It’s enough to make your stomach turn: the norovirus, also known as the “cruise ship” or “ski resort” virus, is a sick bug that seems to be lingering longer this year. The Health Security Agency has seen a huge surge in cases of norovirus in the UK from January to March – a 48% increase from what it should be at this time of year – and they predict that it may continue well into spring. Leapfrog’s founder Stephanie Drax spoke to virologist Carmen Mirabelli, a postdoctoral researcher at the Institute for Virology and Cell Biology at the University of Lübeck in Germany. Carmen and Stephanie discuss Carmen’s research into Lactoferrin’s effects on norovirus, and why it might be worth having Leapfrog in your back pocket this spring.
Stephanie: For 5 years you’ve studied viruses that infect the intestines and specifically norovirus. Can you tell us what norovirus is?
Carmen: It was first described as the “winter vomiting disease” but was only monitored in 1968 after an outbreak in a school in Ohio. The norovirus has evolved over time into 10 genogroups, with 3 that can affect humans. It lasts 2-3 days (except in immune-compromised cases), but it can cause chronic diarrhoea for children.
S: I read that as many as 200,000 children under 5 die of norovirus every year?
C: Yes. The problem is there’s no vaccine or medication because of the difficulty in replicating the virus – it is very difficult to replicate in a lab. The surge of cases now is probably because it disappeared for a while and has re-emerged recently. Norovirus also has a huge socioeconomical impact.
S: What are the symptoms and what is happening inside the body?
C: The symptoms are vomiting, feeling sick, and diarrhoea, and it can also cause a high temperature and headache. If we have it, we should not be in contact with people for 48 hours and we shouldn’t prepare food. We should disinfect everything because it’s so contagious. It’s called the “Cruise ship virus” because it’s so contagious. It has been estimated that we get it at least 5 times in our lifetime, which has raised questions about immunity to the virus.
When I worked at the University of Michigan we found that the infection of human norovirus in an immune cell type (B cell) can trigger cell activation – it could affect the immune system and long-term response – but we don’t have any studies in vivo. This means that vaccination studies may not be as effective and instead we should focus on entering the virus. We wanted to use Lactoferrin to try and treat the norovirus.
S: How did you begin the study in 2019 at the University of Michigan?
C: It was the excitement of having found the model of infection that supports the virus, so we tried to test the available compounds on the virus. We also had a collaboration with a Japanese company who are really interested in Lactoferrin and they funded our research. First, we used the surrogate of murine-norovirus (in a mouse). We knew that Lactoferrin was active against the murine-norovirus, so we wanted to experiment it against the human version. We did this in a cellular model of B cells (immortalised cells) – we pre-treated them with Lactoferrin and then added the virus. We saw that replication of the virus 2 days after infection was very reduced in the condition with Lactoferrin.
“In the study, we used no Lactoferrin, 200mg of Lactoferrin, and 600mg of Lactoferrin in micro-concentration, and found that the effect increased simultaneously with the increase in concentration”.
S: In 2020 you published a University of Michigan paper about Lactoferrin’s effects against SARS-CoV-2 (see the interview on Instagram) – how did the effects differ in this case?
C: For SARS, we saw the effect at the entry level – Lactoferrin was able to block the virus from binding to the cells. In norovirus, we didn’t find any effect of binding, but replication was still reduced. It was mostly affecting the interferon response (your body’s immune system responding to an infection). Lactoferrin creates a signal cascade to get the sentinels to attack the infection – which is Lactoferrin’s special role as an immune-modulator.
S: What other work has there been in this area?
C: There was a clinical trial with bovine Lactoferrin (from cow’s milk) for children 12-18 months who were not breast-fed. They found that it was not the incidence of norovisrus that was reduced – they still got diarrhoea – but the type of symptoms were reduced in the group with Lactoferrin. So Lactoferrin doesn’t prevent infection, but it helps you get better sooner.
S: There was also a previous study in Japan in 2020 – a randomised double-blinded placebo-controlled trial – for staff at kindergarten and nurseries who were susceptible to norovirus. The staff members were given 200mg and 600mg of Lactoferrin and they noticed an effect. They found that both doses significantly reduced the prevalence of symptoms.
C: And there are developments at the University of Michigan where they are plannng to move to an animal model using a chewable tablet against SARS-CoV-2, and also going ahead with more in vivo studies which will help move Lactoferrin forward as a compound.