The Future of Vaccines Through the Lens of COVID-19

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Neha Natu investigates how research on COVID-19 vaccines helped with research on other vaccines.

The pandemic has taken so much from everyone, but just as every struggle teaches us something, the coronavirus disease (COVID-19) has not failed to do so. As 2023 dawns, the pandemic comes close to its fourth year—finally revealing a glimmer of hope of a full stop to this struggle. More than 5.5 billion people worldwide have received a dose of a Covid-19 vaccine, equal to about 72 percent of the world population.

The topical importance of COVID-19 vaccines peaked due to the geopolitics and the high stakes involved, invoking a rat race between pharmaceutical companies. With a development time of just eighteen months, the swift development of the vaccines is a triumph of our modern global biomedical research infrastructure. However, all this research that helped to develop vaccines against COVID-19 didn’t start in 2020. 

Coronaviruses (CoVs) are a family of viruses often presented as mild colds in people, but also have shown to cause severe diseases, such as the severe acute respiratory syndrome (SARS) epidemic in China in 2002–2003 and the Middle East respiratory syndrome (MERS) on the Arabian Peninsula in 2012. For years, researchers had been paying attention to related coronaviruses and had already begun working on vaccines. This foresight is evidently reaping its benefits now. 

The ultimate goal of the global vaccine initiative was not necessarily to reach COVID zero, but rather to “tame this virus, to defang it, to remove its ability to cause serious disease, hospitalisation, and death,” as believed Amesh Adalja, a senior scholar at the Johns Hopkins Center for Health Security.  Amid the hundreds of candidate vaccines under clinical trials across the world using different molecular targets and techniques, they all are categorised under three distinct techniques. Different types of vaccines work in different ways to offer protection. Each COVID-19 vaccine trains the immune system to remember how to fight the virus by creating antibodies. All vaccines use a harmless version of a spike-like structure on the surface of the COVID-19 virus called an S-protein. Once the immune system knows how to respond to the spike protein, the immune system will be able to respond quickly to the actual virus spike protein and protect you against COVID-19.

Both the Janssen/Johnson & Johnson, and the AstraZeneca vaccine from the University of Oxford is a vector vaccine. Genetic material from the COVID-19 virus is placed inside a modified version of the virus vector, and once injected, it delivers the antibody blueprint to our cells. This controlled exposure to the viral genetic material trains your immune system to create antibodies and defensive white blood cells for a potential infection scenario. The Novavax COVID-19 vaccine is a protein subunit vaccine. Protein subunit vaccines contain fragmented S-proteins of COVID-19 and require adjuvants, an ingredient that helps create a stronger immune response in people receiving the vaccine, and the immune system to respond to that spike protein in the future. 

The Pfizer-BioNTech and the Moderna COVID-19 vaccines both use Messenger RNA (mRNA). mRNA is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene. In place of a weakened or inactivated virus, mRNA vaccines use mRNA created in a laboratory to teach our cells how to make a protein that triggers an immune response inside our bodies. Cited as a leap forward in vaccine technology, mRNA vaccines are deemed better due to its safety, efficacy and production. Unlike live-attenuated or viral vectored vaccines, mRNA is non-infectious and poses no concern for DNA integration mainly because it cannot enter the nucleus which contains DNA. Lipid nanoparticle (LNP) packaged mRNA are deployed against infectious diseases which increase cell delivery efficiency, stimulating a more effective immune response. Lastly, the low-cost and highly adaptable nature of mRNA certainly can’t be overlooked. 

Akiko Iwasaki, an immunologist at the Yale School of Medicine, confirms that “a lot went into the mRNA platform that we have today”. The basic research on DNA vaccines began at least 25 years ago, and RNA vaccines have benefited from 10–15 years of strong research, she says, some aimed at developing cancer vaccines. The approach has matured just at the right time - five years ago, the RNA technology would not have been ready. But apart from saving millions of lives in the present, this work has also led to valuable insights for future work on other vaccines.

The breakthrough of mRNA vaccines for COVID-19 has paved a path for a new frontier of mRNA vaccines with the potential to eradicate numerous diseases, including some types of cancer. Researchers at University of Pennsylvania are currently creating a vaccine for the most common sexually transmitted disease, genital herpes (HSV-2), a common nightmare for college students . The mRNA vaccine instructs the body to block the herpes virus from entering cells and thus ensure the virus does not block normal protective functions of the immune system. Another critically stigmatised disease is AIDS, which could significantly reduce in numbers through better mRNA vaccines. The Human Immunodeficiency Virus (HIV) attacks the body's immune system and, if not treated, can lead to Acquired ImmunoDeficiency Syndrome (AIDS). The vaccine could potentially teach the body to recognize and stop HIV variants prior to the attack, preventing further harm. Lastly, while the current malaria vaccine only has a 40% efficacy and requires to be administered annually, researchers at the University of Pennsylvania believe mRNA vaccines are the key to a more robust and long lasting solution. 

For over two decades, mRNA vaccines have been investigated thoroughly as cancer therapeutics with little success. Lately, the research interest in cancer vaccines has increased immensely as the power mRNA holds to produce vaccines has been unleashed due to COVID-19. The targeted antigen is part of the spike protein in the COVID-19 virus, whereas in cancer it would be a marker on the surface of tumour cells. These antigens are unique to individual tumours, representing a customised patient-specific vaccination strategy that has already shown encouraging results. Currently, mRNA vaccines are under development for solid tumour, and melanoma, prostate, ovarian, breast, and brain cancers. From a clinical viewpoint, it remains to be investigated which setting will benefit most from therapeutic cancer vaccines. 

With a development time of only a year, the COVID-19 vaccines have become a new benchmark for an efficient development timeline. With the pressure of people dying every second, the generous funding never wavered and the process was expedited. The vaccine trials have been nothing short of a miracle. The entire process of submitting grants, completing preclinical translational research, receiving ethics clearance and the convoluted steps that follow are set in place for a reason. However, this pandemic has shown how trials for new drugs could be faster and better without sacrificing patient safety. Perhaps a revolution is underway, awaiting to facilitate the new frontier of vaccines.