Following a peak in the summer of 2022, new infections in the mpox clade IIb outbreak have decreased, due in part to the rapid availability and uptake of vaccines and other preventive measures. However, mpox remains a health threat, and no treatment has been proven safe and effective for people experiencing mpox disease.

The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, launched the STOMP trial to determine whether the antiviral drug tecovirimat can safely and effectively treat mpox. Tecovirimat, also known as TPOXX, was initially developed and approved by the Food and Drug Administration to treat smallpox—a species of virus closely related to mpox—but the drug’s safety and efficacy as an mpox treatment has not been established. The STOMP trial is a phase 3 study that aims to enroll about 500 people—a process that may require considerable time while mpox burden is low in study countries. NIAID continues to prioritize this study even while case counts are low.

VIDEO: Cyrus Javan of NIAID’s Division of AIDS explains the importance of the STOMP trial (audio description version here):

The STOMP trial was designed to be as inclusive as possible to ensure study results provide information on how tecovirimat works in the diverse populations affected by mpox. The trial is enrolling adults and children of all races and sexes, people with HIV, and pregnant and lactating people across 60 sites in the United States and Mexico, with an option for remote enrollment from other U.S. locations. More sites are expected to open in East Asia and South America.

The mpox virus has been endemic—occurring regularly—in west, central and east Africa since the first case of human mpox disease was identified in 1970. Mpox can cause flu-like symptoms and painful blisters or sores on the skin. People who acquire mpox tend to clear the infection on their own, but the virus can cause serious disease in children, pregnant people, and other people with compromised immune systems, including individuals with advanced HIV disease. Rare but serious complications of mpox include dehydration, bacterial infections, pneumonia, brain inflammation, sepsis, eye infections and death.

Completing the STOMP trial is essential, not only to evaluate a therapeutic option for the current mpox outbreak, but also to guide preparation for future outbreaks and provide evidence that could inform medical practice in historically endemic countries. The STOMP trial is sponsored by NIAID and led by the NIAID-funded Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections (ACTG).

Beyond STOMP, NIAID is co-sponsoring the PALM007 trial of tecovirimat as treatment for clade I mpox in the Democratic Republic of the Congo (DRC) with the DRC’s National Institute of Biomedical Research. PALM007 is actively enrolling. In addition, NIAID is sponsoring an immunogenicity study of the JYNNEOS preventive vaccine, which has completed enrollment and is expected to report initial results in 2024. More information about these studies, including enrollment in STOMP and PALM007, is available here:

STOMP tecovirimat treatment study 
PALM007 tecovirimat treatment study
JYNNEOS vaccine study

Promising Experimental Vaccine for Tick-borne Kyasanur Forest Disease Virus 

With pathogen-carrying ticks expanding their territories in many parts of the world, a NIAID research group has likewise expanded its vaccine research to two typically rare pathogens with potential for public health importance. The results appear promising.

Few people have heard of Kyasanur Forest disease (KFD) or Alkhurma hemorrhagic fever (AHF), but the closely related viral diseases are, respectively, on the minds of people in India and Saudi Arabia. Both are flaviviruses, part of the same family as Yellow Fever and Dengue.

KFD is mainly spread by Hemaphysalis hard ticks. AHF virus, which is a variant of KFD virus, is spread by hard ticks (Hyalomma dromedary) and soft ticks (Ornithodoros savignyi). Both viruses are hemorrhagic fever viruses, meaning they can cause internal and external bleeding, organ failure, brain inflammation and death. A vaccine exists in India for KFD, but it requires multiple doses, elicits a short duration of protection, and its effectiveness is in question.

In a new study published Sept. 6 in Science Advances, researchers from NIAID’s Rocky Mountain Laboratories in Hamilton, Montana, describe how they used genetically engineered vesicular stomatitis virus (VSV) as the platform to develop a single-dose KFD vaccine that was safe and protective in mice and pigtail macaques, and is ready for clinical trials. They also showed that the same vaccine, known as VSV-KFDV, generated cross-neutralizing immune responses against AHF, results that need confirmation through efficacy testing in animal models.

VSV, an animal virus that primarily affects cattle, was used to create the world’s first approved vaccine (2019) against Ebola virus. VSV now has been successfully tested as an experimental vaccine that has generated protective immunity against more than a dozen different viral infectious diseases. Scientists use VSV to deliver targeted proteins from a viral pathogen of interest – such as KFD virus – to a host. The host then generates an immune response that provides protection should the host be infected with that viral pathogen.

According to the Centers for Disease Control and Prevention, KFD virus was first identified in 1957 from a sick monkey in the Kyasanur Forest in India. Since then, about 500 human cases have been reported each year, with fatality rates ranging from 3% to 5%. KFD has historically been limited to a specific part of India, but KFD virus has now expanded to new parts of India.

Alkhurma hemorrhagic fever virus was discovered in 1995 in a patient with bleeding and fever after slaughtering a sheep in Saudi Arabia, according to the World Health Organization. Little is known about the virus; a study published in 2022 states that 604 cases were reported in Saudi Arabia from 1995 to 2020.

References:
B Bhatia et al. Single dose VSV-based vaccine protects against Kyasanur Forest Disease in nonhuman primates. Science Advances DOI: 10.1126/sciadv.adj1428 (2023).

B Bhatia et al. A live-attenuated viral vector vaccine protects mice against lethal challenge with Kyasanur Forest disease virus. NPJ Vaccines (2021).
 

NIAID’s VRC, S. Africa’s Afrigen Kick Off Vaccine-Sharing Efforts
Training Aimed at Making mRNA Technology Available Globally 

A team of vaccine production experts from South Africa recently finished training in Maryland as part of a global mRNA vaccine collaboration. The experts are working with scientists at NIAID’s Vaccine Research Center (VRC) to produce vaccines against a list of troubling infectious diseases.

The mRNA vaccine platform, which became commonly used during the COVID-19 pandemic, works by delivering a piece of genetic material to cells that instructs the body to make a protein fragment resembling one from a target pathogen (such as a virus). The immune system then recognizes and remembers the fragment, enabling it to mount a strong response if the body is exposed to that pathogen. The mRNA vaccine production process involves inserting the selected virus protein gene into a plasmid (a circular piece of DNA), the production of which was the topic of the visit from the South African scientists.

The seven-member team from Afrigen Biologics and Vaccines, a biotechnology company based in Cape Town, South Africa, arrived on July 21 for two weeks of collaboration and learning with VRC scientists. They focused on vaccine manufacturing at the VRC’s Vaccine Clinical Materials Program in Frederick, Maryland. Specific aspects included topics such as: inoculum growth, nutrient feeding, quality control, and other steps needed to make an mRNA vaccine. The Afrigen team also met with VRC leadership, including the recently appointed VRC Director, Dr. Ted Pierson. 

The visit represented a significant milestone for an ongoing research collaboration established in March 2022 between NIAID and Afrigen. Their objective is to share knowledge, expertise, and data to expedite mRNA vaccine production globally. As part of the collaboration, NIAID – specifically scientists at the VRC – are making plasmid DNA that will be used for Afrigen’s in vitro transcription process. Additionally, the VRC is providing technology transfer and training on plasmid DNA manufacturing, which the Afrigen group observed during the visit. In turn, Afrigen is sharing knowledge and expertise with NIAID scientists about the in vitro transcription and lipid nanoparticle formulation processes. The mutually beneficial scientific collaboration will advance each institution’s work toward establishing mRNA vaccine production capabilities to support their respective missions.

The World Health Organization, the COVAX Vaccine Manufacturing Taskforce, and the Medicines Patent Pool established a formal agreement in July 2021 to build capacity in low- and middle-income countries to make mRNA vaccines, now known as the mRNA technology transfer programme. Afrigen was chosen as a center of excellence and training, or “technology transfer hub,” as part of the mRNA technology transfer programme. The hub is designed to improve the health and security of member nations by creating sustainable, locally owned mRNA vaccine manufacturing in those nations. Because mRNA vaccines can be cheaper to produce, quickly developed in response to outbreaks, and easily modified when new variants of pathogens emerge, the ability to produce these vaccines in low- and middle-income nations will contribute significantly to global health security.

Afrigen is working to establish mRNA vaccine production technology—initially for a COVID-19 vaccine candidate—and will work with local partners to conduct research to evaluate the vaccines, along with manufacturing the vaccines at scale. The eventual goal is to be able to share this established process with manufacturers across multiple countries. 

Though the effort began with COVID-19 in mind, the scientists are mutually hoping to use the mRNA vaccine platform to develop and test vaccines against an array of infectious diseases found globally, such as HIV, tuberculosis, malaria, influenza, cancer-associated viruses and more.

Afrigen scientists spent time getting to know colleagues at the Vaccine Research Center’s Vaccine Production Program (VPP) and Vaccine Clinical Materials Program (VCMP), including during a meet-and-greet with VRC leadership and staff at the VCMP pilot plant in Frederick, Maryland.

Credit: NIAID

Viral hepatitis is an inflammatory liver disease caused by infection with any of the known hepatitis viruses—A, B, C, D, and E. Most of the global viral hepatitis burden is from hepatitis B and C, which affect 354 million people and result in 1.1 million deaths annually. The Centers for Disease Control and Prevention estimates that in 2020 there were 14,000 and 50,300 new acute infections of hepatitis B and C in the United States, respectively, while at least 880,000 people in the country were living with chronic (long-term) hepatitis B and 2.4 million people had chronic hepatitis C. About half of those with viral hepatitis are unaware of their infection. Chronic and persistent inflammation from the disease can lead to liver failure, cirrhosis, or liver cancer. Viral hepatitis affects all ages and there are pronounced inequities in disease outcomes in the United States. Hepatitis B and C disproportionately affect people living with HIV, and HIV increases the rate of complications and death in people with viral hepatitis.

On this World Hepatitis Day, the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, shares a snapshot of its investments in basic (laboratory), preclinical (laboratory/animal), and clinical (human) research to improve screening, prevention and treatment for hepatitis B and C. Scientists in the Hepatic Pathogenesis and Structural Virology sections of NIAID’s Laboratory of Infectious Diseases conduct basic and translational research to better understand hepatitis B and C disease progression, clarify the role of hepatitis viruses in liver cancer, and inform discovery of new vaccines, medicine and technologies. Both NIAID’s Division of AIDS (DAIDS) and the Division of Microbiology and Infectious Disease (DMID) support scientific programs focused on hepatitis B and C research and curative strategies, reflecting the widespread impact of viral hepatitis and the urgent need for safe and effective interventions.

Finding a hepatitis B cure

Hepatitis B continues to cause disease and death even though a highly effective preventive vaccine has been available for decades. Some people with acute hepatitis B can naturally clear the infection. In others, chronic HBV requires lifelong treatment to suppress the virus. More research is need to identify novel therapeutic options and strategies to minimize the treatment burden and, ideally, identify a cure for hepatitis B. NIAID is supporting research on a variety of basic, translational and therapeutic science concepts designed to cure hepatitis B, including in people with HIV. DMID recently announced an initiative to develop new antiviral drugs that can eliminate hepatitis B genetic material from infected cells, and DAIDS is complementing that work with clinical studies of therapeutic agents and vaccines that will include evaluation of their safety and efficacy in people living with HIV.

Streamlining the hepatitis C response

In 2011, direct-acting antivirals (DAA) revolutionized hepatitis C therapy and have since been observed to cure 95% of cases. Despite DAA availability for more than a decade, only one in three people in the United States diagnosed with hepatitis C receive curative treatment. These circumstances underscore the importance of increasing access to and convenience of diagnosis and treatment, as well as the need for a preventive vaccine. Developing a hepatitis C vaccine is challenging because of the genetic diversity of hepatitis C circulating in the population, necessitating broadly reactive vaccine technology. DMID awarded multiple grants to advance new hepatitis C vaccine designs in 2021. To better enable people to know their hepatitis C status, NIAID and other NIH institutes are supporting discovery of improved point-of-care hepatitis C testing that could be used in community and healthcare settings alike, and eliminate the need to wait for laboratory-based diagnostics. They are also supporting development of self-testing technology that people can use to screen themselves. DAIDS will soon launch an initiative to develop long-acting DAAs that could reduce the number of doses required for a full course of therapy. A recent NIAID-supported study showed even with an existing 84-tablet DAA regimen, most people with hepatitis C experienced favorable treatment outcomes without in-person healthcare visits for the duration of treatment. These innovations in diagnostics and treatment strategies aim to enable a “single-encounter cure” wherein a person could learn their hepatitis C status and collect their treatment in one healthcare visit.

These research priorities are among the current efforts in NIAID’s 60-year pursuit of scientific advances to improve the health outcomes of people with viral hepatitis. For more information on US government research to help eliminate viral hepatitis, please visit:

• NIAID Diseases & Conditions: Hepatitis
• Trans-NIH Strategic Plan to Cure Hepatitis B
• Health and Human Services Viral Hepatitis National Strategic Plan

This blog is cross-posted from HIV.gov. 

On Tuesday at the International AIDS Society’s 12th Conference on HIV Science (IAS 2023), HIV.gov continued our conversations about research highlights, including a focus on the latest about HIV vaccines. We also heard an update from the NIH Office of AIDS Research.

NIH’s Carl Dieffenbach, Ph.D., Director of the Division of AIDS at the National Institute of Allergy and Infectious Diseases (NIAID), spoke with Louis Shackelford, M.P.H., about HIV vaccine studies being discussed at IAS 2023 and potential roles for broadly neutralizing antibodies (or bNAbs). Louis is the Acting Director for External Relations at the NIH-supported HIV Vaccine Trials Network (HVTN) and COVID-19 Prevention Network. Noting it is an exciting time in HIV vaccine research, Carl explained that scientists are exploring how to take what we have learned about bNAbs, which prevented acquisition of some HIV strains, and turn that into an HIV vaccine. In addition, Carl and Louis discussed how bNAbs are being studied for use in HIV treatment and even, possibly, a cure. View their conversation below:

Bill Kapogiannis, M.D., Acting Director of NIH’s Office of AIDS Research (OAR), spoke with Catey Laube, Section Chief for HIV, STIs, Allergy, Immunology, and Transplantation in NIAID’s Office of Communications and Government Relations. OAR coordinates the scientific, budgetary, legislative, and policy components of HIV/AIDS research across NIH’s institutes and centers. Bill discussed the importance of the results from the NIH-supported REPRIEVE trial presented yesterday at the conference. The global study found that statins, a class of cholesterol-lowering medications, may offset the elevated risk of cardiovascular disease experienced by people with HIV by more than a third, potentially preventing one in five major cardiovascular events (e.g., heart attack or stroke) or premature deaths in this population. He noted that these important findings have implications for clinical guidelines for the care of people with HIV. Bill also observed that the findings are relevant to two of OAR’s signature programs: HIV and Aging, since the study population was people with HIV ages 40-75, and HIV and Women, since the results were equally applicable to women. View their conversation below:

IAS 2023, convening in Brisbane, Australia, features the latest advances in basic, clinical, and operational HIV research and seeks to move science into policy and practice. The conference features seven plenary sessions, more than 60 symposia and oral abstract sessions, hundreds of poster sessions, and many satellite sessions featuring highly diverse and cutting-edge research. Many of the studies that are being presented have been conducted by or funded by federal partners, including NIH, CDC, PEPFAR, DoD, and others.

As is the custom in Australia, HIV.gov acknowledges the Jagera and Turrbal people as the Traditional Custodians of Meanjin (Brisbane), the land on which IAS 2023 is taking place. We pay our respects to Jagera and Turrbal elders past, present, and emerging.

Follow all of our conversations from IAS 2023 this week here on the blog as well as on on HIV.gov’s Facebook, Instagram, and Twitter, and on the LinkedIn account of the HHS Office of Infectious Disease and HIV/AIDS Policy.