In 1796, British physician Edward Jenner invented the world's first vaccine. He injected a smallpox patient with a virus biologically close to smallpox, and the patient recovered!
The same procedure of administering a weak version of the virus itself to humans has been used to develop almost all vaccinations against viruses over the last 200 years.
Two Covid-19 vaccines based on mRNA technology – one developed by Pfizer in collaboration with BioNTech and the other by Moderna – have helped humanity fight and win against the coronavirus pandemic.
Unlike traditional vaccines, using viruses against viruses, messenger ribonucleic acid (mRNA) technology transforms the human body into a virus-zapping vaccine factory, teaching cells how to make a protein that triggers an immune response against viruses.
mRNA makes its way into cells within a protective bubble. Our cells then read it as a blueprint to build proteins that match up with parts of the pathogen called antigens. The body's defence mechanisms respond to these foreign antigens as if they were invaders, sending out antibodies and T-cells to neutralise them and preparing the immune system for future attacks. Because of this, our immune system may be primed to respond appropriately if and when the real virus appears, mounting an effective defence.
Researchers have spent years developing technologies to make mRNA work in the real world. For Stéphane Bancel, CEO of Moderna, the Covid vaccination is only the beginning. He's long claimed that mRNA will usher in a revolution in treating everything from heart disease to cancer to rare genetic conditions. Some breakthroughs have already been made.
HIV – Human Immunodeficiency Virus
For over four decades, scientists have gone the whole nine yards to find an effective vaccine for HIV. Though many HIV vaccine candidates have been developed since the late 1980s, none have been proven effective.
The HIV vaccine looks far more challenging than the Covid vaccine. Vaccines are developed using the virus's recognised antigens that trigger the body's immunological reaction to protect against the virus. Identifying this antigen is the primary difficulty in the case of HIV.
The recent finding of neutralising antigens, however, has renewed scientists' hope. The World Health Organisation (WHO) announced the opening of the first mRNA centre in Africa, dedicated to developing and producing vaccines using the new technology.
In addition, Moderna is developing an HIV vaccine. To assess the safety and immunogenicity of the mRNA HIV vaccine antigen and to fortify regional scientific expertise, the company and the International AIDS Vaccine Initiative initiated phase one trials in the United States, Rwanda, and South Africa in May 2022.
Executive Director of Moderna, Brett Leav is in charge of the company's public health vaccines research. He is presently managing the development of the HIV vaccine, having previously managed the Moderna mRNA Covid-19 vaccine trial program. If the current studies are successful, according to Leav, Moderna will go on with efficacy trials in patients at risk of contracting HIV.
The co-founders of the German company BioNTech, Professors Ugur Sahin and Ozlem Tureci have long been experimenting with mRNA technology to cure cancer. After developing Covid vaccine, they are now eying new treatments for bowel cancer, melanoma, and other forms of tumours.
BioNTech has several cancer trials underway. When cells become cancerous, they mutate our proteins in a way that they don't naturally appear in our body, making cancer stand out as unique to the immune system relative to other cells. So we can use mRNA to teach our body what these tumour-associated antigens look like and potentially leverage our own immune system to help fight cancer.
There are only two effective vaccines against Ebola – Ervebo and Zabdeno/Mvabea. However, the vaccinations only protect against the Zaire ebolavirus strain. There are now no vaccinations available to combat the Sudan ebolavirus, which is responsible for the current outbreak in Uganda, which has caused 53 deaths so far.
Both available vaccines against Zaire ebolavirus rely on injecting another inferior active virus, limiting their applicability. Due to the potential for undesirable side effects, Ervebo is generally reserved for usage by adults over the age of 18.
Alexander Bukreyev, a Texas-based Professor of Microbiology and Immunology, argues that although Johnson & Johnson's regimen may be delivered to adults, it must be administered in two doses, eight weeks apart, which is not ideal during an epidemic.
A vaccinologist at the University of Pennsylvania, Norbert Pardi, who specialises in mRNA technology, claims that mRNA vaccines might solve some of these problems.
To induce protection against various filoviruses simultaneously, it is simple to incorporate different strands of mRNA or to modify the proteins that the mRNA encodes if a new species crops up.
To top it all off, Pardi notes that more than five billion individuals have already been vaccinated with an mRNA vaccine, providing "real-life proof" of the safety and efficacy of such a vaccination against Covid-19.
Herpes simplex virus 2 (HSV-2) is the most prevalent sexually transmitted disease (STD). Apart from being a non-curable condition, it can invite other infections, such as HIV.
It can also be lethal to infants and foetuses of a woman infected during pregnancy. Another risk associated with HSV-2 is that it is often misdiagnosed. Some of these can be dealt with with the development of mRNA technology.
Dr Harvey Friedman and Dr Drew Weissman, with their coworkers at the University of Pennsylvania, are creating an mRNA HSV-2 vaccine to combat the wide range of adverse effects caused by HSV-2.
A study of their mRNA herpes vaccine in mice conducted before the Covid-19 pandemic indicated that practically all vaccinated mice that were later exposed to HSV-2 exhibited sterilising immunity, meaning that no sign of the disease was found in the body after the exposure.
The potential efficacy of this mRNA herpes vaccine stems from its ability to activate antibodies to three distinct HSV-2 proteins readily. According to Friedman, "One antibody inhibits the herpes virus from entering cells, while two others stop the virus from basically shutting off usual protective immune-system processes.
Fighting Flu or Replacing Seasonal Flu Vaccination
Seasonal flu is a persistent source of risk for contracting an infectious disease, says Penn microbiology professor Scott Hensley. Animal-to-human influenza transmission can even cause pandemics.
Hensley has been developing flu vaccines for over a decade. "Influenza viruses change constantly," he says, "we need new vaccines that elicit immunity against diverse viral strains and updated vaccine technologies to keep up with fast-moving viruses."
According to Hensley, mRNA technology is the solution. "These vaccines elicit high levels of antibodies that recognise antigenically diverse viral strains and the vaccines themselves can be updated easily."
Pfizer is set to conduct a phase-three efficacy study with 25,000 adults for an influenza vaccine based on mRNA.
Future Covid Variants
The pandemic phase for Covid-19 is ending in most places. However, the hit of another surge will not be surprising. Hence, the mRNA Covid-19 vaccine, which can be adjusted to fight new variants, remains valuable. Weissman's lab at Penn is developing new formulae for coronaviruses and Covid-19 variations.
On the heels of successful Covid-19 mRNA vaccines, the technology is poised to revolutionise the fight against these and many other diseases. Despite being a scourge for humanity, Covid-19 seems like a boon or a blessing in disguise for the vaccine industry.