The norovirus vaccine was thwarted in the final stage of clinical trials. The norovirus vaccine from U.S. pharmaceutical company Moderna was forced to halt its phase 3 clinical trial by the U.S. Food and Drug Administration (FDA) last weekend due to serious side effects. The company explained that one participant developed the rare disease Guillain-Barré syndrome. This condition is a neurological disorder where the immune system attacks the peripheral nervous system, causing nerve damage and muscle weakness.
Norovirus infects 700 million people every year, but no vaccine has yet been developed. The virus is difficult to culture, and there are many genotypes that mutate quickly, making successful vaccine development elusive. The pharmaceutical industry is attempting challenges with different methodologies than existing vaccines. Domestic companies have also set goals to develop new types of vaccines and enter clinical trials this year.
◇ 700 million infected worldwide... approved vaccines are '0'
Norovirus is a virus that causes infectious gastroenteritis in humans through contaminated food. It can survive at low temperatures of minus 20 degrees Celsius and is a major cause of food poisoning during the winter. Diarrhea, vomiting, abdominal pain, and fever are the main symptoms, and even small amounts of viral particles can cause infections regardless of age due to its high transmissibility. Vulnerable groups, such as the elderly, children, and infants, can suffer severe complications.
According to the World Health Organization (WHO), 700 million people worldwide are infected with norovirus every year, and among them, 200,000 lose their lives. Norovirus has emerged as one of the top five causes of deaths due to food poisoning. Although norovirus is spreading, there is no vaccine to prevent it. Several pharmaceutical companies have attempted to develop one, but all have ended in failure.
The companies that had garnered the most expectations were Moderna, which developed the messenger ribonucleic acid (mRNA) vaccine for COVID-19, and HilleVax, co-founded with venture capital firm Fraser Healthcare Partners by Japan's Takeda Pharmaceutical Company.
However, with the suspension of the clinical trial, Moderna's resumption is now uncertain. HilleVax had earlier decided to halt development after failing in last July's clinical trial for a norovirus vaccine involving 2,800 infants. However, it continues to develop the norovirus vaccine targeting adults.
The reason for the ongoing failures in norovirus vaccine development lies with the virus itself. To date, 48 virus genotypes have been identified, and new mutations continue to emerge due to its complex evolutionary process. Each year, various genotypes such as GII.4, GII.3, and GII.2 are detected, and recently, the GII.17 genotype has frequently been detected not only in Korea but also in Europe and the United States.
The inability to culture the virus in cells has also hindered traditional vaccine development that utilizes the virus itself. Moderna's venture into norovirus vaccine development was prompted by its success in creating a vaccine using mRNA containing genetic information instead of the virus during the COVID-19 pandemic.
◇ VLP resembling only the shell without genes as an alternative
Given that various strains of norovirus continue to emerge, a vaccine incorporating as many genotypes as possible is necessary. In this regard, the recently highlighted "virus-like particle (VLP) vaccine" is attracting attention. VLPs enter the body shaped like the virus, provoking a strong immune response. However, unlike the actual virus, they do not have a genome, Therefore, there are fewer concerns related to infection or pathogenicity compared to existing vaccines. In other words, it induces an immune response by mimicking only the virus's appearance.
VLPs can be mass-produced and can be stored and distributed at regular refrigeration (2-8 degrees Celsius), unlike recombinant proteins or mRNA vaccines that require ultra-low temperature (below -70 degrees Celsius) storage. There are already commercially available vaccines based on VLP. These include "Gardasil," an HPV vaccine by U.S. company Merck (MSD), and a hepatitis B vaccine by U.S. company Creative Biolabs.
Domestic corporations are also working on VLP-based norovirus vaccines. INTERA, a company specializing in VLP vaccine development, is receiving support from the Ministry of Health and Welfare's Vaccine Practical Technology Development Project Team to develop a trivalent norovirus vaccine based on VLP. Earlier, in December 2023, they submitted a clinical trial plan application (IND) for the development of the first norovirus vaccine in Korea to the Ministry of Food and Drug Safety, but due to the unprecedented nature of the endeavor, they collaborated with the ministry to supplement the IND over a year.
The company recently submitted supplementary documents and stated that it plans to enter phase 1 trials in the third quarter once the review by the Ministry of Food and Drug Safety is completed. CEO Choi Deok-young noted, "Our vaccine is derived from Escherichia coli, and since it purifies the protein antigen and assembles it outside the cell, the final VLP has high purity, resulting in strong efficacy and low side effects, which distinguishes it from others."
CHA Vaccine has also joined the race. They plan to develop a quadrivalent VLP vaccine that targets four norovirus genotypes. A notable feature is applying the immune enhancer "L-pampo™" to the VLP antigen made using genetic recombination technology. They also aim to enter phase 1 clinical trials this year.
A CHA Vaccine official stated, "We have secured cell lines and virus strains for large-scale production upon product approval, and we have developed the culture and purification processes," adding, "We are currently verifying the preclinical efficacy against norovirus variants and plan to establish specific clinical plans."