue, but still, they survived.

Adverse effects of decreasing Zika antibody levels were specific to an encounter with dengue: when month-old pups of Zika-immune mothers where challenged with Zika rather than dengue virus in a reciprocal experiment, the pups were significantly protected from Zika.

Immunologists call this phenomenon, that is currently thought to be unique to flaviviruses, antibody-dependent enhancement or ADE. In ADE, antibodies that recognize and neutralize a specific flavivirus (in this case Zika) bind a structurally similar virus (say, dengue) but fail to neutralize it or there are just not enough antibodies around to fully inactivate the virus. Instead the virus-bound antibodies facilitate viral entry into certain cells, paradoxically worsen rather than block infection.

Why this occurs is enormously complex. “The cross-reacting antibodies are likely to bind the virus and allow it to enter cells,” says William Tang, a former researcher in Shresta’s lab and a co-first author of the study. “But the important point is that maternally-transferred Zika antibodies in our study were cross-reactive with dengue but not necessarily ‘cross-neutralizing.'”

This knowledge comes at a critical time in vaccine development. Although there are yet no FDA-approved anti-Zika vaccines and only one anti-dengue vaccine, most flavivirus vaccines in development work by generating antibodies to protect against one or the other virus. Given geographic co-mingling of dengue and Zika viruses, Shresta hopes the new study will inspire vaccinologists to create a single vaccine that can evade a potential ADE response by targeting both viruses.

This goal is tantalizing and seems within reach based on some of Shresta’s recent work. Earlier this year and in 2017 she published companion papers in Nature Communications and Nature Microbiology showing that mice experimentally rendered to possess dengue-reactive T cells were cross-protected against Zika infection (as were their offspring) via the activities of these anti-viral T cells.

“We also know from our previous dengue studies that immune responses evoked by T-cells can prevent pathogenic effects of antibodies, such as ADE,” says Shresta. “Our new findings show us that the optimal approach may be a pan-flavivirus vaccine capable of triggering both the T cell and B cell arms of the immune system to elicit maximal protection against both diseases.”


Explore further:
Maternal dengue immunity protects against fetal damage in mice following Zika infection

More information:
Angela M. Fowler, William W. Tang, Matthew P. Young, Anila Mamidi, Karla M. Viramontes, Melanie D. McCauley, Aaron F. Carlin, Robert Schooley, Jessica Swanstrom, Ralph S. Baric, Jennifer Govero, Michael S. Diamond, and Sujan Shresta. Maternally Acquired Zika Antibodies Enhance Dengue Disease Severity in Mice. Cell Host & Microbe (2018). DOI: 10.1016/j.chom.2018.09.015

Journal reference:
Cell Host & Microbe

Nature Communications

Nature Microbiology

Provided by:
La Jolla Institute for Immunology

Tagged with:

About author

Related Articles