mRNA vaccines

Introduction

mRNA vaccines are one of many types of vaccines used to provide us with artificial active immunity. Despite having been in development for several decades, they gained traction after the use of the technology in Moderna and Pfizer-BioNTech’s COVID-19 vaccines. Following their success throughout the pandemic, clinical research into mRNA vaccines has been accelerated, with the ambition to create cancer vaccines. 

How the COVID-19 mRNA vaccine works

In the example of the COVID-19 vaccine, the genetic material that codes for the spike protein on the COVID-19 virus surface is isolated and used to create an mRNA molecule. The mRNA is then inserted into either a viral vector or a lipid nanoparticle so that once inside the body, it can enter cells. mRNA can then be translated at ribosomes to produce spike proteins, which are displayed on the cell surface membrane. Therefore, an immune response can be stimulated, producing both antibodies and memory cells, for a faster and stronger secondary immune response.¹

Using mRNA vaccines against cancer

More recently, there has been an influx in clinical trials aimed at utilising mRNA vaccines to fight cancer. Rather than preventing the development of cancer, they are aimed at helping the immune system to recognise and remove it. There have been two approaches to this, with some companies focussing on a general vaccine and others on a personalised one.

A general vaccine would contain mRNA coding for proteins found commonly in a range of cancers, stimulating an immune response against their respective antigens once they are synthesised. The two main advantages of this type of vaccine is the low cost, as well as the scope for large-scale production and distribution. Current trials involving them are targeting cancers such as advanced melanomas, prostate cancer and ovarian cancers. 

However, greater strides have been made in creating a personalised vaccine, which codes for neoantigens- proteins which are specific to an individual’s cancer. Since each cancer tends to present uniquely in different cases, it is important to identify the relevant antigens to ensure a high level of effectiveness; however this process can be expensive, costing several thousand pounds per dose. Ongoing phase two trials with personalised vaccines are targeting diseases such as melanoma and colorectal cancer.²

The image below, from BioNTech, summarises how a personalised cancer vaccine is created and subsequently stimulates an immune response:

There are numerous options for the delivery format of the mRNA vaccine, one of which is introducing mRNA into dendritic cells (DCs), in a process known as transfection, creating a cell-based cancer vaccine. Another alternative is injecting the mRNA directly into the body, without the use of a carrier. Whilst this technique is cheaper and quicker, without any protective carrier, the mRNA is prone to degradation by enzymes thus limiting their benefits. Currently, the most promising delivery method is through implementing a similar method to the COVID-19 vaccines by using lipid nanoparticles. These can be easily taken in by cells through endocytosis, followed by endosomal escape, enabling the mRNA to be translated at ribosomes and produce the desired antigen.³

Advantages and disadvantages

One of the greatest advantages of mRNA vaccines is the speed with which they can be developed, for example Moderna completed the whole process from design to manufacturing in just 7 weeks. In order to adapt the technology for other vaccines, all that would need to be changed is the mRNA base sequence to produce the desired protein. Although this makes it seem as if we could develop mRNA vaccines for every disease, it is the necessary, lengthy clinical trials which mean that very few are approved for use today.⁴

Another advantage is that such vaccines cannot be integrated into the genome, as the mRNA is broken down quickly after translation, as well as the absence of the enzyme reverse transcriptase. This reduces the risk of insertional mutagenesis (mutations in DNA caused by extra base pairs), which could otherwise have drastic effects on polypeptide synthesis and impact phenotype.⁵

However, one of the main limitations of mRNA is its lack of stability at high temperatures, and therefore the need for it to be transported in freezers. This is a major obstacle for those living in rural areas, as well as developing countries, both due to high transportation costs, as well as a lack of suitable infrastructure. Another limitation is potential long-term impacts, which are yet to be seen, due to the technology being relatively new compared to other forms of vaccines.⁴

Conclusion

Overall, the field of mRNA vaccine research is continually growing, with large strides being made towards a future where we can use it to treat a range of diseases. Although as of yet none have been approved for cancer treatment, there are several ongoing trials by a number of pharmaceutical companies, many of which are showing promising results. This technology has the potential to transform the way we tackle cancer and is definitely something to look out for in the near future.

References

1. Understanding covid-19 mrna vaccines [Internet]. Genome.gov. [cited 2023Mar11]. Available from: https://www.genome.gov/about-genomics/fact-sheets/Understanding-COVID-19-mRNA-Vaccines 
2. Sanderson K. How close are we to developing an mrna cancer vaccine? [Internet]. The Pharmaceutical Journal. 2022 [cited 2023Mar11]. Available from: https://pharmaceutical-journal.com/article/feature/how-close-are-we-to-developing-an-mrna-cancer-vaccine 
3. Vishweshwaraiah YL, Dokholyan NV. MRNA vaccines for cancer immunotherapy. Frontiers in Immunology. 2022;13. 
4. MRNA vaccines – here’s everything you need to know [Internet]. World Economic Forum. [cited 2023Mar11]. Available from: https://www.weforum.org/agenda/2021/07/everything-you-need-to-know-about-mrna-vaccines/ 
5. Lorentzen CL, Haanen JB, Met Ö, Svane IM. Clinical advances and ongoing trials of mrna vaccines for cancer treatment. The Lancet Oncology. 2022;23(10). 

Advertisement

When is the Next Pandemic after COVID coming? Sorry, it’s already here.

Bill Gates warned us that it was coming. Five years ago, Microsoft’s co-founder and multi-billionaire warned the world about an impending global pandemic during a Ted Talk, which has now amassed over three billion views worldwide. In the talk titled “The next outbreak? We’re not ready.”, Gates discussed the lessons learnt from Western Africa’s 2014 Ebola crisis and declared that international governments were not prepared for the foreseeable pandemic that would hit them.

Sadly, Bill Gates was right. On January the 5th, 2020, the COVID-19 virus was officially declared a global healthcare level threat by the World Health Organisation and now almost two years in, we are not yet clear of this one-in-a-generation global contagion.

So, if Gates was right the first time when should expect the next pandemic?

Unfortunately, it is bad news for us……. The next pandemic is here already and unfortunately, we don’t have any vaccines or monoclonal antibody therapy to fight it. The death rates that come with it will be higher than COVID 19, and social distancing or lockdowns will only make it worse. Because this time the cause is not an infective viral disease, it’s a mental health pandemic.

And just because this pandemic is not caused by an infection, it doesn’t mean that it won’t be more devastating if we don’t deal with it in time.

What are the common mental health impacts of the COVID-19 pandemic?

Due to the COVID 19 pandemic, there has been an exponential increase in the number of mental health problems reported over the past 18 months. An investigation conducted by Statista showed that the percentage of adults living in the United States displaying symptoms of anxiety and/or depressive disorder tripled between 2019 and 2020, increasing from 11% to 42.4%.

So what does mental health got to do with a viral infection? You never hear of it this issue when it’s influenza season.

Quite simply, this COVID 19 pandemic has been longer, harder, and far more damaging than we could ever have imagined. Although whilst people like Bill Gates have said that should have been prepared for such events, even they could not have predicted the severity of this once-in-a-generation pandemic.

Similarly, the mental health effects of COVID 19 are also more profound than usual and can even affect those who don’t actually contract the virus. The devastating problem with mental illness is that, unlike other medical conditions, it does not just affect the one person, but also has a knock-on effect on those around them, especially close family members. In this regard, it is more “infectious” than the virus itself. A WHO report suggests that mental health issues play a part in the death of over 40% of individuals and those with mental health disorders tend to die 5 years earlier than those not afflicted.

From an individual standpoint, COVID can have several ways to exert its effect on mental health. Firstly, just contracting the virus can cause the patient to feel stigmatized especially if they pass it on to family or friends. The sense of harming a loved one especially if it causes the death of that person will have a devastating effect on the person’s psyche.

Secondly, if the patient develops severe symptoms of COVID, especially for those who need intensive care, they will be forced, for maybe the first time, to face their own mortality. The elation of survival can be quickly replaced with the horrors of the near-death experience, similar to those who suffer from post-traumatic stress disorder.

Finally, the COVID 19 virus can have long-lasting medical effects for those who do contract the virus. From research so far, up to 1 in 3 people who have contracted COVID described experiencing lethargy, persisting pains as well lingering neurological and cognitive symptoms such as difficulty thinking and fumbling over simple words. Whilst it appears that most eventually will “shake off” these effects, it is believed that for a small number, this may become a chronic condition. The loss of self-worth associated with this, for the individual, is incalculable.

These effects have been even worse for members of the healthcare profession. Faced with the initial unknown nature of the pandemic and the lack of adequate protective equipment, frontline medical workers have been described as “ being on their knees” in response to the crisis by media representations, with many warning us of an even worse mental health epidemic amongst the frontline healthcare workforces.

For the most part, healthcare workers are psychologically resilient professionals highly trained to deal with death and loss. But the elevated death toll, mental and physical burnout from working overtime, and the constant stress on their own safety and the people around them have undoubtedly placed healthcare workers at additional risk for developing mental health problems. The magnitude of the sacrifices made daily by these dedicated people will not be without consequences. In fact, prior to the pandemic, this group was recognized as having the highest rates of stress, mental burnout, drug and alcohol dependence and high suicide rates. Large numbers of individuals working long-term in the NHS have quit their jobs and the loss of this talent will need time and resources to replace.

From a family standpoint, COVID has created a different, but no less devastating effect on mental health. One of the most direct manifestations of this is due to the infective nature of COVID 19. Many relatives have been unable to comfort, personally care for or be able to be at the last moment of a loved one that unfortunately lost their battle with the virus. Being able to care for and say goodbye to a family member can be a great help in the grieving process. Being robbed of this “sense of closure” is likely to make the grieving process harder and further increase the mental burden on surviving family members.

Lockdown itself has caused a number of interpersonal issues. The rates of domestic violence, separations and divorce filings have skyrocketed over the past 18 months. Families who were able to co-exist happily with each other during a normal routine found themselves unable to tolerate each other when they have to be together 24/7. Physical violence both for the victim and the perpetrator can carry a high mental toll and the ensuing separation and divorce is likely to widen the psychological damage to the entire family unit, especially the children. If unresolved, these children could potentially carry the scar of this trauma into their own adult lives and perpetuate this trauma for the next generation.

With the global lockdown has come the massive global recession which has hit world economies and the financial status of everyone around the world. Many people have lost their jobs and with it their financial stability and self-esteem. It is well known that depression and unemployment go hand in hand and with millions out of a job, this has added further to the mental health burden of those affected.

So how do we deal with this?

The difficulty in tackling this mental health pandemic is the common misconception that most believe “it won’t affect me”. Most sufferers will be in denial that they have a mental health problem. But the first step in dealing with any problem is to first admit that there is one.

So, in order for any solutions put in place to be fully effective, responses from local, nationwide, and worldwide representations must be called on to collectively decide on how best we can educate the public about the current pandemic on our mental health and come up with strategies to tackle the inevitable mental health crisis coming our way. Without public education, those affected just will not recognize that they have a problem.

Given that the majority of psychological cases will be dealt with by emergency first-responders and frontline healthcare workers with relatively low experience in mental health, many cases may be missed at the patient’s first time of contact with the medical profession.

The creation of specific guidelines must be set out by health departments and governments to help all first responders and frontline healthcare workers seamlessly diagnose, care for, and treat patients with psychological illnesses. Increasing direct access to mental health care professionals and informing the public how they can do so will also help to reduce the number of those who “slip through the net”.

Healthcare workers, teachers and governments are well-positioned to support students, patients, and the general public during this trying time. Simple solutions such as offering stress management and coping methods to the public/ students at schools should be put into effect as soon as possible. Increasing the availability of walk-in appointments with a mental health specialist in schools and workplaces will also help decrease the number of undiagnosed mental illnesses and new psychological problems being developed.

Addressing the social stigma associated with such illnesses must be another first step taken by governmental bodies, influencers and people in higher positions when tackling this crisis. People suffering and living with mental health issues should stop feeling ashamed of their condition and speak out about their own experiences to inspire others to see mental health specialists if needed.

As for hospital staff and health departments, there are a number of strategies they can implement, to ensure that patients in their wards are as well-supported as possible. For example, panic-inducing news channels constantly bombarding us with statistics on death tolls and the pandemic should be turned off. The staff can instead encourage patients to engage in mindful activities such as reading, solving puzzles and non-strenuous exercise. It is important that nurses who have direct contact with patients try to understand the world from their patient’s perspectives and tailor their care accordingly.

For better or for worse, the COVID-19 pandemic has changed us, the people around us and the world around us. But as we come closer to reaching herd immunity and a possible end to the COVID 19 pandemic, it is paramount that, more than ever, we do not turn a blind eye to the mental health crisis brewing just beneath the surface.

Dealt with wrongly, the mental health pandemic could be more devastating than the COVID pandemic we are facing now.

——

Works Cited

1.  Business Insider. 2021. Mental health problems to be next pandemic after COVID-19 crisis, says study. [online] Available at: [Accessed 13 November 2021].

2.  Dias, M. and Bunn, S., 2021. Mental health impacts of the COVID-19 pandemic on adults. [online] POST. Available at: [Accessed 13 November 2021].

3.  Mind.org.uk. 2021. [online] Available at: [Accessed 13 November 2021].

4.  Governmentevents.co.uk. 2021. Flattening a Different Curve: A Blueprint for Covid-19 Recovery? – Government Events. [online] Available at: [Accessed 13 November 2021].

5.  Daily Maverick. 2021. Sponsored Content: Is Mental Health the next pandemic?. [online] Available at: [Accessed 13 November 2021]

Dying: A Moving Poem

By Parineetha Karumanchi

Published 2:10 EST, Wed December 29th, 2021

A leaden breath 

Escapes her lips

All at once

There is no forward

For the body

Married to modern medicine

It hits you all at once

Pain gathering its things, packing up, and slipping away unannounced in the middle of the night

A fanfare of epiphany surpasses 

The sky screams your name

Sanity becomes foreign 

You become consumed by your own hysterical thoughts

Velvet shrouds consume you

Your eyes shut 

And a marriage of pale, winter green, rusted gold and specks of sleepy summer skies

Are all you can see

The low, incessant rumbling of your machines mitigates

And one meek sigh is released

As if struck by a pistol shot

You squirm for one last breath

The elixir of life discharges

Your soul ceases to exist

A quiver kisses the blood

In my veins

My brittle bones

A streak of crimson tear on your cheek

And the earth embraces you.

Parineetha Karumanchi, Youth Medical Journal 2021

The Year 2020

Darkness.

Countless lives gone, families shattered. 

Silence.

Months since we’ve heard the sound of laughter.

Crying. Shaking. Coughing. Grieving.

Life can be ever so deceiving.

Behind the masks there are faces

People starving for their loved one’s embraces 

Hatred. 

Hoards of people unjustly hurt because of their color.

Division

The country is collapsing. When can we win?

Killing. Looting. Hurting. Dying

Life can be ever so deceiving.

Our dead brothers and sisters. Remember their faces?

People starving for their loved one’s embraces

Sai Datla, Youth Medical Journal 2020