Zika Virus Infection

Work on the vaccine dates back to at least 2016, when Moderna announced that BARDA was providing $8 million to finance a phase 1 toxicology study. Moderna does not plan to advance a midstage Zika vaccine without additional outside cash, despite receiving U.S. funding thus far, according to a regulatory disclosure.  The news, tucked into Moderna’s annual report released Friday, throws cold water on the most mature vaccine in Moderna’s public health pipeline. The company is also working on vaccines for mpox and Niphah under the public health umbrella, both of which are in phase 1 studies. The Flagship biotech’s Zika vaccine, mRNA-1893, is currently in a phase 2 study that’s fully enrolled some 800 patients in the mainland U.S. and Puerto Rico. The primary completion date is late July 2024, according the study’s clinical trial record.  Work on the vaccine dates back to at least 2016 when Moderna announced that the U.S. Biomedical Advanced Research and Development Authority (BARDA) was providing $8 million to finance a phase 1 toxicology study. BARDA also offered $117 million for future phase 2 and phase 3 studies, plus large-scale manufacturing.  When Moderna finalized plans for an mRNA manufacturing site in Kenya last year, CEO Stéphane Bancel specifically mentioned the potential to develop vaccines for "persistent infectious diseases like HIV and outbreak threats such as Zika and Ebola," according to a release.  Moderna's Hamilton Bennett, who serves as senior director of Vaccine Access and Partnership, mentioned the vaccine as being a key part of the company's global health portfolio in a December 2023 ESG Day. At that time, she noted that partnerships would be key to the global health portfolio.  "The value in mRNA access is that the exploratory research that our academic collaborators are conducting is taking place on a platform and a platform that is built an early development engine, an engine that can accelerate products not only into the clinic but to licensure," Bennett said. "It's this kind of collaborative model for innovative research and the type of bold approach that Moderna is willing to take in our mission to advance the greatest impact on public health." Spokespeople for BARDA and Moderna did not immediately respond to requests for comment on the decision and on how much money had been awarded thus far.  This is the latest example of Moderna reallocating resources as it tries to stave off evaporating COVID vaccine sales with near-term launches. The company recently confirmed that some employees would be laid off after reducing its COVID manufacturing investments. Executives described 2023 as a pivot year after the commercial COVID market shaped up and demand dwindled.  Now, Moderna is looking elsewhere to resuscitate revenue and investor excitement. First and foremost is the company’s respiratory syncytial virus vaccine, slated for a decision by the FDA in May. If approved, it would join the likes of GSK and Pfizer in the older adult population. Moderna also expects interim phase 3 data on its cytomegalovirus vaccine this year. A phase 3 trial is underway testing Moderna’s individualized neoantigen therapy plus Keytruda in patients with high-risk melanoma.

Scientists have developed a new approach using the Zika virus to destroy brain cancer cells and inhibit tumor growth, while sparing healthy cells. Scientists from Duke-NUS Medical School (Duke-NUS) have developed a new approach using the Zika virus to destroy brain cancer cells and inhibit tumour growth, while sparing healthy cells. Using Zika virus vaccine candidates developed at Duke-NUS, the team discovered how these strains target rapidly proliferating cells over mature cells -- making them an ideal option to target fast-growing cancerous cells in the adult brain. Their findings, published in the Journal of Translational Medicine, potentially offer a new treatment alternative for brain cancer patients who currently have a poor prognosis. Glioblastoma multiforme is the most common malignant brain cancer, with more than 300,000 patients diagnosed annually worldwide[i]. Survival rates for such patients are poor (around 15 months), mainly due to high incidence of tumour recurrence and limited treatment options. For such patients, oncolytic virotherapy -- or the use of engineered viruses to infect and kill cancer cells -- may address the current therapeutic challenges. Zika virus is one such option in early development. The Duke-NUS team used Zika virus live-attenuated vaccine (ZIKV-LAV) strains, which are "weakened" viruses with limited ability to infect healthy cells but can still grow rapidly and spread within a tumour mass. "We selected Zika virus because it naturally infects rapidly multiplying cells in the brain, allowing us to reach cancer cells that are traditionally difficult to target. Our ZIKV-LAV strains also replicate themselves in brain cancer cells, making this a living therapy that can spread and attack neighbouring diseased cells," said Dr Carla Bianca Luena Victorio, first author of the paper and Senior Research Fellow at the Cancer & Stem Cell Biology Research Programme at Duke-NUS. Dr Victorio and the team determined that ZIKV-LAV strains were highly effective in infecting cancer cells as these viruses bind to proteins that are present in high levels only in cancer cells and not in healthy cells. Upon infecting a cancer cell, these virus strains hijack the cell's resources to reproduce, ultimately killing the cell. As the cancer cell's protective membrane ruptures upon death, it releases its contents, including virus progeny that can infect and kill neighbouring cancer cells. In addition, some cellular proteins released from the infected cells can activate an immune response to further inhibit tumour growth. Through their experiments, the team observed that infection from ZIKV-LAV strains caused 65 to 90 per cent of glioblastoma multiforme tumour cells to die. While the ZIKV-LAV strains also infected 9 to 20 per cent of cells from blood vessels in the brain, the infection did not kill these healthy cells. In contrast, the original parent Zika virus strain killed up to 50 per cent of healthy brain cells. The scientists also discovered that the ZIKV-LAV strains were not able to reproduce well even when they managed to infect healthy cells. The amount of virus measured in healthy brain cells infected with ZIKV-LAV was only 0.36 to 9 times higher than before infection. In contrast, the amount of virus in brain cancer cells infected with ZIKV-LAV was 100 to a billion times higher than before infection. This further illustrates that conditions in cancer cells are significantly more conducive for virus reproduction than in normal cells. "Since the Zika virus outbreak in 2016, understandably, there has been fear about the nature of the virus and its devastating effects. Through our work, we hope to present the Zika virus in a new light by highlighting its potential to kill cancer cells. When a live virus is attenuated, such that it is safe and effective to fight infectious diseases, it can be beneficial to human health -- not just as a vaccine but also as a potent tumour-eradicating agent," said Assistant Professor Ann-Marie Chacko from Duke-NUS' Cancer & Stem Cell Biology Research Programme. She is also the senior author of the paper. The live attenuated virus strains were originally developed as a vaccine by Professor Ooi Eng Eong's group from Duke-NUS' Emerging Infectious Diseases Research Programme. As a control, the virus strains were also tested on brain neurons or nerve cells that had been cultivated from human stem cells by Assistant Professor Alfred Sun's team from the Neuroscience & Behavioural Disorders Research Programme in Duke-NUS. This provides a reliable screening tool to assess the safety and efficacy of using the virus as therapy in human cells. Asst Prof Chacko's group is improving these and other Zika virus strains to increase their potency in killing not only brain cancer cells, but other types of cancer cells as well, while making them safer for use in patients. They are also modifying the virus so it can be imaged non-invasively after it has been injected into a patient. This will allow doctors to monitor where the virus goes in the patient and how long it is functional in the tumour. To this end, the group is exploring commercialising their virus strains as both a Zika vaccine and treatment for brain cancer, and potentially other cancers, such as ovarian cancer. Professor Patrick Tan, Senior Vice-Dean for Research at Duke-NUS, said: "This is a sterling example of how different research programmes within the School come together to tap their various expertise to advance medical knowledge and improve patients' lives. The team's valuable insights may one day translate into a new treatment option to control tumour growth or even, offer a cure for cancer."

A vaccine against Zika virus is safe and effective when administered both before and during pregnancy, according to new research. A vaccine against Zika virus is safe and effective when administered both before and during pregnancy, according to new research published in npj Vaccines. The purified, inactivated Zika vaccine (ZPIV) candidate, developed by Walter Reed Army Institute of Research (WRAIR), is being evaluated in animal models at Texas Biomedical Research Institute (Texas Biomed) in collaboration with WRAIR and Trudeau Institute in New York. The vaccine candidate has previously been shown to effectively block prenatal Zika virus transmission when given to nonhuman primates prior to pregnancy. This new study goes a critical step further, studying what happens when the vaccine is administered during pregnancy. "This is a giant step forward," says Jean Patterson, Ph.D., Professor Emeritus at Texas Biomed. "We have very strong evidence that this vaccine could protect fetal health during the next Zika outbreak." Zika virus is primarily transmitted by mosquitoes. It does not typically cause serious illness in most people; the biggest threat is to pregnant women and developing fetuses. During the 2015-2016 Zika outbreak in the Americas, there was a surge in miscarriages and babies born with extremely small heads and other severe birth defects, collectively called Congenital Zika Syndrome. Zika virus continues to circulate at low levels and has been detected in 89 countries and territories to date. "Zika virus continues to infect people around the world and present a significant risk to maternal-fetal health," says Stephen J. Thomas, M.D., an inventor of the ZPIV vaccine and a study collaborator. "Because of this, advancing the development of vaccine candidates and studying different use scenarios is incredibly important." The vaccine candidate has completed Phase 1 clinical trials in humans and was well tolerated and elicited an immune response. But clinical trials usually exclude pregnant people, leaving key questions unanswered about whether vaccination during pregnancy would be safe and potent. This new study is believed to be the first to evaluate a Zika vaccine during pregnancy in nonhuman primates. Marmosets, a small nonhuman primate that typically has twins and triplets, are sensitive to Zika virus infection and closely mirror what happens in pregnant humans. Given the drastic changes that the immune system undergoes during pregnancy, the researchers were not sure if the vaccine, when given during early pregnancy, would generate a protective immune response, such as creating protective antibodies. "The antibody response when given during pregnancy was similar to the level we observed when administered before pregnancy," says In-Jeong Kim, Ph.D., a principal investigator at Trudeau Institute. "That is very exciting." The vaccine candidate prevented placental damage and sufficiently blocked transmission of Zika virus from mother to fetus. The viral load in placentas and fetuses was significantly lower in the vaccinated group versus the unvaccinated group. Growth and development of fetuses of vaccinated adult marmosets exposed to Zika virus were similar to controls not exposed to the virus. No adverse effects were detected. What remains to be studied is if protection will last throughout pregnancy and whether offspring born from vaccinated females challenged with the virus during pregnancy are free of Congenital Zika Syndrome. "We hope to garner more interest and funding to pursue those next steps," says Dr. Patterson.