We tend to just think of viruses in terms of their damaging impacts on human health and lives. The 1918 flu pandemic killed around 50 million people. Smallpox claimed 30% of those who caught it, and survivors were often scarred and blinded. More recently, we’re all too familiar with the health and economic impacts of COVID.

But viruses can also be used to benefit human health, agriculture and the environment.

Viruses are comparatively simple in structure, consisting of a piece of genetic material (RNA or DNA) enclosed in a protein coat (the capsid). Some also have an outer envelope.

Viruses get into your cells and use your cell machinery to copy themselves.
Here are six ways we’ve harnessed this for health care and pest control.

1. To correct genes

Viruses are used in some gene therapies to correct malfunctioning genes. Genes are DNA sequences that code for a particular protein required for cell function.

If we remove viral genetic material from the capsid (protein coat) we can use the space to transport a “cargo” into cells. These modified viruses are called “viral vectors”.

Viral vectors can deliver a functional gene into someone with a genetic disorder whose own gene is not working properly.

Some genetic diseases treated this way include haemophilia, sickle cell disease and beta thalassaemia.

2. Treat cancer

Viral vectors can be used to treat cancer.

Healthy people have p53, a tumour-suppressor gene. About half of cancers are associated with the loss of p53.

Replacing the damaged p53 gene using a viral vector stops the cancerous cell from replicating and tells it to suicide (apoptosis).

Viral vectors can also be used to deliver an inactive drug to a tumour, where it is then activated to kill the tumour cell.

This targeted therapy reduces the side effects otherwise seen with cytotoxic (cell-killing) drugs.

We can also use oncolytic (cancer cell-destroying) viruses to treat some types of cancer.

Tumour cells have often lost their antiviral defences. In the case of melanoma, a modified herpes simplex virus can kill rapidly dividing melanoma cells while largely leaving non-tumour cells alone.

3. Create immune responses

Viral vectors can create a protective immune response to a particular viral antigen.

One COVID vaccine uses a modified chimp adenovirus (adenoviruses cause the common cold in humans) to transport RNA coding for the SARS-CoV-2 spike protein into human cells.

The RNA is then used to make spike protein copies, which stimulate our immune cells to replicate and “remember” the spike protein.

Then, when you are exposed to SARS-CoV-2 for real, your immune system can churn out lots of antibodies and virus-killing cells very quickly to prevent or reduce the severity of infection.

4. Act as vaccines

Viruses can be modified to act directly as vaccines themselves in several ways.

We can weaken a virus (for an attenuated virus vaccine) so it doesn’t cause infection in a healthy host but can still replicate to stimulate the immune response. The chickenpox vaccine works like this.

The Salk vaccine for polio uses a whole virus that has been inactivated (so it can’t cause disease).

Others use a small part of the virus such as a capsid protein to stimulate an immune response (subunit vaccines).

An mRNA vaccine packages up viral RNA for a specific protein that will stimulate an immune response.

5. Kill bacteria

Viruses can – in limited situations in Australia – be used to treat antibiotic-resistant bacterial infections.

Bacteriophages are viruses that kill bacteria. Each type of phage usually infects a particular species of bacteria.

Unlike antibiotics – which often kill “good” bacteria along with the disease-causing ones – phage therapy leaves your normal flora (useful microbes) intact.

6. Target plant, fungal or animal pests

Viruses can be species-specific (infecting one species only) and even cell-specific (infecting one type of cell only).

This occurs because the proteins viruses use to attach to cells have a shape that binds to a specific type of cell receptor or molecule, like a specific key fits a lock.

The virus can enter the cells of all species with this receptor/molecule. For example, rabies virus can infect all mammals because we share the right receptor, and mammals have other characteristics that allow infection to occur whereas other non-mammal species don’t.

When the receptor is only found on one cell type, then the virus will infect that cell type, which may only be found in one or a limited number of species. Hepatitis B virus successfully infects liver cells primarily in humans and chimps.

We can use that property of specificity to target invasive plant species (reducing the need for chemical herbicides) and pest insects (reducing the need for chemical insecticides). Baculoviruses, for example, are used to control caterpillars.

Similarly, bacteriophages can be used to control bacterial tomato and grapevine diseases.

Other viruses reduce plant damage from fungal pests.

Myxoma virus and calicivirus reduce rabbit populations and their environmental impacts and improve agricultural production.

Just like humans can be protected against by vaccination, plants can be “immunised” against a disease-causing virus by being exposed to a milder version.

Thea van de Mortel, Professor, Nursing, School of Nursing and Midwifery, Griffith University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

More than 16,000 Australians will be diagnosed with melanoma each year. Most of these will be caught early, and can be cured by surgery.

However, for patients with advanced or metastatic melanoma, which has spread from the skin to other organs, the outlook was bleak until the advent of targeted therapies (that attack specific cancer traits) and immune therapies (that leverage the immune system). Over the past decade, these treatments have seen a significant climb in the number of advanced melanoma patients surviving for at least five years after diagnosis, from less than 10% in 2011 to around 50% in 2021.

While this is great news, there are still many melanoma patients who cannot be treated effectively with current therapies. Researchers have developed two exciting new therapies that are being evaluated in clinical trials for advanced melanoma patients. Both involve the use of immunotherapy at different times and in different ways.

The first results from these trials are now being shared publicly, offering insight into the future of melanoma treatment.

Immunotherapy before surgery

Immunotherapy works by boosting the power of a patient’s immune system to help kill cancer cells. One type of immunotherapy uses something called “immune checkpoint inhibitors”.

Immune cells carry “immune checkpoint” proteins, which control their activity. Cancer cells can interact with these checkpoints to turn off immune cells and hide from the immune system. Immune checkpoint inhibitors block this interaction and help keep the immune system activated to fight the cancer.

Results from an ongoing phase 3 trial using immune checkpoint inhibitors were recently published in the New England Journal of Medicine.

This trial used two types of immune checkpoint inhibitors: nivolumab, which blocks an immune checkpoint called PD-1, and ipilimumab, which blocks CTLA-4.

Some 423 patients (including many from Australia) were enrolled in the trial, and participants were randomly assigned to one of two groups.

The first group had surgery to remove their melanoma, and were then given immunotherapy (nivolumab) to help kill any remaining cancer cells. Giving a systemic (whole body) therapy such as immunotherapy after surgery is a standard way of treating melanoma. The second group received immunotherapy first (nivolumab plus ipilimumab) and then underwent surgery. This is a new approach to treating these cancers.

Based on previous observations, the researchers had predicted that giving patients immunotherapy while the whole tumour was still present would activate the tumour-fighting abilities of the patient’s immune system much better than giving it once the tumour had been removed.

Sure enough, 12 months after starting therapy, 83.7% of patients who received immunotherapy before surgery remained cancer-free, compared to 57.2% in the control group who received immunotherapy after surgery.

Based on these results, Australian of the year Georgina Long – who co-led the trial with Christian Blank from The Netherlands Cancer Institute – has suggested this method of immunotherapy before surgery should be considered a new standard of treatment for higher risk stage 3 melanoma. She also said a similar strategy should be evaluated for other cancers.

The promising results of this phase 3 trial suggest we might see this combination treatment being used in Australian hospitals within the next few years.

mRNA vaccines

Another emerging form of melanoma therapy is the post-surgery combination of a different checkpoint inhibitor (pembrolizumab, which blocks PD-1), with a messenger RNA vaccine (mRNA-4157).

While checkpoint inhibitors like pembrolizumab have been around for more than a decade, mRNA vaccines like mRNA-4157 are a newer phenomenon. You might be familiar with mRNA vaccines though, as the biotechnology companies Pfizer-BioNTech and Moderna released COVID vaccines based on mRNA technology.

mRNA-4157 works basically the same way – the mRNA is injected into the patient and produces antigens, which are small proteins that train the body’s immune system to attack a disease (in this case, cancer, and for COVID, the virus).

However, mRNA-4157 is unique – literally. It’s a type of personalised medicine, where the mRNA is created specifically to match a patient’s cancer. First, the patient’s tumour is genetically sequenced to figure out what antigens will best help the immune system to recognise their cancer. Then a patient-specific version of mRNA-4157 is created that produces those antigens.

The latest results of a three-year, phase 2 clinical trial which combined pembrolizumab and mRNA-4157 were announced this past week. Overall, 2.5 years after starting the trial, 74.8% of patients treated with immunotherapy combined with mRNA-4157 post-surgery remained cancer-free, compared to 55.6% of those treated with immunotherapy alone. These were patients who were suffering from high-risk, late-stage forms of melanoma, who generally have poor outcomes.

It’s worth noting these results have not yet been published in peer-reviewed journals. They’re available as company announcements, and were also presented at some cancer conferences in the United States.

Based on the results of this trial, the combination of pembrolizumab and the vaccine progressed to a phase 3 trial in 2023, with the first patients being enrolled in Australia. But the final results of this trial are not expected until 2029.

It is hoped this mRNA-based anti-cancer vaccine will blaze a trail for vaccines targeting other types of cancer, not just melanoma, particularly in combination with checkpoint inhibitors to help stimulate the immune system.

Despite these ongoing advances in melanoma treatment, the best way to fight cancer is still prevention which, in the case of melanoma, means protecting yourself from UV exposure wherever possible.

Sarah Diepstraten, Senior Research Officer, Blood Cells and Blood Cancer Division, WEHI (Walter and Eliza Hall Institute of Medical Research) and John (Eddie) La Marca, Senior Research Officer, Blood Cells and Blood Cancer, WEHI (Walter and Eliza Hall Institute of Medical Research)

This article is republished from The Conversation under a Creative Commons license. Read the original article.