Southeast Asia has seen her fair share of Nipah virus outbreaks. How do we stay ahead of the enemy?
The recent use and success of messenger RNA (mRNA) vaccines in protecting against COVID-19 illness, hospitalisation, and death during the pandemic has inspired the investigation of mRNA technology in other diseases. To this end, new research is being undertaken to develop an mRNA vaccine for the Nipah virus (NiV).
A Looming Threat – What’s Known About NiV
An endemic, bat-borne disease currently with no cure or vaccine, NiV is categorised as a high-priority pathogen by the World Health Organization (WHO) as it has a staggering fatality rate that averaged 59 per cent in the Southeast Asian and Western Pacific regions between 1998 and 2018.1,2 Pteropus fruit bats infected with the virus can spread the disease to people or other animals such as pigs via contact with their bodily fluids.
Subsequent contact with the bodily fluids of infected animals or individuals, or consumption of infected food products, could result in a wider viral spread.1,3 In many countries at high risk for the virus, such as Cambodia and Bangladesh, bat excrement is commonly used as a fertiliser by farmers,4 and subsequent person-to-person spread of NiV has been regularly reported during periods of a viral outbreak.4,5 In Bangladesh and India, for instance, families and caregivers of NiV-infected patients have had the infection passed on to them through close contact with the infected patient’s bodily fluids (including nasal or respiratory droplets).5
It has been suggested that anthropogenic factors such as agricultural expansion and intensification, alongside deforestation, have played a significant role in the emergence and spread of NiV.6 A global cause for concern, climate change could also be a factor in accelerating the spread of NiV.7 Cumulatively, these phenomena are increasingly bringing humans, livestock, and wildlife together, which in turn directly increases the risk of spill-over events (i.e., when a pathogen from one species moves into another species, resulting in an outbreak).4,8 Lack of disease awareness is another cause of worry. Even in areas where outbreaks have been found to occur, some locals do not have sufficient knowledge about the disease. A survey from Cambodia, for instance, showed that 60 per cent of respondents were unaware that bats spread the virus.9
NiV – The Worrisome Details
NiV has been classified as a high-priority pathogen by several international and local health agencies, including the World Health Organization (WHO), the US Centers for Disease Control and Prevention (CDC), and the Coalition of Epidemic Preparedness Innovations (CEPI).10,11,12,13 First detected in Malaysia in 1998, NiV is currently considered endemic to Southeast Asia.3,14 It has regularly spilt over from animals to humans, and outbreaks have been recorded almost annually in some parts of Asia.15 While Australia, Bangladesh, India, and the Philippines have all experienced NiV outbreaks, there is also evidence of past NiV infections in Cambodia, Ghana, Thailand, and Madagascar.16,17
The susceptibility of humans to the virus and its capability to spread person-to-person is a key concern, particularly in today’s highly interconnected world. The ubiquitous presence of bats in many countries around the world also increases the risk of spillover cases in previously unaffected regions. Scientists have also expressed concern about the high rate of mutation observed in NiV, which poses the risk of emerging new variants that could have higher transmissibility or can better evade the body’s immune system.18
NiV infections can induce a spectrum of symptoms that range from asymptomatic to severe. While most individuals experience milder symptoms such as fever, headaches, muscle pain, vomiting, and sore throat, people with severe infections can experience potentially life-threatening symptoms such as respiratory problems and fatal encephalitis (swelling of the brain).1,3 Infected individuals are at a high risk of death and even amongst those who survive the initial infection, residual or relapse of symptoms have been observed, sometimes years after recovery.19
The lack of treatment options for NiV means that control measures are limited to prevention. Current guidance on this matter is based on previous experience with outbreaks. Routine and thorough cleaning and disinfection of farms with appropriate detergents are considered effective in preventing infection.1 However, when an outbreak is suspected, immediate quarantine of the premises is required, and farmers may be required to cull their livestock, with close supervision of burial or incineration of carcasses. These measures inflict heavy costs on the farmers.3
During the 1999 Nipah outbreak in Malaysia, farmers had to cull nearly 1,000,000 pigs to curb the spread of the disease, incurring a cost of about US$66.8 million.3 Farmers were not the only ones affected, with other industries such as livestock feed suppliers also bearing huge costs during this period. The increasing burden of NiV around the world has also prompted governments to implement interventions that seek to reduce the risk of future outbreaks. These, too, are costly endeavours.3
A vaccine or treatment would help offset the large direct and indirect medical and non-medical costs to society associated with NiV. It would also play a significant role in controlling the global spread of the virus and potentially averting a future health crisis.
Staying One Step Ahead of the Enemy
In its efforts to develop a vaccine against NiV, Moderna is leveraging its global expertise in mRNA vaccine technology development and deployment. Developed in collaboration with the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases (NIAID), Moderna’s NiV investigational vaccine candidate, mRNA-1215, targets two proteins in the virus: the G protein that is involved with the attachment of the virus to the surface of the host’s cells, and the F protein, which plays a role in the entry of the virus into the host’s cells.
The company recently announced that the first participant had been dosed as part of an open-label dose-escalation Phase I trial of its vaccine candidate (NCT05398796), which will assess the safety, tolerability, and immunogenicity of mRNA-1215 in healthy adults aged 18-60 years.20 This clinical trial is part of Moderna’s commitment to expand its portfolio to include programmes targeting priority pathogens that threaten global health.14
In a recent announcement, Moderna detailed its global public health strategy with four key initiatives that it has committed to in advancing mRNA vaccines for the prevention of infectious diseases:10
- The company will expand its global public health portfolio to 15 vaccine programmes, targeting priority pathogens such as the Chikungunya virus, dengue, and Middle East respiratory syndrome coronavirus (MERS-CoV);
- A commitment to offering researchers the use of Moderna’s mRNA technology to explore new vaccines against other emerging or neglected infectious diseases;
- Moderna is expanding its patent pledge to not enforce its patent rights in the 92 low- and middle-income countries covered by the Global Alliance for Vaccines and Immunisation (GAVI); and
- A Memorandum of Understanding with the Government of the Republic of Kenya, with the assistance of the US government, to establish the first mRNA vaccine production facility in Africa.
It’s important to note that mRNA vaccine technology is not limited to infectious diseases. It has the potential to be used in an array of therapeutic areas, including immuno-oncology, personalised cancer vaccines, rare diseases, cardiovascular diseases, and autoimmune diseases. [APBN]
About the Author
Dr. Sunny Himansu MBBS D.SM DNB is the Associate Director of Infectious Diseases at Moderna and a Programme Leader for several public health vaccines, including an ongoing Phase 1 clinical study on Nipah virus mRNA vaccine in collaboration with National Institutes of Health (NIH). He joined Moderna in 2015 and has over ten years of experience in R&D for infectious disease vaccines and monoclonal antibodies. His clinical interests include immunology and drug development for HIV, Influenza, and emerging infectious diseases.